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CompletedNCT05969236Updated Jul 9, 2024

A Study of MDI-1228_mesylate Ophthalmic Solution in Healthy Adults

A Phase 1 interventional study of MDI-1228_mesylate Ophthalmic Solution and Placebo in Allergic Conjunctivitis, sponsored by Shanghai Medinno Pharmaceutical Technology Co., Ltd.. Completed at 1 site in Australia. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-07-09.

Sponsored by Shanghai Medinno Pharmaceutical Technology Co., Ltd. · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Apr 2024, 2 years 6 months ago, and no results have been posted to the registry.
Phase
Phase 1
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The main goal of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics (PK) profiles* of MDI-1228_mesylate Ophthalmic Solution in healthy adult participants.

Participants will receive either of the following treatment:

  • MDI-1228_mesylate Ophthalmic Solution, or
  • Placebo**

Researchers will observe any changes in health (if any) in participants receiving the study treatment to evaluate the safety and tolerability*** of the study drug. Researchers will also collect several blood samples from participants to study PK profiles of the drug.

Note:

*PK profiles: how the drug interacts with the body. **placebo: a harmless substance that contains no active agents. ***tolerability: how well you can tolerate the drug.

02

Conditions studied

  • Allergic Conjunctivitis
03

In context

Conjunctivitis, Allergic

210 studies on the registry are indexed under Conjunctivitis, Allergic; 18 are open to participants now.

This study's enrollment of 40 is below the median of 87 across 174 interventional studies indexed under Conjunctivitis, Allergic.

Browse Conjunctivitis, Allergic studies →

Lead sponsor

This is the only study on the registry with Shanghai Medinno Pharmaceutical Technology Co., Ltd. as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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.

Inclusion criteria

  1. Weight ≥ 50 kg for males, ≥ 45 kg for females, with the (BMI = weight[kg]/height[m]2) between 18 and 32 (inclusive) at screening.
  2. The corrected visual acuity (CVA) of both eyes should be 6/6 or 20/20 (Snellen chart), with an intraocular pressure between 10 and 21 mmHg (inclusive) and a difference in intraocular pressure between the 2 eyes \< 5 mmHg at screening.

  3. Normal vital signs after ≥ 5 minutes resting supine or semi supine position:

    1. ≥ 90 mmHg and ≤160 mmHg (systolic blood pressure)
    2. ≥50 mmHg and ≤ 95 mmHg (diastolic blood pressure)
    3. ≥ 45 beats per minute (bpm) and ≤ 100 bpm (heart rate)
    4. Body temperature ≥35.5℃ and ≤37.7℃
    5. Respiratory Rate≥12 breaths/minute and≤22 breaths/minute
  4. Standard 12-lead parameters after ≥5 minutes resting in supine or semi-supine position with PR ≥ 120 ms and ≤ 220 ms, QRSD \< 120 ms, ≤ 450 ms for males and ≤ 470 ms for females, and otherwise normal ECG (all data limits are based on average readings of the ECGs) at screening.
  5. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or use highly effective method as assessed by the PI (OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD) from screening until study completion, including the follow up period for at least 30 days after the last dose of study drug, or be for ≥ 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse as part of their usual lifestyle will also be eligible for participation.
  6. Women of (WOCBP) must have a negative pregnancy test at screening and admission and be willing to have additional pregnancy tests as required throughout the study.
  7. Males must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method as assessed by the PI from screening until study completion, including the follow up period, for at least 30 days after the last dose of study drug. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long- acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse as part of their usual lifestyle and are not planning to conceive will also be eligible.
  8. Male participants must agree to refrain from donating sperm and female participants from donating ova from screening until study completion, including the follow up period, for at least 90 days after the last dose of study drug.
  9. Provides written and is willing and able to undergo all study procedures and attend the scheduled follow up visit/s per protocol.
  10. Are willing to consume clinical research unit (CRU) provided meals.
  11. Have no neck or back issues which prevents the participant having their head tilted back for dosing at the discretion of the Investigator.
  12. Males and females aged 18 to 55 years old (inclusive)
  13. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, safety laboratory tests, and ECG. A potential participant with a clinical abnormality or laboratory parameters outside the normal reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The Investigator may discuss with the local MM and Sponsor MM as required.
  14. Have no abnormal results or abnormal not (as determined by the Investigator) results of ocular examinations of both eyes (including slit-lamp examination, corneal fluorescein staining test, light response pupil test, extraocular movement test, dilated fundus examination)

Exclusion criteria

Exclusion Criteria:

  1. Have a current or past history of circulatory system diseases, respiratory disorders, hepatobiliary disorders, digestive disorders, urinary system diseases, renal disorders, endocrine disorders, immune system disorders, , metabolic disorders, mental disorders, or nervous system diseases that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study. Participant with a history of uncomplicated kidney stones (defined as spontaneous passage and no recurrence in the last 5 years); uncomplicated cholecystectomy; Gilbert's syndrome; a past history of being treated by non-current depression may be enrolled in the study at the discretion of the Investigator. Participants with a history of childhood asthma (without hospitalization) that has symptomatically resolved and remains untreated may participant.
  2. Have healed eye disorders (such as infection, trauma) in either eye within 1 month prior to the first dose.
  3. Have a history of intraocular surgery and laser eye surgery in either eye.
  4. Used any ocular products (including various eye drops or eye gel) within 14 days or 5 half-lives (whichever is longer) prior to screening.
  5. Wore contact lenses within 2 days prior to baseline (Day -1) or need to wear contact lenses throughout the clinical study.
  6. Current evidence or history of COVID-19 or influenza-like illness as defined by fever (> 37.7°C) and 2 or more of the following symptoms within 7 days before dosing: cough, sore throat, runny nose, sneezing, limb/joint pain, headache, vomiting/diarrhea in the absence of a known cause, other than influenza or COVID-19 infection.
  7. A positive pre-study , surface antigen or positive antibody result at screening.
  8. Participants who are intolerant of venipuncture blood collection or have poor venous access and/or have a history of fear of needles and hemophobia.
  9. Used Janus kinase (JAK) inhibitors or or any other prescription drugs, traditional Chinese medicines or Chinese patent medicines within 4 weeks prior to Day -1; or used over-the-counter (OTC) drugs or health products within 2 weeks prior to Day -1, unless with a of more than 5 half-lives for products with a longer half-life. The Principal Investigator may review medication on a case-by-case basis to determine if its use would compromise participant safety or interfere with study procedures or data interpretation.
  10. Was vaccinated within 2 weeks prior to screening or plan to be vaccinated during the study.
  11. Had major surgery within 6 months prior to screening or plan to undergo surgery during the study.
  12. Participants who smoked more than 5 cigarettes/pipes/vaping per day on average or excessive use of any nicotine product (> 5 products on average per day) within 3 months prior to screening and not able to abstain from smoking from screening to end of study (EoS).
  13. Any other serious medical condition or abnormality that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study.
  14. A positive pre-study drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) and may be followed up at the discretion of the Investigator.
  15. History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of > 21 units for males or > 14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits.
  16. The participant is unwilling to abstain from alcohol consumption from 24 hours prior to dosing until discharge from the CRU, and for 24 hours prior to all other outpatient visits to the CRU.
  17. Known history of severe allergic, anaphylactic, or other reactions to chimeric, human or humanized antibodies, fusion proteins, MDI-1228_mesylate Ophthalmic Solution , any material used for assessments (e.g., fluorescein, tropicamide, etc), or a history of drug or other allergy including severe allergic reaction that in the opinion of the Investigator contraindicates their participation.
  18. Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater.
  19. Pregnant or breastfeeding .
  20. Donation within the last 3 months of > 499 mL whole blood or within 2 weeks of any volume of plasma.
  21. Participant unable to provide written or participant under guardianship.
  22. Unwilling or unable to follow protocol requirements, including attendance at follow up visit/s.
  23. Any history of severe ocular trauma in either eye at any time.
  24. Any history of any refractive surgery procedure within the past 6 months of the screening visit in either eye.
  25. Current or chronic history of clinically significant ocular disease within the past 3 months of screening visit in either eye.
  26. Current or chronic history of ocular infection (bacterial, viral, or fungal) or corneal irritation within the past 3 months of screening visit in either eye.
  27. Abnormal tearing, OR expected regular use of prescription or expected use of OTC tear substitutes within 4 weeks prior to Day -1, and for the duration of the study.
  28. Previous or expected use of ocular (topical, periocular, intravitreal), local (inhaled or nasal), or systemic or glucocorticoid medications within 4 weeks prior to Day -1, and for the duration of the study.
  29. At the Investigator's or delegate's discretion, any participants who have a history of any significant ocular conditions in either eye that would contraindicate the use of the study medication, or that might affect the study conduct, or the interpretation of the study results.
  30. Clinically significant findings as determined by the Investigator in other ocular examinations (e.g., conjunctival hyperemia grade >1, corneal fluorescein staining score ≥ 2, or other chronic or acute eye disorders).
  31. History of clinically significant ocular disease (glaucoma, retinal detachment, iritis, uveitis, herpetic keratitis, etc.) that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the participant by virtue of their participation in the study.
  32. Presence of an ocular pathology such as blepharitis, conjunctivitis, uveitis, or any other ocular infection or inflammation.
Terms in these criteria, in plain language(17)

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.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

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.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

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.

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.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

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.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Washout period

A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Double (Participant, Investigator)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Experimental Group

    Including 2 single dose groups (Part A) and 2 multiple dose groups (Part B). Participants in experimental groups will receive MDI-1228_mesylate Ophthalmic Solution.

    Drug: MDI-1228_mesylate Ophthalmic Solution

  • Placebo comparator
    Comparator Group

    One comparator group will be set for each of the 4 experimental groups, to a total of 4 comparator groups. Participants in comparator groups will receive placebo.

    Drug: Placebo

Interventions

  • DrugMDI-1228_mesylate Ophthalmic Solution

    MDI-1228_mesylate Ophthalmic Solution includes 2 strengths: * 0.1% (0.4 mL \[0.4 mg\] free base) * 0.3% (0.4 mL \[1.2 mg\] free base)

  • DrugPlacebo

    The components employed in the placebo formulation are the same as those used for the active formulation except MDI-1228_mesylate is absent.

06

What researchers measure

Primary outcomes

  1. Part A and B - Incidence and severity of all systemic or ocular treatment emergent adverse events (TEAEs)

    Systemic or ocular TEAEs will be collected from spontaneous reports and direct observation. The investigator will make an assessment of intensity for each TEAE and assign it to one of the Common Terminology Criteria for Adverse Events (CTCAE) categories: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death).

    Time frame: From first dose to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  2. Part A and B - Assessment of vital sign measurement results - respiratory rate

    Respiratory rate (breaths/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  3. Part A and B - Assessment of vital sign measurement results - heart rate

    Heart rate (beats/minute) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  4. Part A and B - Assessment of vital sign measurement results - blood pressure

    Blood pressure (mmHg) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  5. Part A and B - Assessment of vital sign measurement results - body temperature

    Body temperature (℃) will be measured while the participant is at rest in a supine or semi-supine position (after ≥ 5 minutes resting supine or semi-supine), to monitor and record any abnormal clinically significant changes from baseline and incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  6. Part A and B - Assessment of physical examination results - general appearance

    Assessment of general appearance (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  7. Part A and B - Assessment of physical examination results - head, eyes, ears, nose, and throat (HEENT)

    Assessment of HEENT (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  8. Part A and B - Assessment of physical examination results - neck (including thyroid and nodes)

    Assessment of neck (including thyroid and nodes) (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  9. Part A and B - Assessment of physical examination results - cardiovascular system

    Assessment of cardiovascular system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  10. Part A and B - Assessment of physical examination results - respiratory system

    Assessment of respiratory system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  11. Part A and B - Assessment of physical examination results - gastrointestinal system

    Assessment of gastrointestinal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  12. Part A and B - Assessment of physical examination results - renal system

    Assessment of renal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  13. Part A and B - Assessment of physical examination results - neurological system

    Assessment of neurological system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  14. Part A and B - Assessment of physical examination results - musculoskeletal system

    Assessment of musculoskeletal system (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  15. Part A and B - Assessment of physical examination results - skin

    Assessment of skin (normal/abnormal) will be performed at screening, and may be performed at various scheduled/unscheduled time points if deemed necessary by the Investigator, to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  16. Part A and B - Assessment of 12-lead electrocardiogram (ECG) results - heart rate

    12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in heart rate (beats/min) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate (repeat for 3 times), with 1- to 2-minute intervals between ECG readings.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  17. Part A and B - Assessment of 12-lead ECG results - PR interval

    12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in PR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  18. Part A and B - Assessment of 12-lead ECG results - QRSD interval

    12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QRSD interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  19. Part A and B - Assessment of 12-lead ECG results - QT interval corrected with Fridericia Formula (QTcF)

    12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in QTcF (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  20. Part A and B - Assessment of 12-lead ECG results - RR interval

    12-lead ECG measurements will be performed to monitor and record any abnormal clinically significant changes in RR interval (milliseconds) as well as the result interpretation from baseline and incidence of such changes after treatment until the last visit. All ECG measurements will be recorded in triplicate, with 1- to 2-minute intervals between ECG readings.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  21. Part A and B - Ophthalmic assessment - corrected visual acuity (CVA)

    CVA (measured using Snellen chart) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  22. Part A and B - Ophthalmic assessment - intraocular pressure

    Intraocular pressure (mmHg) will be assessed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  23. Part A and B - Ophthalmic assessment - light response pupil test

    Light response pupil test (positive/negative) will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  24. Part A and B - Ophthalmic assessment - extraocular movement test

    Extraocular movement test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  25. Part A and B - Ophthalmic assessment - slit-lamp examination

    Slit-lamp examination will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  26. Part A and B - Ophthalmic assessment - corneal fluorescein staining test

    Corneal fluorescein staining test will be performed to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of study (EOS, Day 7±1 day in Part A, Day 14±1 day in Part B)

  27. Part A and B - Ophthalmic assessment - dilated fundus examination

    Dilated fundus examination will be performed at screening, Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline and the incidence of such changes after treatment until the last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  28. Part A and B - Assessment of hematology results - red blood cell distribution width

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in red blood cell distribution width (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  29. Part A and B - Assessment of hematology results - hemoglobin

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hemoglobin (g/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  30. Part A and B - Assessment of hematology results - hematocrit

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in hematocrit (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  31. Part A and B - Assessment of hematology results - red blood cell count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in red blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  32. Part A and B - Assessment of hematology results - white blood cell count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in white blood cell count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  33. Part A and B - Assessment of hematology results - absolute neutrophil count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in absolute neutrophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  34. Part A and B - Assessment of hematology results - neutrophil percentage

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in neutrophil percentage (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  35. Part A and B - Assessment of hematology results - absolute lymphocyte count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in absolute lymphocyte count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  36. Part A and B - Assessment of hematology results - lymphocyte percentage

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lymphocyte percentage (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  37. Part A and B - Assessment of hematology results - absolute monocyte count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in absolute monocyte count (cells/μL)) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  38. Part A and B - Assessment of hematology results - monocyte percentage

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in monocyte percentage (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  39. Part A and B - Assessment of hematology results - absolute basophil count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in absolute basophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  40. Part A and B - Assessment of hematology results - basophil percentage

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in basophil percentage (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  41. Part A and B - Assessment of hematology results - absolute eosinophil count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in absolute eosinophil count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  42. Part A and B - Assessment of hematology results - eosinophil percentage

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in eosinophil percentage (%) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  43. Part A and B - Assessment of hematology results - platelet count

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in platelet count (cells/μL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  44. Part A and B - Assessment of hematology results - mean cell hemoglobin

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in mean cell hemoglobin (pg/cell) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  45. Part A and B - Assessment of hematology results - mean cell volume

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in mean cell volume (fL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  46. Part A and B - Assessment of hematology results - mean cell hemoglobin concentration

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in mean cell hemoglobin concentration (g/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  47. Part A and B - Assessment of hematology results - mean platelet volume

    Hematology tests will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in mean platelet volume (fL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  48. Part A and B - Assessment of coagulation results - international normalized ratio (INR)

    A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in INR from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  49. Part A and B - Assessment of coagulation results - activated partial thromboplastin time (aPTT)

    A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in aPTT (seconds) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  50. Part A and B - Assessment of coagulation results - prothrombin time (PT)

    A coagulation test will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in PT (seconds) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  51. Part A and B - Assessment of blood biochemistry results - sodium

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood sodium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  52. Part A and B - Assessment of blood biochemistry results - potassium

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood potassium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  53. Part A and B - Assessment of blood biochemistry results - chloride

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood chloride (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  54. Part A and B - Assessment of blood biochemistry results - calcium

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  55. Part A and B - Assessment of blood biochemistry results - bicarbonate

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood bicarbonate (mmol/L) and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  56. Part A and B - Assessment of blood biochemistry results - albumin

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in blood albumin (g/dL) and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  57. Part A and B - Assessment of blood biochemistry results - total protein

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total protein (g/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  58. Part A and B - Assessment of blood biochemistry results - creatinine

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood creatinine (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  59. Part A and B - Assessment of blood biochemistry results - creatine kinase

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood creatine kinase (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  60. Part A and B - Assessment of blood biochemistry results - estimated glomerular filtration rate (GFR)

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes from baseline in estimated GFR (mL/min) and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  61. Part A and B - Assessment of blood biochemistry results - urea

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood urea (μmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  62. Part A and B - Assessment of blood biochemistry results - aspartate aminotransferase (AST)

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in AST (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  63. Part A and B - Assessment of blood biochemistry results - alanine aminotransferase (ALT)

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALT (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  64. Part A and B - Assessment of blood biochemistry results - gamma glutamyl transpeptidase (GGT)

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in GGT (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  65. Part A and B - Assessment of blood biochemistry results - alkaline phosphatase (ALP)

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in ALP (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  66. Part A and B - Assessment of blood biochemistry results - phosphate

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood phosphate (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  67. Part A and B - Assessment of blood biochemistry results - total bilirubin

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in total bilirubin (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  68. Part A and B - Assessment of blood biochemistry results - direct bilirubin

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in direct bilirubin (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  69. Part A and B - Assessment of blood biochemistry results - indirect bilirubin

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in indirect bilirubin (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  70. Part A and B - Assessment of blood biochemistry results - amylase

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood amylase (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  71. Part A and B - Assessment of blood biochemistry results - cholesterol

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in cholesterol (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  72. Part A and B - Assessment of blood biochemistry results - high density lipoprotein (HDL)/cholesterol ratio

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in HDL/cholesterol ratio from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  73. Part A and B - Assessment of blood biochemistry results - high density lipoprotein (HDL) cholesterol

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in HDL cholesterol (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  74. Part A and B - Assessment of blood biochemistry results - low density lipoprotein (LDL) cholesterol/high density lipoprotein (HDL) cholesterol ratio

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in LDL/HDL cholesterol ratio from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  75. Part A and B - Assessment of blood biochemistry results - low density lipoprotein (LDL) cholesterol

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in LDL cholesterol (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  76. Part A and B - Assessment of blood biochemistry results - non-high density lipoprotein (HDL) cholesterol

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in non-HDL cholesterol (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  77. Part A and B - Assessment of blood biochemistry results - triglycerides

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in triglycerides (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  78. Part A and B - Assessment of blood biochemistry results - uric acid

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in uric acid (μmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  79. Part A and B - Assessment of blood biochemistry results - lactate dehydrogenase

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in lactate dehydrogenase (units/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  80. Part A and B - Assessment of blood biochemistry results - magnesium

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood magnesium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  81. Part A and B - Assessment of blood biochemistry results - glucose

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in blood glucose (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  82. Part A and B - Assessment of blood biochemistry results - anion gap

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in anion gap (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  83. Part A and B - Assessment of blood biochemistry results - adjusted calcium

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in adjusted calcium (mmol/L) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  84. Part A and B - Assessment of blood biochemistry results - globulin

    Blood biochemistry will be measured at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in globulin (g/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  85. Part A and B - Assessment of urinalysis results - pH

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in pH from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  86. Part A and B - Assessment of urinalysis results - specific gravity

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in specific gravity from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  87. Part A and B - Assessment of urinalysis results - urine glucose

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine glucose (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  88. Part A and B - Assessment of urinalysis results - urine protein

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine protein (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  89. Part A and B - Assessment of urinalysis results - urine bilirubin

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine bilirubin (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  90. Part A and B - Assessment of urinalysis results - urine ketones

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine ketones (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  91. Part A and B - Assessment of urinalysis results - urine blood

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine blood (negative/+/++/+++) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  92. Part A and B - Assessment of urinalysis results - urine nitrite

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine nitrite (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  93. Part A and B - Assessment of urinalysis results - urine urobilinogen

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in urine urobilinogen (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  94. Part A and B - Assessment of urinalysis results - leucocyte esterase

    Urinalysis will be performed at screening, baseline (not required if screening assessment done within 3 days), Day 2 visit (Part A) or Day 8 visit (Part B) to monitor and record any abnormal clinically significant changes in leucocyte esterase (mg/dL) from baseline and the incidence of such changes after treatment until last visit.

    Time frame: From screening to end of treatment (Day 2 in Part A, Day 8 in Part B)

  95. Part A and B - Assessment of scores of conjunctival hyperemia

    Scores of conjunctival hyperemia (0 to 4 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.

    Time frame: From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)

  96. Part A and B - Assessment of scores of corneal staining

    Scores of corneal staining (0 to 5 scores, a higher score indicates a more severe condition) will be assessed to record the change from the pre-dose (Day -1) scores to the post-dose scores (Day 2 for Part A, Day 8 for Part B) in the study eye.

    Time frame: From pre-dose to post-dose (Day 2 in Part A, Day 8 in Part B)

Secondary outcomes

  1. Part A - Maximum concentration (Cmax) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution

    Cmax means the highest concentration a drug reaches in the plasma after administration. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day)

  2. Part A and B - Time to maximum concentration (Tmax) of MDI-1228_mesylate Ophthalmic Solution

    Tmax refers to the time a drug takes to reach the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)

  3. Part A and B - Half-life (T1/2) of MDI-1228_mesylate Ophthalmic Solution

    T1/2 refers to the time a drug takes to be eliminated to half of the highest concentration in the plasma after administration. It will be measured after the subject receives a single dose (Part A) or multiple doses (Part B) of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day in Part A, Day 14±1 day in Part B)

  4. Part A - Systemic clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution

    Systemic CL refers to the total volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day)

  5. Part A - Volume of distribution (Vd) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution

    Vd refers to fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day)

  6. Part A - Mean retention time (MRT) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution

    MRT reflects the average time a drug molecule spends in the body. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day)

  7. Part A - Area under curve until time t (AUC0-t) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution

    AUC0-t refers to area under the plasma concentration-time curve until time t and reflects the actual body exposure to drug after administration at time t. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day)

  8. Part A - Area under curve until infinity (AUC0-∞) of MDI-1228_mesylate Ophthalmic Solution after a single dose of MDI-1228_mesylate Ophthalmic Solution

    AUC0-∞ refers to area under the plasma concentration-time curve until infinity and reflects the total body exposure to drug. It will be measured after the subject receives a single dose of MDI-1228_mesylate Ophthalmic Solution by instillation into the study eye (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 7±1 day)

  9. Part B - Trough concentration at steady state (Css_min) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution

    Css_min means the lowest concentration of drug in the blood within a steady-state dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 14±1 day)

  10. Part B - Maximum plasma concentration at steady state (Css_max) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution

    Css_max means the highest concentration of drug in the blood observed after intermittent dosage administration. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 14±1 day)

  11. Part B - Average plasma concentration at steady state (Css_av) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution

    Css_av means the average drug concentration reached during a steady-state intermittent dosing interval. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 14±1 day)

  12. Part B - Clearance (CL or CL/F) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution

    CL means the volume of fluid cleared of drug from the body per unit of time, usually expressed in mL/min. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 14±1 day)

  13. Part B - Area under the plasma concentration-time curve at steady state (AUCss) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution

    AUCss reflects the exposure of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 14±1 day)

  14. Part B - Coefficient of fluctuation (DF) of MDI-1228_mesylate Ophthalmic Solution following multiple doses of MDI-1228_mesylate Ophthalmic Solution

    DF reflects difference between the highest and lowest concentration of drug in the body at steady state. It will be measured after administration of multiple doses of MDI-1228_mesylate Ophthalmic Solution by conjunctival instillation (2 drops).

    Time frame: Post-first dose on Day 1 to EOS (Day 14±1 day)

07

Study locations

1 site
  • CMAX Clinical Research
    Adelaide, South Australia 5000, Australia
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2023 to primary completion in Apr 2024, 6 months.

How these figures are worked out, and which studies are left out of them.

Registered
Jul 24, 2023
First posted
Aug 1, 2023
StartActual
Oct 6, 2023
Primary completionActual
Apr 30, 2024
CompletionActual
May 30, 2024
Last update
Jul 9, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05969236
Lead sponsor
Shanghai Medinno Pharmaceutical Technology Co., Ltd.
Responsible party
Sponsor
First posted
Aug 1, 2023
Start date
Oct 6, 2023
Primary completion
Apr 30, 2024
Completion
May 30, 2024
Last update
Jul 9, 2024

Study contacts

Sepehr Shakib, PhD
principal investigator · CMAX Clinical Research
Liang Lu, PhD
study director · Shanghai Medinno Pharmaceutical Technology Co., Ltd.

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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