A Phase 1/2 interventional study of Nitisinone in Albinism and Vision Loss, sponsored by National Eye Institute (NEI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-26.
Sponsored by National Eye Institute (NEI) · Phase 1/2, Interventional, and Treatment
Background:
Objectives:
Eligibility:
Design:
Objective: The primary objective of this study is to evaluate oral nitisinone as a treatment that improves ocular pigmentation in adult participants with oculocutaneous albinism, type 1B (OCA1B). Secondary objectives of this study are to determine whether the selected outcome measures are robust enough to use in a larger trial and to assess whether oral nitisinone improves visual function, skin pigmentation, and hair pigmentation in participants with OCA1B.
Study Population: Five participants with OCA1B will be enrolled initially. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study for any reason before the Month 12 visit.
Design: In this pilot, phase 1/2, single-site, prospective, open label trial, participants will receive 2 mg of oral nitisinone daily for at least one year, and they will be followed for at least 18 months. Ocular and non-ocular data will be collected at least every three months, with the first follow-up visit occurring three months after the final baseline visit. Participants will be required to have at least 8 outpatient visits at the NEI clinic over a period of 18 months. This study has a common termination date and therefore may continue for up to four years.
Outcome Measures: The primary outcome for the study is the absolute mean change in iris pigmentation on an 8-point scale at 12 months as compared to baseline. Participants left and right eyes will be analyzed. The absolute mean change in iris pigmentation for each eye on an 8-point scale at 3, 6 and 9 months compared to baseline will be assessed as secondary outcomes. Other secondary outcomes include the absolute and percent change in semi-quantitative iris pigmentation on image analysis; the absolute change in electronic visual acuity (EVA) for each eye and binocular vision; the absolute change in contrast sensitivity without glare, with medium glare, and with high glare for binocular vision; the absolute change in full-field ERG measures for each eye; and the absolute and percent change in melanin content in skin using skin reflectometry at 3, 6, 9 and 12 months as compared to baseline; Qualitative changes in hair, skin, and fundus pigmentation at 3, 6, 9 and 12 months as compared to previous visit will be assessed. The absolute and percent change in hair melanin will also be assessed at 12 months as compared to baseline. The number and severity of adverse events and the number of withdrawals will be assessed as safety outcomes.
17 studies on the registry are indexed under Albinism; 8 are open to participants now.
Browse Albinism studies →National Eye Institute (NEI) is the lead sponsor of 272 studies on the registry; 17 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
To be eligible, the following inclusion criteria must be met, when applicable.
Any female participant of childbearing potential and any male participant able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse, or must agree to practice two effective methods of while taking the investigational product and for at least two months following the last dose of investigational product. Acceptable methods of contraception include:
Participant must have OCA1B, as defined by ALL (a-d) of the following criteria:
Participant has ophthalmic signs or symptoms of albinism, including:
EXCLUSION CRITERIA:
Participant has any of the following abnormal laboratory test results:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Oral administration of nitisinone
Drug: Nitisinone
Oral dose of 2mg daily for 12 months.
Also known as: Orfadin
Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 12 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 12 months was calculated; these mean grades were then used to calculate absolute change from baseline at 12 months.
Time frame: Baseline and 12 months
Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 3 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 3 months was calculated; these mean grades were then used to calculate absolute change from baseline at 3 months.
Time frame: Baseline and 3 months
Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 6 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 6 months was calculated; these mean grades were then used to calculate absolute change from baseline at 6 months.
Time frame: Baseline and 6 months
Absolute Mean Change in Iris Pigmentation on an 8-point Iris Transillumination Scale at 9 Months as Compared to Baseline. Participants Left and Right Eyes Will be Analyzed.
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 9 months was calculated; these mean grades were then used to calculate absolute change from baseline at 9 months.
Time frame: Baseline and 9 months
Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 3 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 3 months; these mean grades were then used to calculate absolute change from baseline.
Time frame: Baseline and 3 months
Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 6 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 6 months; these mean grades were then used to calculate absolute change from baseline.
Time frame: Baseline and 6 months
Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 9 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 9 months; these mean grades were then used to calculate absolute change from baseline.
Time frame: Baseline and 9 months
Absolute Change in Semi-quantitative Iris Pigmentation for Each Eye at 12 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 12 months; these mean grades were then used to calculate absolute change from baseline.
Time frame: Baseline and 12 months
Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 3 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 3 months; these mean grades were then used to calculate percentage change from baseline.
Time frame: Baseline and 3 months
Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 6 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 6 months; these mean grades were then used to calculate percentage change from baseline.
Time frame: Baseline and 6 months
Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 9 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 9 months; these mean grades were then used to calculate percentage change from baseline.
Time frame: Baseline and 9 months
Percent Change in Semi-quantitative Iris Pigmentation for Each Eye at 12 Months as Compared to Baseline
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 12 months; these mean grades were then used to calculate percentage change from baseline.
Time frame: Baseline and 12 months
Absolute Change in Electronic Visual Acuity at 3 Months Compared to Baseline
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time frame: Baseline and 3 months
Absolute Change in Electronic Visual Acuity at 6 Months Compared to Baseline
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time frame: Baseline and 6 months
Absolute Change in Electronic Visual Acuity at 9 Months Compared to Baseline
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time frame: Baseline and 9 months
Absolute Change in Electronic Visual Acuity at 12 Months Compared to Baseline
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
Time frame: Baseline and 12 months
Absolute Change in Contrast Sensitivity Without Glare at 3 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 3 months
Absolute Change in Contrast Sensitivity Without Glare at 6 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 6 months
Absolute Change in Contrast Sensitivity Without Glare at 9 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 9 months
Absolute Change in Contrast Sensitivity Without Glare at 12 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 12 months
Absolute Change in Contrast Sensitivity With Medium Glare at 3 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 3 months
Absolute Change in Contrast Sensitivity With Medium Glare at 6 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 6 months
Absolute Change in Contrast Sensitivity With Medium Glare at 9 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 9 months
Absolute Change in Contrast Sensitivity With Medium Glare at 12 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 12 months
Absolute Change in Contrast Sensitivity With High Glare at 3 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 3 months
Absolute Change in Contrast Sensitivity With High Glare at 6 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 6 months
Absolute Change in Contrast Sensitivity With High Glare at 9 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 9 months
Absolute Change in Contrast Sensitivity With High Glare at 12 Months Compared to Baseline
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
Time frame: Baseline and 12 months
Absolute Change in Adjusted Melanin Index at 3 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 3 Months
Absolute Change in Adjusted Melanin Index at 6 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 6 Months
Absolute Change in Adjusted Melanin Index at 9 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 9 Months
Absolute Change in Adjusted Melanin Index at 12 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 12 Months
Percent Change in Adjusted Melanin Index at 3 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 3 Months
Percent Change in Adjusted Melanin Index at 6 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 6 Months
Percent Change in Adjusted Melanin Index at 9 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 9 Months
Percent Change in Adjusted Melanin Index at 12 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 12 Months
Absolute Change in Melanin Index at 3 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 3 Months
Absolute Change in Melanin Index at 6 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 6 Months
Absolute Change in Melanin Index at 9 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 9 Months
Absolute Change in Melanin Index at 12 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
Time frame: Baseline and 12 Months
Percent Change in Melanin Index at 3 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 3 Months
Percent Change in Melanin Index at 6 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 6 Months
Percent Change in Melanin Index at 9 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 9 Months
Percent Change in Melanin Index at 12 Months Compared to Baseline
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
Time frame: Baseline and 12 Months
Absolute Change in Electroretinogram (ERG) at Month 6 as Compared to Baseline.
Amplitude for the ERG parameter, Dark Adaptation (DA) Comb B, was measured at each visit. Participants left and right eye will be analyzed.
Time frame: Baseline and 6 months
Absolute Change in Electroretinogram (ERG) at Month 12 as Compared to Baseline.
Amplitude for the ERG parameter, Dark Adaptation (DA) Comb B, was measured at each visit. Participants left and right eye will be analyzed.
Time frame: Baseline and 12 months
Qualitative Change in Hair Pigmentation at 3 Months Compared to Previous Visit.
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
Time frame: Baseline and 3 months
Qualitative Change in Hair Pigmentation at 6 Months Compared to Previous Visit.
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
Time frame: 3 Months and 6 months
Qualitative Change in Hair Pigmentation at 9 Months Compared to Previous Visit.
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
Time frame: 6 Months and 9 months
Qualitative Change in Hair Pigmentation at 12 Months Compared to Previous Visit.
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
Time frame: 9 Months and 12 months
Qualitative Change in Skin Pigmentation at 3 Months Compared to Previous Visit.
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
Time frame: Baseline and 3 months
Qualitative Change in Skin Pigmentation at 6 Months Compared to Previous Visit.
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
Time frame: 3 Months and 6 months
Qualitative Change in Skin Pigmentation at 9 Months Compared to Previous Visit.
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
Time frame: 6 Months and 9 months
Qualitative Change in Skin Pigmentation at 12 Months Compared to Previous Visit.
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
Time frame: 9 Months and 12 months
Qualitative Change in Fundus Pigmentation at 3 Months Compared to Previous Visit.
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
Time frame: Baseline and 3 months
Qualitative Change in Fundus Pigmentation at 6 Months Compared to Previous Visit.
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
Time frame: 3 Months and 6 months
Qualitative Change in Fundus Pigmentation at 9 Months Compared to Previous Visit.
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
Time frame: 6 Months and 9 months
Qualitative Change in Fundus Pigmentation at 12 Months Compared to Previous Visit.
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
Time frame: 9 Months and 12 months
Absolute Change in Hair Melanin at 12 Months Compared to Baseline
Hair melanin was assessed using pyrrole-2,3,5-tricarboxylic acid (PTCA), a marker of eumelanin and 4-amino-3-hydroxyphenylalanine (4-AHP), a marker of pheomelanin.
Time frame: Baseline and 12 months
Percent Change in Hair Melanin at 12 Months Compared to Baseline
Hair melanin was assessed using pyrrole-2,3,5-tricarboxylic acid (PTCA), a marker of eumelanin and 4-amino-3-hydroxyphenylalanine (4-AHP), a marker of pheomelanin.
Time frame: Baseline and 12 months
Number of Ocular Adverse Events
Time frame: Study duration, up to 18 months
Number of Non-ocular Adverse Events
Time frame: Study duration, up to 18 months
Severity of Adverse Events
Time frame: Study duration, up to 18 months
Number of Adverse Events Related to Investigational Product (IP)
Time frame: Study duration, up to 18 months
Number of Participants Withdrawn From Investigational Product (IP) Due to Safety and Abnormal Laboratory Results
Time frame: Study duration, up to 18 months
Five participants with OCA1B will be enrolled initially. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study for any reason before the Month 12 visit.
| Milestone | Nitisinone |
|---|---|
| Started | 5 |
| Completed | 5 |
| Not completed | 0 |
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 12 months was calculated; these mean grades were then used to calculate absolute change from baseline at 12 months.
| scores on a scale | Nitisinone |
|---|---|
| OD | 1.2 ± 1.68 |
| OS | 0.9 ± 1.52 |
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 3 months was calculated; these mean grades were then used to calculate absolute change from baseline at 3 months.
| scores on a scale | Nitisinone |
|---|---|
| OD | 0.8 ± 1.04 |
| OS | 0.9 ± 1.23 |
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 6 months was calculated; these mean grades were then used to calculate absolute change from baseline at 6 months.
| scores on a scale | Nitisinone |
|---|---|
| OD | 0.6 ± 0.39 |
| OS | 0.4 ± 0.31 |
High-resolution (2544x1696) digital images of the anterior segment of both eyes were captured prior to pupil dilation using diffuse illumination and iris transillumination. An independent reviewer selected two transillumination images from each eye of each participant for each visit according to preset quality criteria. Images were coded, randomized and presented to a panel of 18 graders on a SHARP 90" HD LED TV. After instruction and a practice dataset, graders scored each image using an 8-point scale. Graders could score images with a single decimal place if they felt an image fell in between two of the standards. The iris transillumination scale ranged from 0 to 8, with lower scores reflective of greater iris pigmentation (melanin content). The mean across all graders and the two images for each participant's eye at baseline and 9 months was calculated; these mean grades were then used to calculate absolute change from baseline at 9 months.
| scores on a scale | Nitisinone |
|---|---|
| OD | 0.9 ± 1.06 |
| OS | 0.6 ± 0.60 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 3 months; these mean grades were then used to calculate absolute change from baseline.
| scores on a scale | Nitisinone |
|---|---|
| OD | 1.2 ± 1.04 |
| OS | 0.6 ± 0.82 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 6 months; these mean grades were then used to calculate absolute change from baseline.
| scores on a scale | Nitisinone |
|---|---|
| OD | 0.4 ± 0.55 |
| OS | 0.1 ± 0.22 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 9 months; these mean grades were then used to calculate absolute change from baseline.
| scores on a scale | Nitisinone |
|---|---|
| OD | 0.8 ± 0.76 |
| OS | 0.7 ± 0.84 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 12 months; these mean grades were then used to calculate absolute change from baseline.
| scores on a scale | Nitisinone |
|---|---|
| OD | 1.4 ± 1.39 |
| OS | 1.2 ± 1.15 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 3 months; these mean grades were then used to calculate percentage change from baseline.
| percentage change | Nitisinone |
|---|---|
| OD | 66.7 ± 51.37 |
| OS | 29.0 ± 41.29 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 6 months; these mean grades were then used to calculate percentage change from baseline.
| percentage change | Nitisinone |
|---|---|
| OD | 23.3 ± 32.49 |
| OS | 4.0 ± 8.94 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 9 months; these mean grades were then used to calculate percentage change from baseline.
| percentage change | Nitisinone |
|---|---|
| OD | 42.0 ± 42.66 |
| OS | 34.0 ± 42.19 |
In Adobe Photoshop 7.0 the high resolution slit lamp image was divided into 4 quadrants with vertical and horizontal lines transecting the center of the iris. Using the elliptical marquee tool, a circle, approximately 0.25 times the diameter of the iris, was drawn in the center of each quadrant. Gaussian blur with radius of 50 was applied to the area enclosed in the 4 circles. With the dropper tool, the red pigment value corresponding to the degree of iris transillumination was sampled at the center of each circle. The 4 values were averaged to yield a composite transillumination score for each subject. Quantified values were then correlated to a scale score from 1 to 8 to generate an 8-point iris transillumination scale, with lower scores reflective of greater iris pigmentation (melanin content). The mean score across the 2 images for each participant's eye was calculated at baseline and 12 months; these mean grades were then used to calculate percentage change from baseline.
| percentage change | Nitisinone |
|---|---|
| OD | 77.7 ± 91.94 |
| OS | 67.0 ± 59.75 |
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
| ETDRS letters | Nitisinone |
|---|---|
| OD | 1.8 ± 0.84 |
| OS | 6.0 ± 3.61 |
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
| ETDRS letters | Nitisinone |
|---|---|
| OD | 4.2 ± 2.17 |
| OS | 4.8 ± 3.42 |
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
| ETDRS letters | Nitisinone |
|---|---|
| OD | 2.8 ± 2.95 |
| OS | 5.6 ± 2.51 |
Visual acuity was measured using the Electronic ETDRS Visual Acuity Testing protocol. Acuity is measured as letters read using an electronic ETDRS program.
| ETDRS letters | Nitisinone |
|---|---|
| OD | 5.4 ± 3.78 |
| OS | 5.0 ± 5.70 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.6 ± 1.52 |
| Frequency 3 | 0.8 ± 0.84 |
| Frequency 6 | 0.4 ± 0.55 |
| Frequency 12 | 1.2 ± 2.17 |
| Frequency 18 | 0.6 ± 1.34 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 2.0 ± 2.83 |
| Frequency 3 | 0.2 ± 0.45 |
| Frequency 6 | 1.6 ± 1.52 |
| Frequency 12 | 2.8 ± 2.95 |
| Frequency 18 | 0.0 ± 0.00 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.8 ± 2.49 |
| Frequency 3 | 0.6 ± 0.55 |
| Frequency 6 | 1.0 ± 1.00 |
| Frequency 12 | 1.4 ± 2.19 |
| Frequency 18 | 0.0 ± 0.00 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. The minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity without glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 2.4 ± 2.51 |
| Frequency 3 | 2.0 ± 2.55 |
| Frequency 6 | 1.8 ± 1.92 |
| Frequency 12 | 1.6 ± 2.19 |
| Frequency 18 | 0.6 ± 1.34 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.4 ± 1.14 |
| Frequency 3 | 0.4 ± 0.55 |
| Frequency 6 | 3.6 ± 3.78 |
| Frequency 12 | 0.2 ± 0.45 |
| Frequency 18 | 0.6 ± 1.34 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 2.4 ± 2.88 |
| Frequency 3 | 1.4 ± 1.67 |
| Frequency 6 | 1.8 ± 1.79 |
| Frequency 12 | 0.4 ± 0.89 |
| Frequency 18 | 0.6 ± 1.34 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 2.0 ± 2.35 |
| Frequency 3 | 1.2 ± 0.84 |
| Frequency 6 | 1.0 ± 1.00 |
| Frequency 12 | 0.6 ± 1.34 |
| Frequency 18 | 0.8 ± 1.30 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with medium glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.4 ± 2.61 |
| Frequency 3 | 1.8 ± 1.79 |
| Frequency 6 | 2.6 ± 2.79 |
| Frequency 12 | 0.4 ± 0.89 |
| Frequency 18 | 1.2 ± 1.64 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 3 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.2 ± 1.10 |
| Frequency 3 | 1.8 ± 2.49 |
| Frequency 6 | 0.2 ± 0.45 |
| Frequency 12 | 0.2 ± 0.45 |
| Frequency 18 | 0.0 ± 0.00 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 6 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.0 ± 1.00 |
| Frequency 3 | 1.6 ± 1.67 |
| Frequency 6 | 1.2 ± 2.17 |
| Frequency 12 | 0.4 ± 0.55 |
| Frequency 18 | 0.0 ± 0.00 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 9 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.4 ± 0.55 |
| Frequency 3 | 0.6 ± 0.55 |
| Frequency 6 | 1.0 ± 2.24 |
| Frequency 12 | 1.6 ± 2.61 |
| Frequency 18 | 0.6 ± 1.34 |
Gratings, images with alternating light and dark bars, assess contrast sensitivity via spatial frequency and contrast. Spatial frequency (SF), the number of pairs of bars (1 light, 1 dark) imaged within a given distance of the retina, is measured as the number of cycles per degree (cpd) of visual angle, where a cycle is 1 pair of bars. Grating of high SF corresponds to narrow bars; grating of low SF corresponds to wide bars. Contrast is the intensity difference between light and dark bars. Minimum contrast required to detect a given SF is the threshold contrast. The lower the threshold contrast, higher the contrast sensitivity. Contrast sensitivity with high glare was measured at frequencies of 1.5, 3, 6, 12, 18 cpd. Absolute change from baseline to 12 months was calculated. Raw values were used for the planned descriptive analysis; logarithmic transformation was not used as formal statistical analysis was not planned and was not appropriate as a majority of the raw values were 0.
| units | Nitisinone |
|---|---|
| Frequency 1.5 | 1.6 ± 1.52 |
| Frequency 3 | 2.2 ± 2.28 |
| Frequency 6 | 2.6 ± 3.21 |
| Frequency 12 | 1.8 ± 1.79 |
| Frequency 18 | 0.0 ± 0.00 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Adjusted Melanin Index*10^-5 | Nitisinone |
|---|---|
| Forehead | 16.4 ± 14.95 |
| Inner Bicep | 4.8 ± 5.24 |
| Lower Back | 20.9 ± 18.91 |
| Inner Forearm | 10.7 ± 5.52 |
| Outer Forearm | 10.6 ± 5.60 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Adjusted Melanin Index*10^-5 | Nitisinone |
|---|---|
| Forehead | 11.8 ± 4.57 |
| Inner Bicep | 8.2 ± 6.19 |
| Lower Back | 9.3 ± 7.60 |
| Inner Forearm | 12.1 ± 10.59 |
| Outer Forearm | 12.6 ± 6.71 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Adjusted Melanin Index*10^-5 | Nitisinone |
|---|---|
| Forehead | 10.3 ± 13.41 |
| Inner Bicep | 9.4 ± 5.85 |
| Lower Back | 5.5 ± 4.12 |
| Inner Forearm | 11.6 ± 7.82 |
| Outer Forearm | 1.5 ± 0.98 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Adjusted Melanin Index*10^-5 | Nitisinone |
|---|---|
| Forehead | 8.3 ± 6.89 |
| Inner Bicep | 7.0 ± 7.74 |
| Lower Back | 4.2 ± 3.18 |
| Inner Forearm | 6.8 ± 4.20 |
| Outer Forearm | 8.6 ± 5.09 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 50.1 ± 49.48 |
| Inner Bicep | 40.1 ± 35.76 |
| Lower Back | 201.0 ± 321.19 |
| Inner Forearm | 83.3 ± 70.69 |
| Outer Forearm | 42.1 ± 22.67 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 35.4 ± 14.10 |
| Inner Bicep | 123.0 ± 113.41 |
| Lower Back | 117.4 ± 120.5 |
| Inner Forearm | 91.1 ± 116.26 |
| Outer Forearm | 67.9 ± 56.49 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 33.2 ± 44.21 |
| Inner Bicep | 94.5 ± 60.03 |
| Lower Back | 39.6 ± 42.36 |
| Inner Forearm | 81.0 ± 93.51 |
| Outer Forearm | 6.0 ± 5.86 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Apparent absorbance (AA) at a given wavelength was determined as log10 (PR of blank/PR of object) at that wavelength. Adjusted Melanin (AM) index is calculated as the slope of AA levels from 650 to 700 nm. Lower values of AM index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites: forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 24.7 ± 21.76 |
| Inner Bicep | 104.5 ± 132.61 |
| Lower Back | 32.7 ± 31.81 |
| Inner Forearm | 47.4 ± 48.10 |
| Outer Forearm | 30.5 ± 7.60 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Melanin Index | Nitisinone |
|---|---|
| Forehead | 3.8 ± 3.02 |
| Inner Bicep | 1.4 ± 0.69 |
| Lower Back | 0.6 ± 0.63 |
| Inner Forearm | 1.8 ± 1.12 |
| Outer Forearm | 4.5 ± 4.45 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Melanin Index | Nitisinone |
|---|---|
| Forehead | 2.2 ± 1.29 |
| Inner Bicep | 2.7 ± 1.68 |
| Lower Back | 3.3 ± 3.72 |
| Inner Forearm | 2.1 ± 1.43 |
| Outer Forearm | 4.4 ± 5.80 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Melanin Index | Nitisinone |
|---|---|
| Forehead | 2.4 ± 1.98 |
| Inner Bicep | 1.9 ± 1.60 |
| Lower Back | 3.2 ± 3.23 |
| Inner Forearm | 2.1 ± 1.33 |
| Outer Forearm | 2.2 ± 2.48 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Absolute change from baseline was calculated using these mean values.
| Melanin Index | Nitisinone |
|---|---|
| Forehead | 3.7 ± 3.29 |
| Inner Bicep | 2.3 ± 1.90 |
| Lower Back | 2.0 ± 1.55 |
| Inner Forearm | 2.2 ± 1.96 |
| Outer Forearm | 3.4 ± 3.38 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 15.0 ± 12.90 |
| Inner Bicep | 6.7 ± 3.50 |
| Lower Back | 2.8 ± 3.34 |
| Inner Forearm | 8.6 ± 5.84 |
| Outer Forearm | 18.9 ± 19.90 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 8.4 ± 4.62 |
| Inner Bicep | 12.7 ± 8.31 |
| Lower Back | 17.0 ± 19.52 |
| Inner Forearm | 10.2 ± 7.50 |
| Outer Forearm | 19.2 ± 24.93 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 9.2 ± 7.30 |
| Inner Bicep | 8.9 ± 7.89 |
| Lower Back | 15.8 ± 16.17 |
| Inner Forearm | 9.5 ± 6.15 |
| Outer Forearm | 8.8 ± 10.63 |
Microflash 200D is a diffuse reflectance spectrophotometer that uses a prism photodiode to provide information at 10 nm increments along the visual spectrum from 400 to 700 nm. Percent reflectance (PR) at a specific wavelength was placed into context by relating it to the reflectance of a blank at the equivalent wavelength (i.e. relating the object's reflectance to the maximum reflectance possible). Melanin (M) index was calculated as follows: Eqn 1= \[ (PR at 650nm + PR at 660nm + 0.5\*PR at 640nm + 0.5\*PR at 670nm)/3 \]/100; M index = 100\*log (1/Eqn 1) Higher values of M index correspond to higher melanin concentrations. Measurements were collected 5 times at each visit from each of the following sites:forehead, inner forearm, outer forearm, inner bicep and lower back. The mean of these five measurements was calculated at each visit. Percent change from baseline was calculated using these mean values.
| Percentage change | Nitisinone |
|---|---|
| Forehead | 14.7 ± 14.11 |
| Inner Bicep | 10.9 ± 9.43 |
| Lower Back | 10.2 ± 7.92 |
| Inner Forearm | 10.4 ± 10.19 |
| Outer Forearm | 13.3 ± 13.44 |
Amplitude for the ERG parameter, Dark Adaptation (DA) Comb B, was measured at each visit. Participants left and right eye will be analyzed.
| µV | Nitisinone |
|---|---|
| OD | 38.6 ± 27.93 |
| OS | 76.2 ± 29.06 |
Amplitude for the ERG parameter, Dark Adaptation (DA) Comb B, was measured at each visit. Participants left and right eye will be analyzed.
| µV | Nitisinone |
|---|---|
| OD | 27.8 ± 16.66 |
| OS | 85.8 ± 83.83 |
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
| Participants | Nitisinone |
|---|---|
| No change in hair pigmentation | 1 |
| Increase in hair pigmentation | 4 |
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
| Participants | Nitisinone |
|---|---|
| No change in hair pigmentation | 3 |
| Increase in hair pigmentation | 2 |
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
| Participants | Nitisinone |
|---|---|
| No change in hair pigmentation | 4 |
| Increase in hair pigmentation | 1 |
Qualitative change in hair pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
| Participants | Nitisinone |
|---|---|
| No change in hair pigmentation | 5 |
| Increase in hair pigmentation | 0 |
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
| Participants | Nitisinone |
|---|---|
| No change in skin pigmentation | 4 |
| Increase in skin pigmentation | 1 |
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
| Participants | Nitisinone |
|---|---|
| No change in skin pigmentation | 5 |
| Increase in skin pigmentation | 0 |
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
| Participants | Nitisinone |
|---|---|
| No change in skin pigmentation | 5 |
| Increase in skin pigmentation | 0 |
Qualitative change in skin pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
| Participants | Nitisinone |
|---|---|
| No change in skin pigmentation | 5 |
| Increase in skin pigmentation | 0 |
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 3 compared to previous visit.
| Participants | Nitisinone |
|---|---|
| No change in fundus pigmentation | 5 |
| Increase in fundus pigmentation | 0 |
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 6 compared to Month 3
| Participants | Nitisinone |
|---|---|
| No change in fundus pigmentation | 5 |
| Increase in fundus pigmentation | 0 |
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 9 compared to Month 6
| Participants | Nitisinone |
|---|---|
| No change in fundus pigmentation | 5 |
| Increase in fundus pigmentation | 0 |
Qualitative change in fundus pigmentation was measured as a binary endpoint (no change vs. increase) at Month 12 compared to Month 9
| Participants | Nitisinone |
|---|---|
| No change in fundus pigmentation | 5 |
| Increase in fundus pigmentation | 0 |
Hair melanin was assessed using pyrrole-2,3,5-tricarboxylic acid (PTCA), a marker of eumelanin and 4-amino-3-hydroxyphenylalanine (4-AHP), a marker of pheomelanin.
| ng/mg | Nitisinone |
|---|---|
| PTCA | 8.38 ± 5.11 |
| 4-AHP | 5.92 ± 11.68 |
Hair melanin was assessed using pyrrole-2,3,5-tricarboxylic acid (PTCA), a marker of eumelanin and 4-amino-3-hydroxyphenylalanine (4-AHP), a marker of pheomelanin.
| percentage change | Nitisinone |
|---|---|
| PTCA | 50.30 ± 45.92 |
| 4-AHP | 27.23 ± 23.22 |
| ocular adverse events | Nitisinone |
|---|---|
| Number of Ocular Adverse Events | 0 |
| non-ocular adverse events | Nitisinone |
|---|---|
| Number of Non-ocular Adverse Events | 10 |
| adverse events | Nitisinone |
|---|---|
| Mild | 9 |
| Moderate | 1 |
| adverse events related to IP | Nitisinone |
|---|---|
| Number of Adverse Events Related to Investigational Product (IP) | 0 |
| participant withdrawals | Nitisinone |
|---|---|
| Number of Participants Withdrawn From Investigational Product (IP) Due to Safety and Abnormal Laboratory Results | 0 |
Collected over Up to 18 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Nitisinone | 0/5 (0%) | 0/5 (0%) | 5/5 (100%) |
| Event | Nitisinone |
|---|---|
| AnaemiaBlood and lymphatic system disorders | 1/5 |
| PalpitationsCardiac disorders | 1/5 |
| DizzinessGeneral disorders | 1/5 |
| DyspepsiaGastrointestinal disorders | 1/5 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 1/5 |
| Gastrooesophageal reflux diseaseGastrointestinal disorders | 1/5 |
| HaemangiomaVascular disorders | 1/5 |
| Neurological examination abnormalInvestigations | 1/5 |
| Chest painCardiac disorders | 1/5 |
| BronchitisRespiratory, thoracic and mediastinal disorders | 1/5 |
| Age, Categorical(Participants) | Nitisinone |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 5 |
| >=65 years | 0 |
| Age, Continuous(years) | Nitisinone |
|---|---|
| Mean | 38.8 (24 to 52) |
| Sex: Female, Male(Participants) | Nitisinone |
|---|---|
| Female | 3 |
| Male | 2 |
| Ethnicity (NIH/OMB)(Participants) | Nitisinone |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 4 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Nitisinone |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 4 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
The record gives a start of Apr 2013, a primary completion of Jul 2016 and a completion of Feb 2017. It does not say whether these dates are actual or estimated.
Results were first posted in Nov 2017, 1 year 4 months after primary completion.
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Studies of the drug tested here: Nitisinone
National Eye Institute (NEI) →