A Phase 3 interventional study of A4250 (odevixibat) in Progressive Familial Intrahepatic Cholestasis, sponsored by Albireo, an Ipsen Company. Completed at 41 sites in 15 countries. Open to participants aged 0 Months to 100 Years. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Albireo, an Ipsen Company (part of Ipsen) · Phase 3, Interventional, and Treatment
Open-label extension study to evaluate long-term safety and persistence of effect of A4250 in children with progressive familial intrahepatic cholestasis (PFIC).
33 studies on the registry are indexed under Cholestasis, progressive familial intrahepatic 1; 13 are open to participants now.
This study's enrollment of 116 is above the median of 60 across 11 interventional studies indexed under Cholestasis, progressive familial intrahepatic 1.
Browse Cholestasis, progressive familial intrahepatic 1 studies →Albireo, an Ipsen Company is the lead sponsor of 5 studies on the registry; none are open to participants now.
First submitted before Albireo became part of Ipsen.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria Cohort 1:
Inclusion Criteria Cohort 2:
Exclusion Criteria Cohort 1:
Exclusion Criteria Cohort 2:
Patient with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following:
Patient suffers from uncontrolled, recalcitrant pruritic condition other than PFIC.
Examples include, but not limited to, atopic dermatitis or other primary pruritic skin diseases.
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.
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.
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.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on 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.
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.
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.
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.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on 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.
Capsules for oral administration (40 or 120 µg/kg) once daily for 72 weeks, or 40 µg/kg/day for the first 12 weeks followed by 120 µg/kg/day for the remaining 60 weeks. Patients participating in the optional extension period will continue at the same dose as at the end of the 72-week treatment period.
Drug: A4250 (odevixibat)
A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).
Percentage of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument (Combined AM and PM Scores)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments recorded by each participant multiplied by 100. The data reported represent the combination of pruritus assessments from both AM and PM scores.
Time frame: Week 72
Change From Baseline in Serum Bile Acids at Week 72
Blood samples for analysis of fasting total serum bile acids were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for serum bile acids. Exceptions were made for infants \<12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the A4250-008 study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (NCT03566238).
Time frame: Baseline and Week 72
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, and 0-70 (Combined AM and PM Scores)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. The data reported represent the combination of pruritus assessments from both AM and PM scores.
Time frame: Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, and Weeks 0-70
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, 0-70, and 0-72 (AM Score)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. AM score represents night-time itching/scratching and sleep disturbance.
Time frame: Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, Weeks 0-70, and Weeks 0-72
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 0-4, 0-12, 0-22, 0-24, 0-36, 0-46, 0-48, 0-60, 0-70, and 0-72 (PM Score)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. PM score represents daytime itching/scratching and tiredness.
Time frame: Weeks 0-4, Weeks 0-12, Weeks 0-22, Weeks 0-24, Weeks 0-36, Weeks 0-46, Weeks 0-48, Weeks 0-60, Weeks 0-70, and Weeks 0-72
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72 and Every 16 Weeks During the Optional Extension Period
Blood samples for analysis of fasting total serum bile acids were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for serum bile acids. Exceptions were made for infants \<12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat, and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the A4250-008 study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (NCT03566238).
Time frame: Baseline and Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument From Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76 (Combined AM and PM Scores)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. The data reported represent the combination of pruritus assessments from both AM and PM scores.
Time frame: Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. AM score represents night-time itching/scratching and sleep disturbance.
Time frame: Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76
Percentage of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score)
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. PM score represents daytime itching/scratching and tiredness.
Time frame: Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 44-46, 47-48, 58-60, 68-70, 71-72, and 73-76
Percentage of Responders for Pruritus Assessments Bi-Weekly (Combined AM and PM Scores)
A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change of 1.0 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction against the threshold value of 1.0 based on bi-weekly scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. The data reported represent the combination of pruritus assessments from both AM and PM scores.
Time frame: Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18, 19-20, 21-22, 23-24, 35-36, 47-48, 59-60, and 71-72
Percentage of Responders for Pruritus Assessments Monthly (Combined AM and PM Scores)
A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change of 1.0 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction against the thresholds value of 1.0 based on monthly scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. The data reported represent the combination of pruritus assessments from both AM and PM scores.
Time frame: Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 45-48, 58-60, and 68-72
Percentage of Participants Achieving a Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO (Combined AM and PM Scores)
The percentage of participants who achieved positive pruritus assessment for more than 50% of the time for Weeks 0-72 is reported. A positive pruritus assessment is defined as a scratching score of \<=1 or at least a 1-point decrease from baseline on the Albireo ObsRO instrument based on rounded baseline and was calculated based on reported eDiary data. At each assessment, the AM score was compared to the baseline AM average, and the PM score was compared to the baseline PM average. The data reported represent the combination of pruritus assessments from both AM and PM scores.
Time frame: Week 72
Number of Participants Who Underwent Biliary Diversion Surgery and/or Liver Transplantation
Participants who underwent BDS and/or liver transplantation are reported.
Time frame: Weeks 24, 48, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, 328, 344, and 360
Change From Baseline in Height Z-Scores During Treatment Period and the Optional Extension Period
Height was measured using certified stadiometer. Change in growth parameters was assessed using linear growth (height) compared to standard growth curve (Z-score) calculated by using the software or methods from the Centers for Disease Control (CDC) website for participants with age \>=2 years old and from the World Health Organization (WHO) website for participants with age \<2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to first dose of study treatment in the A4250-008 study. A Z-score indicates how many standard deviation's (SD) a participant's height measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below average a measurement was.
Time frame: Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Change From Baseline in Weight Z-Scores During Treatment Period and the Optional Extension Period
Weight was measured using certified weight scale. Change in growth parameters was assessed using linear growth (weight) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age \>=2 years old and from the WHO website for participants with age \<2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. The Z-score indicates how many SDs a participant's weight measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was.
Time frame: Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Change From Baseline in Body Mass Index (BMI) Z-Scores During Treatment Period and the Optional Extension Period
BMI was calculated by weight (kg) / height (m)\^2 which were measured by the standardized assessments. Change in growth parameters was assessed using linear growth (BMI) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age \>=2 years old and from the WHO website for participants with age \<2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. The Z-score indicates how many SDs a participant's BMI measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was.
Time frame: Baseline and Weeks 12, 24, 36, 48, 60, 70, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, 312, and 328
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72
The number of participants with use of UDCA and/or rifampicin are reported.
Time frame: Weeks 24, 48, and 72
Change From Baseline to Week 72 During Treatment Period and During the Optional Extension Period in Pediatric End-Stage Liver Disease (PELD) Score
The PELD score was calculated for children under 12 years of age, ranged across negative to positive values. Calculation of PELD score was done by converting the laboratory parameters: total bilirubin in milligram/deciliter (mg/dL), albumin in gram (g)/dL, and creatinine in mg/dL laboratory parameters were converted to units. PELD score was calculated as 4.80\*ln (total bilirubin)+18.57\*ln \[international normalized ratio (INR)\] - 6.87\*ln (albumin) + 4.36 (if participant \<1 year: scores for participants listed for liver transplantation before the participant's first birthday continued to include the value assigned for age (\<1 year) until the participant reached the age of 24 months)+6.67 (if the participant has growth failure \[\<-2 SD\]). The laboratory values \<1.0 were set to 1.0 for the calculation of PELD score. Lower scores represent less severe hepatic disease. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
Time frame: Baseline and Weeks 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 232, 248, 264, 280, 296, and 312
Change From Baseline to Week 72 During Treatment Period and During the Optional Extension Period in Model for End-stage Liver Disease (MELD) Score for Children 12 Years of Age or Older
MELD score was calculated for children 12 years of age or older ranges from 6 to 40. Calculation of MELD score was done by converting the laboratory parameters in the following units: total bilirubin in mg/dL, albumin in g/dL, and creatinine in mg/dL laboratory parameters were converted to units. MELD score was calculated as 9.57\*ln (creatinine)+3.78\*ln (total bilirubin)+11.2 \*ln (INR)+6.43. Laboratory values \<1.0 were set to 1.0 and serum creatinine values \>4.0 mg/dL were set to 4.0 for calculation of the MELD score. Lower scores represent less severe hepatic disease. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. All assessments after intercurrent events (premature treatment discontinuation, death, or initiation of rescue treatments such as biliary diversion surgery or liver transplantation) or follow-up assessments (\>= last dose day+15 days) were excluded from analysis.
Time frame: Baseline and Weeks 72, 88, 104, and 120
Change From Baseline to Week 72 in Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) Score
The AST to APRI score was calculated as \[(AST in units per liter {U/L})/ (AST upper limit of normal {ULN} in U/L)\] \* 100/ (platelets in 10\^9/L). The APRI score is a way to assess fibrosis of the liver. The lower the APRI score (\< 0.5), the greater the negative predictive value and ability to rule out cirrhosis; the higher the value (\> 1.5) the greater the positive predictive value and ability to rule in cirrhosis. Lower values indicate less severe hepatic fibrosis. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
Time frame: Baseline and Week 72
Change From Baseline to Week 72 in Fibrosis-4 (Fib-4) Score
Fib-4 score was calculated as (age \* AST in U/L)/ (platelets in 10\^9/L \*√ ( alanine aminotransferase \[ALT\] in U/L). The FIB-4 score estimates the amount of scarring in the liver. A FIB-4 score \<1.45 has a negative predictive value of 90% for advanced fibrosis (Ishak fibrosis score 4-6 which includes early bridging fibrosis to cirrhosis). In contrast, a FIB-4 score \> 3.25 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis. Lower values indicate less severe hepatic fibrosis. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
Time frame: Baseline and Week 72
This Phase III, open-label extension study was conducted in participants with progressive familial intrahepatic cholestasis (PFIC) at 43 centers in 13 countries.
| Milestone | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Started | 19 | 37 | 60 |
| Completed | 15 | 28 | 40 |
| Not completed | 4 | 9 | 20 |
| Withdrew: Adverse event | 2 | 1 | 6 |
| Withdrew: Withdrawal of consent/assent | 1 | 4 | 4 |
| Withdrew: Physician decision | 0 | 1 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 |
| Withdrew: Other | 1 | 3 | 9 |
| Milestone | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Started | 14 | 27 | 33 |
| Completed | 0 | 0 | 0 |
| Not completed | 14 | 27 | 33 |
| Withdrew: Adverse event | 0 | 0 | 1 |
| Withdrew: Withdrawal of consent/assent | 0 | 1 | 2 |
| Withdrew: Physician decision | 0 | 0 | 1 |
| Withdrew: Transition to commercial drug | 8 | 21 | 16 |
| Withdrew: Other | 6 | 5 | 13 |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments recorded by each participant multiplied by 100. The data reported represent the combination of pruritus assessments from both AM and PM scores.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Percentage of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument (Combined AM and PM Scores) | 55.20 ± 38.733 | 38.58 ± 34.877 | 77.28 ± 28.084 |
Blood samples for analysis of fasting total serum bile acids were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for serum bile acids. Exceptions were made for infants \<12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the A4250-008 study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (NCT03566238).
| micromole per liter (µmol/L) | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Change From Baseline in Serum Bile Acids at Week 72 | -104.00 ± 167.318 | -139.84 ± 172.070 | -57.97 ± 137.990 |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. The data reported represent the combination of pruritus assessments from both AM and PM scores.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 0 - 4 | 45.72 ± 34.300 | 23.64 ± 27.005 | 60.14 ± 33.985 |
| Weeks 0 - 12 | 51.05 ± 37.670 | 27.34 ± 28.687 | 67.63 ± 33.645 |
| Weeks 0 - 22 | 56.01 ± 38.537 | 31.09 ± 31.859 | 70.05 ± 33.858 |
| Weeks 0 - 24 | 56.00 ± 38.331 | 31.45 ± 32.324 | 68.55 ± 34.116 |
| Weeks 0 - 36 | 54.63 ± 38.243 | 33.66 ± 33.704 | 69.97 ± 33.872 |
| Weeks 0 - 46 | 60.41 ± 39.491 | 34.70 ± 35.593 | 75.46 ± 29.801 |
| Weeks 0 - 48 | 61.61 ± 39.936 | 33.56 ± 35.668 | 74.79 ± 30.843 |
| Weeks 0 - 60 | 57.80 ± 38.873 | 33.18 ± 34.935 | 74.89 ± 30.434 |
| Weeks 0 - 70 | 58.18 ± 38.766 | 40.59 ± 34.928 | 75.60 ± 29.514 |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. AM score represents night-time itching/scratching and sleep disturbance.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 0-4 | 42.38 ± 36.177 | 23.72 ± 29.373 | 58.19 ± 36.799 |
| Weeks 0-12 | 46.88 ± 39.701 | 26.63 ± 30.572 | 65.16 ± 36.029 |
| Weeks 0-22 | 53.74 ± 38.913 | 29.93 ± 33.265 | 67.31 ± 36.277 |
| Weeks 0-24 | 53.87 ± 38.616 | 30.30 ± 33.659 | 66.22 ± 36.445 |
| Weeks 0-36 | 52.88 ± 38.961 | 33.52 ± 34.669 | 66.71 ± 36.704 |
| Weeks 0-46 | 59.94 ± 40.507 | 36.57 ± 35.154 | 72.08 ± 34.694 |
| Weeks 0-48 | 59.35 ± 40.430 | 35.31 ± 35.281 | 71.72 ± 34.880 |
| Weeks 0-60 | 55.95 ± 40.297 | 34.46 ± 34.898 | 70.67 ± 35.983 |
| Weeks 0-70 | 56.44 ± 40.305 | 44.04 ± 34.957 | 73.22 ± 33.511 |
| Weeks 0-72 | 53.68 ± 40.506 | 40.42 ± 34.646 | 73.37 ± 33.127 |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments by each participant multiplied by 100. PM score represents daytime itching/scratching and tiredness.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 0-4 | 49.01 ± 35.687 | 24.13 ± 30.344 | 62.08 ± 34.404 |
| Weeks 0-12 | 55.46 ± 37.829 | 28.74 ± 31.854 | 69.10 ± 34.166 |
| Weeks 0-22 | 58.24 ± 38.888 | 32.29 ± 34.986 | 72.10 ± 33.755 |
| Weeks 0-24 | 58.09 ± 38.893 | 32.62 ± 35.323 | 71.46 ± 33.961 |
| Weeks 0-36 | 56.34 ± 38.352 | 33.50 ± 35.869 | 72.49 ± 33.598 |
| Weeks 0-46 | 60.90 ± 39.159 | 34.13 ± 37.069 | 78.98 ± 28.043 |
| Weeks 0-48 | 63.84 ± 40.035 | 33.02 ± 37.010 | 77.91 ± 29.271 |
| Weeks 0-60 | 59.63 ± 38.401 | 32.99 ± 36.104 | 76.77 ± 28.845 |
| Weeks 0-70 | 59.92 ± 38.190 | 41.02 ± 35.281 | 79.72 ± 26.514 |
| Weeks 0-72 | 56.73 ± 38.087 | 38.24 ± 36.061 | 81.38 ± 25.692 |
Blood samples for analysis of fasting total serum bile acids were drawn at specified timepoints. Participants were to fast (water intake only) for at least 4 hours prior to the collection of samples for serum bile acids. Exceptions were made for infants \<12 months of age if unable to fast for the full 4 hours. Baseline for Cohort 1 placebo/odevixibat, and Cohort 2 groups was defined as the average of last 2 values before the first dose of study treatment in the A4250-008 study. Baseline for Cohort 1 odevixibat/odevixibat group was defined as average of last 2 values before the first dose of study treatment in study A4250-005 (NCT03566238).
| µmol/L | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Week 4 | -115.76 ± 151.014 | -118.78 ± 172.353 | -76.92 ± 94.662 |
| Week 12 | -98.39 ± 149.118 | -109.90 ± 176.472 | -65.01 ± 136.303 |
| Week 22 | -138.67 ± 147.069 | -125.18 ± 165.395 | -73.24 ± 126.319 |
| Week 24 | -112.96 ± 175.107 | -133.52 ± 191.550 | -65.37 ± 128.580 |
| Weeks 36 | -129.41 ± 179.357 | -114.19 ± 200.789 | -60.90 ± 128.520 |
| Week 46 | -166.05 ± 195.963 | -156.88 ± 157.687 | -63.80 ± 128.199 |
| Week 48 | -145.65 ± 177.520 | -121.73 ± 114.214 | -57.90 ± 143.238 |
| Week 60 | -86.46 ± 159.360 | -133.17 ± 162.933 | -43.31 ± 125.923 |
| Week 70 | -149.02 ± 186.918 | -146.43 ± 196.501 | -50.08 ± 140.232 |
| Week 72 | -101.31 ± 169.631 | -123.44 ± 143.220 | -52.39 ± 156.473 |
| Week 88 | -78.11 ± 142.571 | -184.56 ± 182.667 | -65.26 ± 146.498 |
| Week 104 | -115.00 ± 158.790 | -177.90 ± 183.938 | -74.13 ± 154.391 |
| Week 120 | -129.50 ± 141.707 | -178.15 ± 200.653 | -62.89 ± 142.024 |
| Week 136 | -136.82 ± 161.705 | -189.25 ± 218.495 | -89.15 ± 141.661 |
| Week 152 | -137.38 ± 169.254 | -219.53 ± 203.105 | -84.32 ± 150.532 |
| Week 168 | -126.10 ± 165.023 | -233.69 ± 206.932 | -75.91 ± 137.340 |
| Week 184 | -54.50 ± 173.829 | -232.31 ± 198.534 | -32.50 ± 174.063 |
| Week 200 | -60.33 ± 151.529 | -215.45 ± 175.341 | -55.57 ± 191.520 |
| Week 216 | -105.67 ± 148.565 | -254.78 ± 153.536 | -51.00 ± 50.061 |
| Week 232 | -106.00 ± 144.442 | -270.63 ± 158.425 | -42.50 ± 66.359 |
| Week 248 | 23.50 ± 52.678 | -282.88 ± 161.591 | -64.67 ± 56.507 |
| Week 264 | 38.00 ± NA | -258.43 ± 173.286 | -66.67 ± 57.110 |
| Week 280 | 136.00 ± 113.137 | -199.92 ± 97.446 | -1.00 ± 127.986 |
| Week 296 | — | -223.30 ± 81.791 | -90.50 ± NA |
| Week 312 | — | -216.70 ± 91.674 | -90.50 ± NA |
| Week 328 | — | -360.50 ± NA | — |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. The data reported represent the combination of pruritus assessments from both AM and PM scores.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 1-4 | 45.72 ± 34.300 | 23.64 ± 27.005 | 60.14 ± 33.985 |
| Weeks 5-8 | 53.75 ± 39.894 | 28.76 ± 32.349 | 71.14 ± 34.866 |
| Weeks 9-12 | 54.01 ± 41.345 | 29.64 ± 35.594 | 71.03 ± 36.961 |
| Weeks 13-16 | 57.47 ± 42.420 | 31.78 ± 36.364 | 72.19 ± 39.221 |
| Weeks 17-20 | 55.28 ± 41.441 | 36.15 ± 38.564 | 73.95 ± 38.051 |
| Weeks 21-24 | 55.62 ± 42.927 | 35.83 ± 40.132 | 73.11 ± 37.875 |
| Weeks 34-36 | 58.24 ± 41.117 | 32.79 ± 39.066 | 72.39 ± 35.581 |
| Weeks 44-46 | 67.33 ± 39.242 | 38.40 ± 43.144 | 77.11 ± 31.712 |
| Weeks 47-48 | 67.31 ± 43.702 | 34.71 ± 42.594 | 71.86 ± 39.020 |
| Weeks 58-60 | 65.82 ± 40.745 | 44.22 ± 43.534 | 72.31 ± 38.008 |
| Weeks 68-70 | 62.43 ± 40.321 | 56.79 ± 42.935 | 69.40 ± 39.034 |
| Weeks 71-72 | 57.65 ± 39.797 | 55.75 ± 45.076 | 72.26 ± 38.680 |
| Weeks 73-76 | 41.59 ± 39.923 | 63.48 ± 29.003 | 74.47 ± 33.736 |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. AM score represents night-time itching/scratching and sleep disturbance.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 1-4 | 42.38 ± 36.177 | 23.72 ± 29.373 | 58.19 ± 36.799 |
| Weeks 5-8 | 48.16 ± 42.655 | 27.70 ± 34.144 | 69.00 ± 38.199 |
| Weeks 9-12 | 50.57 ± 42.880 | 28.41 ± 37.802 | 68.96 ± 38.876 |
| Weeks 13-16 | 53.47 ± 43.689 | 31.70 ± 38.438 | 69.03 ± 41.902 |
| Weeks 17-20 | 53.94 ± 42.837 | 35.37 ± 40.673 | 71.30 ± 40.934 |
| Weeks 21-24 | 55.52 ± 44.798 | 35.15 ± 41.940 | 69.63 ± 40.353 |
| Weeks 34-36 | 57.49 ± 43.512 | 34.80 ± 39.644 | 69.92 ± 37.610 |
| Weeks 44-46 | 67.07 ± 42.321 | 40.11 ± 43.580 | 73.62 ± 37.122 |
| Weeks 47-48 | 63.67 ± 46.870 | 35.60 ± 42.748 | 69.18 ± 42.923 |
| Weeks 58-60 | 59.54 ± 45.249 | 46.44 ± 44.871 | 70.83 ± 40.675 |
| Weeks 68-70 | 62.42 ± 42.359 | 63.21 ± 43.450 | 64.35 ± 44.147 |
| Weeks 71-72 | 60.18 ± 41.743 | 60.74 ± 43.254 | 71.45 ± 41.406 |
| Weeks 73-76 | 33.22 ± 52.059 | 66.81 ± 30.298 | 76.90 ± 34.724 |
A positive pruritus assessment was defined as a scratching score of \<=1 or at least a 1-point drop from baseline on the Albireo ObsRO instrument. The percentage of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments in the time interval recorded by each participant multiplied by 100. PM score represents daytime itching/scratching and tiredness.
| percentage of assessments | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 1-4 | 49.01 ± 35.687 | 24.13 ± 30.344 | 62.08 ± 34.404 |
| Weeks 5-8 | 60.03 ± 39.300 | 30.45 ± 35.987 | 73.11 ± 36.284 |
| Weeks 9-12 | 57.77 ± 42.435 | 31.73 ± 38.223 | 72.42 ± 37.687 |
| Weeks 13-16 | 61.36 ± 41.530 | 33.08 ± 39.999 | 74.13 ± 38.607 |
| Weeks 17-20 | 56.49 ± 41.590 | 36.22 ± 41.689 | 76.12 ± 36.907 |
| Weeks 21-24 | 55.78 ± 43.495 | 36.28 ± 41.318 | 77.23 ± 37.626 |
| Weeks 34-36 | 58.75 ± 39.774 | 30.28 ± 39.297 | 75.11 ± 36.650 |
| Weeks 44-46 | 67.01 ± 39.601 | 38.02 ± 43.252 | 81.00 ± 30.974 |
| Weeks 47-48 | 71.08 ± 41.878 | 34.98 ± 43.148 | 74.62 ± 38.856 |
| Weeks 58-60 | 72.28 ± 38.149 | 43.53 ± 43.694 | 73.17 ± 38.473 |
| Weeks 68-70 | 62.63 ± 40.626 | 55.65 ± 42.883 | 74.85 ± 38.702 |
| Weeks 71-72 | 55.12 ± 42.336 | 53.97 ± 45.611 | 75.38 ± 39.038 |
| Weeks 73-76 | 49.36 ± 36.671 | 63.35 ± 31.538 | 72.94 ± 32.765 |
A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change of 1.0 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction against the threshold value of 1.0 based on bi-weekly scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. The data reported represent the combination of pruritus assessments from both AM and PM scores.
| percentage of participants | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 1-2 | 15.8 (3.38 to 39.58) | 2.8 (0.07 to 14.53) | 28.3 (16.79 to 42.35) |
| Weeks 3-4 | 36.8 (16.29 to 61.64) | 2.8 (0.07 to 14.53) | 52.8 (38.64 to 66.70) |
| Weeks 5-6 | 36.8 (16.29 to 61.64) | 5.6 (0.68 to 18.66) | 55.8 (41.33 to 69.53) |
| Weeks 7-8 | 36.8 (16.29 to 61.64) | 13.9 (4.67 to 29.50) | 54.9 (40.34 to 68.87) |
| Weeks 9-10 | 31.6 (12.58 to 56.55) | 8.3 (1.75 to 22.47) | 58.0 (43.21 to 71.81) |
| Weeks 11-12 | 33.3 (13.34 to 59.01) | 13.9 (4.67 to 29.50) | 56.0 (41.25 to 70.01) |
| Weeks 13-14 | 50.0 (26.02 to 73.98) | 11.1 (3.11 to 26.06) | 58.0 (43.21 to 71.81) |
| Weeks 15-16 | 50.0 (26.02 to 73.98) | 13.9 (4.67 to 29.50) | 57.1 (42.21 to 71.18) |
| Weeks 17-18 | 44.4 (21.53 to 69.24) | 16.7 (6.37 to 32.81) | 55.3 (40.12 to 69.83) |
| Weeks 19-20 | 50.0 (24.65 to 75.35) | 22.2 (10.12 to 39.15) | 56.3 (41.18 to 70.52) |
| Weeks 21-22 | 41.2 (18.44 to 67.08) | 16.7 (6.37 to 32.81) | 57.8 (42.15 to 72.34) |
| Weeks 23-24 | 41.2 (18.44 to 67.08) | 19.4 (8.19 to 36.02) | 56.5 (41.11 to 71.07) |
| Weeks 35-36 | 33.3 (11.82 to 61.62) | 18.5 (6.30 to 38.08) | 56.4 (39.62 to 72.19) |
| Weeks 47-48 | 57.1 (28.86 to 82.34) | 25.0 (10.69 to 44.87) | 64.1 (47.18 to 78.80) |
| Weeks 59-60 | 36.4 (10.93 to 69.21) | 30.0 (14.73 to 49.40) | 60.0 (40.60 to 77.34) |
| Weeks 71-72 | 41.7 (15.17 to 72.33) | 34.6 (17.21 to 55.67) | 61.3 (42.19 to 78.15) |
A responder is defined as a participant who reports a decrease in pruritus score from unrounded baseline equivalent to or greater than the threshold of meaningful change of 1.0 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction against the thresholds value of 1.0 based on monthly scores. ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with score from 0 to 4 where 0 is no scratching and 4 is worst possible scratching. The data reported represent the combination of pruritus assessments from both AM and PM scores.
| percentage of participants | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 1-4 | 21.1 (6.05 to 45.57) | 2.8 (0.07 to 14.53) | 43.4 (29.84 to 57.72) |
| Weeks 5-8 | 36.8 (16.29 to 61.64) | 8.3 (1.75 to 22.47) | 54.9 (40.34 to 68.87) |
| Weeks 9-12 | 36.8 (16.29 to 61.64) | 11.1 (3.11 to 26.06) | 56.0 (41.25 to 70.01) |
| Weeks 13-16 | 50.0 (26.02 to 73.98) | 13.9 (4.67 to 29.50) | 60.0 (45.18 to 73.59) |
| Weeks 17-20 | 38.9 (17.30 to 64.25) | 16.7 (6.37 to 32.81) | 56.3 (41.18 to 70.52) |
| Weeks 21-24 | 35.3 (14.21 to 61.67) | 16.7 (6.37 to 32.81) | 53.3 (37.87 to 68.34) |
| Weeks 34-36 | 43.8 (19.75 to 70.12) | 23.3 (9.93 to 42.28) | 58.1 (42.13 to 72.99) |
| Weeks 45-48 | 53.3 (26.59 to 78.73) | 24.1 (10.30 to 43.54) | 64.1 (47.18 to 78.80) |
| Weeks 58-60 | 46.2 (19.22 to 74.87) | 29.0 (14.22 to 48.04) | 57.1 (39.35 to 73.68) |
| Weeks 68-72 | 53.8 (25.13 to 80.78) | 37.5 (18.80 to 59.41) | 64.5 (45.37 to 80.77) |
The percentage of participants who achieved positive pruritus assessment for more than 50% of the time for Weeks 0-72 is reported. A positive pruritus assessment is defined as a scratching score of \<=1 or at least a 1-point decrease from baseline on the Albireo ObsRO instrument based on rounded baseline and was calculated based on reported eDiary data. At each assessment, the AM score was compared to the baseline AM average, and the PM score was compared to the baseline PM average. The data reported represent the combination of pruritus assessments from both AM and PM scores.
| percentage of participants | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Percentage of Participants Achieving a Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO (Combined AM and PM Scores) | 58.3 (27.67 to 84.83) | 34.6 (17.21 to 55.67) | 83.9 (66.27 to 94.55) |
Participants who underwent BDS and/or liver transplantation are reported.
| Participants | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Weeks 0-24: BDS | 0 | 0 | 0 |
| Weeks 0-24: Liver Transplantation | 1 | 0 | 0 |
| Weeks 0-24: Liver Transplantation or BDS | 1 | 0 | 0 |
| Weeks 0-48: BDS | 1 | 0 | 1 |
| Weeks 0-48: Liver Transplantation | 2 | 0 | 2 |
| Weeks 0-48: Liver Transplantation or BDS | 3 | 0 | 3 |
| Weeks 0-72: BDS | 1 | 0 | 1 |
| Weeks 0-72: Liver Transplantation | 2 | 0 | 5 |
| Weeks 0-72: Liver Transplantation or BDS | 3 | 0 | 6 |
| Weeks 0-88: BDS | 1 | 0 | 1 |
| Weeks 0-88: Liver Transplantation | 2 | 1 | 6 |
| Weeks 0-88: Liver Transplantation or BDS | 3 | 1 | 7 |
| Weeks 0-104: BDS | 1 | 0 | 1 |
| Weeks 0-104: Liver Transplantation | 2 | 2 | 7 |
| Weeks 0-104: Liver Transplantation or BDS | 3 | 2 | 8 |
| Weeks 0-120: BDS | 1 | 0 | 1 |
| Weeks 0-120: Liver Transplantation | 3 | 2 | 9 |
| Weeks 0-120: Liver Transplantation or BDS | 4 | 2 | 10 |
| Weeks 0-136: BDS | 1 | 0 | 1 |
| Weeks 0-136: Liver Transplantation | 3 | 3 | 9 |
| Weeks 0-136: Liver Transplantation or BDS | 4 | 3 | 10 |
| Weeks 0-152: BDS | 1 | 1 | 1 |
| Weeks 0-152: Liver Transplantation | 3 | 3 | 9 |
| Weeks 0-152: Liver Transplantation or BDS | 4 | 4 | 10 |
| Weeks 0-168: BDS | 1 | 1 | 1 |
| Weeks 0-168: Liver Transplantation | 4 | 3 | 9 |
| Weeks 0-168: Liver Transplantation or BDS | 5 | 4 | 10 |
| Weeks 0-184: BDS | 1 | 1 | 1 |
| Weeks 0-184: Liver Transplantation | 4 | 3 | 9 |
| Weeks 0-184: Liver Transplantation or BDS | 5 | 4 | 10 |
| Weeks 0-200: BDS | 1 | 1 | 1 |
| Weeks 0-200: Liver Transplantation | 4 | 3 | 10 |
| Weeks 0-200: Liver Transplantation or BDS | 5 | 4 | 11 |
| Weeks 0-216: BDS | 1 | 2 | 1 |
| Weeks 0-216: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-216: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-232: BDS | 1 | 2 | 1 |
| Weeks 0-232: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-232: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-248: BDS | 1 | 2 | 1 |
| Weeks 0-248: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-248: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-264: BDS | 1 | 2 | 1 |
| Weeks 0-264: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-264: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-280: BDS | 1 | 2 | 1 |
| Weeks 0-280: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-280: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-296: BDS | 1 | 2 | 1 |
| Weeks 0-296: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-296: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-312: BDS | 1 | 2 | 1 |
| Weeks 0-312: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-312: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-328: BDS | 1 | 2 | 1 |
| Weeks 0-328: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-328: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-344: BDS | 1 | 2 | 1 |
| Weeks 0-344: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-344: Liver Transplantation or BDS | 5 | 5 | 11 |
| Weeks 0-360: BDS | 1 | 2 | 1 |
| Weeks 0-360: Liver Transplantation | 4 | 4 | 10 |
| Weeks 0-360: Liver Transplantation or BDS | 5 | 5 | 11 |
Height was measured using certified stadiometer. Change in growth parameters was assessed using linear growth (height) compared to standard growth curve (Z-score) calculated by using the software or methods from the Centers for Disease Control (CDC) website for participants with age \>=2 years old and from the World Health Organization (WHO) website for participants with age \<2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to first dose of study treatment in the A4250-008 study. A Z-score indicates how many standard deviation's (SD) a participant's height measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below average a measurement was.
| Z-score | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Week 12 | 0.168 (-0.52 to 1.71) | 0.326 (-1.32 to 1.74) | 0.024 (-0.96 to 1.59) |
| Week 24 | 0.181 (-0.28 to 1.53) | 0.341 (-1.04 to 2.26) | 0.089 (-1.34 to 1.97) |
| Week 36 | 0.235 (-0.34 to 1.16) | 0.435 (-1.70 to 2.17) | 0.108 (-0.86 to 1.55) |
| Week 48 | 0.485 (0.02 to 1.42) | 0.662 (-0.75 to 2.08) | 0.095 (-1.46 to 2.03) |
| Week 60 | 0.369 (-0.09 to 1.79) | 0.674 (-0.66 to 2.37) | 0.038 (-2.29 to 2.68) |
| Average of Weeks 70-72 | 0.556 (-0.01 to 1.57) | 0.543 (-0.83 to 2.12) | 0.224 (-1.42 to 2.62) |
| Week 88 | 0.294 (-0.28 to 1.62) | 0.751 (-0.30 to 2.19) | 0.320 (-2.06 to 3.15) |
| Week 104 | 0.258 (-0.44 to 1.65) | 0.772 (-0.20 to 2.40) | 0.291 (-1.93 to 3.05) |
| Week 120 | 0.206 (-0.45 to 1.71) | 0.679 (-0.22 to 1.72) | 0.313 (-1.79 to 2.79) |
| Week 136 | 0.045 (-0.47 to 1.63) | 0.784 (-0.51 to 1.75) | 0.304 (-1.87 to 2.81) |
| Week 152 | 0.104 (-0.39 to 1.55) | 0.698 (-0.50 to 1.68) | 0.299 (-2.37 to 2.97) |
| Week 168 | 0.193 (-0.62 to 1.39) | 0.564 (-0.53 to 1.61) | 0.381 (-2.39 to 2.84) |
| Week 184 | 0.170 (-0.51 to 1.55) | 0.448 (-0.91 to 1.97) | 0.083 (-2.19 to 3.06) |
| Week 200 | 0.279 (-0.54 to 1.45) | 0.512 (-0.31 to 1.57) | 0.287 (-2.29 to 2.99) |
| Week 216 | 0.382 (-0.36 to 1.48) | 0.042 (-0.54 to 1.85) | 0.351 (-2.28 to 0.88) |
| Week 232 | 0.442 (0.26 to 1.44) | 0.280 (-0.28 to 1.65) | 0.495 (0.18 to 0.82) |
| Week 248 | 1.23 (1.23 to 1.23) | 0.255 (-0.87 to 1.36) | 0.540 (0.49 to 0.98) |
| Week 264 | — | 0.223 (-0.91 to 1.43) | 0.617 (0.53 to 0.69) |
| Week 280 | 1.070 (1.07 to 1.07) | 0.052 (-0.72 to 1.51) | 0.764 (0.54 to 0.99) |
| Week 296 | — | -0.052 (-0.88 to 1.65) | 0.45 (0.45 to 0.45) |
| Week 312 | — | -0.158 (-0.79 to 1.40) | 0.38 (0.38 to 0.38) |
| Week 328 | — | -0.25 (-0.25 to -0.25) | — |
Weight was measured using certified weight scale. Change in growth parameters was assessed using linear growth (weight) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age \>=2 years old and from the WHO website for participants with age \<2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. The Z-score indicates how many SDs a participant's weight measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was.
| Z-score | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Week 12 | 0.139 (-0.56 to 0.75) | 0.098 (-0.85 to 1.51) | 0.037 (-0.91 to 1.25) |
| Week 24 | 0.155 (-0.49 to 1.40) | 0.383 (-0.75 to 1.57) | 0.169 (-0.68 to 1.74) |
| Week 36 | 0.422 (-0.53 to 1.91) | 0.427 (-1.09 to 2.02) | 0.210 (-0.78 to 1.69) |
| Week 48 | 0.544 (-1.15 to 1.43) | 0.494 (-1.04 to 2.14) | 0.246 (-0.54 to 1.29) |
| Week 60 | 0.305 (-0.35 to 2.42) | 0.291 (-1.75 to 2.31) | 0.208 (-1.21 to 1.97) |
| Average of Weeks 70-72 | 0.098 (-1.13 to 2.17) | 0.389 (-1.21 to 2.11) | 0.400 (-0.86 to 2.27) |
| Week 88 | 0.174 (-0.35 to 2.05) | 0.648 (-1.25 to 2.74) | 0.149 (-0.48 to 2.25) |
| Week 104 | 0.060 (-0.44 to 2.33) | 0.637 (-0.40 to 2.49) | 0.474 (-2.49 to 2.35) |
| Week 120 | 0.018 (-0.47 to 2.23) | 0.287 (-0.78 to 2.34) | 0.210 (-1.41 to 2.06) |
| Week 136 | 0.155 (-0.46 to 2.54) | 0.378 (-0.81 to 2.48) | 0.243 (-1.37 to 2.21) |
| Week 152 | -0.079 (-0.83 to 2.21) | 0.215 (-0.86 to 2.21) | 0.359 (-1.16 to 2.19) |
| Week 168 | 0.096 (-0.90 to 1.15) | 0.074 (-1.04 to 2.32) | 0.177 (-1.16 to 2.15) |
| Week 184 | -0.017 (-0.69 to 2.02) | 0.265 (-0.78 to 2.16) | 0.227 (-1.46 to 2.15) |
| Week 200 | 0.027 (-0.62 to 1.21) | 0.374 (-0.56 to 2.32) | 0.191 (-1.34 to 2.04) |
| Week 216 | -0.074 (-1.08 to 0.98) | 0.076 (-0.97 to 1.89) | -0.242 (-1.25 to 0.89) |
| Week 232 | 0.088 (-0.66 to 0.29) | -0.089 (-1.07 to 1.77) | -0.333 (-1.35 to 1.01) |
| Week 248 | 0.350 (0.35 to 0.35) | -0.536 (-1.41 to 1.93) | -0.070 (-0.42 to 0.81) |
| Week 264 | — | -0.381 (-1.18 to 2.24) | 0.330 (-0.26 to 0.92) |
| Week 280 | 0.17 (0.17 to 0.17) | -0.173 (-1.36 to 1.79) | 0.533 (-0.08 to 1.15) |
| Week 296 | — | -0.280 (-1.64 to 0.58) | 1.22 (1.22 to 1.22) |
| Week 312 | — | -0.522 (-1.31 to 0.01) | 1.23 (1.23 to 1.23) |
| Week 328 | — | -0.87 (-0.87 to -0.87) | — |
BMI was calculated by weight (kg) / height (m)\^2 which were measured by the standardized assessments. Change in growth parameters was assessed using linear growth (BMI) compared to standard growth curve (Z-score), calculated by using the software or methods from the CDC website for participants with age \>=2 years old and from the WHO website for participants with age \<2 years old. A Z-score was not calculated for participants whose accurate age was not available. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. The Z-score indicates how many SDs a participant's BMI measurement, was from the average for their age and sex. A Z-score of 0 represents the median or 50th percentile, while positive or negative values show how far above or below the average a measurement was.
| Z-score | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Week 12 | -0.082 (-1.55 to 1.11) | -0.160 (-1.99 to 2.57) | 0.032 (-1.07 to 1.89) |
| Week 24 | -0.106 (-0.66 to 1.86) | 0.150 (-2.00 to 2.21) | 0.202 (-1.60 to 2.08) |
| Week 36 | 0.132 (-1.26 to 2.22) | -0.076 (-1.07 to 2.48) | 0.360 (-1.43 to 2.29) |
| Week 48 | 0.028 (-0.88 to 1.23) | -0.135 (-2.44 to 2.59) | 0.129 (-1.34 to 2.45) |
| Week 60 | -0.152 (-0.61 to 3.59) | -0.315 (-1.85 to 2.37) | 0.218 (-1.92 to 3.15) |
| Average of Weeks 70-72 | -0.059 (-1.24 to 3.12) | -0.007 (-1.64 to 2.25) | 0.182 (-0.99 to 2.68) |
| Week 88 | -0.130 (-0.76 to 2.65) | 0.202 (-1.55 to 2.99) | 0.101 (-1.10 to 2.41) |
| Week 104 | -0.031 (-0.91 to 3.45) | 0.001 (-1.45 to 2.08) | 0.382 (-1.59 to 2.18) |
| Week 120 | -0.175 (-1.12 to 3.18) | -0.295 (-1.51 to 2.20) | 0.078 (-2.12 to 2.17) |
| Week 136 | 0.152 (-0.96 to 3.85) | -0.047 (-1.75 to 1.75) | 0.148 (-1.29 to 2.56) |
| Week 152 | -0.458 (-1.39 to 3.55) | -0.428 (-1.35 to 2.02) | 0.076 (-1.32 to 2.81) |
| Week 168 | -0.191 (-1.66 to 2.31) | -0.120 (-1.21 to 1.85) | 0.052 (-1.53 to 2.59) |
| Week 184 | -0.087 (-1.60 to 0.83) | -0.067 (-1.82 to 2.17) | 0.358 (-1.59 to 2.44) |
| Week 200 | -0.482 (-1.24 to 0.10) | 0.176 (-1.49 to 2.30) | 0.214 (-1.45 to 2.19) |
| Week 216 | -0.649 (-2.35 to -0.19) | 0.058 (-2.89 to 2.02) | -0.521 (-1.44 to 1.72) |
| Week 232 | -0.774 (-1.84 to -0.67) | -0.598 (-2.21 to 1.92) | -1.023 (-1.39 to 1.19) |
| Week 248 | -0.54 (-0.54 to -0.54) | -0.832 (-1.73 to 2.00) | -0.671 (-2.06 to 1.03) |
| Week 264 | — | -0.397 (-1.71 to 2.30) | 0.037 (-1.07 to 1.14) |
| Week 280 | -0.71 (-0.71 to -0.71) | -0.693 (-1.84 to 2.12) | 0.143 (-1.12 to 1.40) |
| Week 296 | — | -0.702 (-1.72 to 0.36) | 1.50 (1.50 to 1.50) |
| Week 312 | — | -1.115 (-1.95 to -0.15) | 1.52 (1.52 to 1.52) |
| Week 328 | — | -0.87 (-0.87 to -0.87) | — |
The number of participants with use of UDCA and/or rifampicin are reported.
| Participants | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Week 24: Use of UDCA | 17 | 29 | 43 |
| Week 24: Use of Rifampicin | 17 | 19 | 37 |
| Week 24: Use of UDCA or Rifampicin | 19 | 33 | 50 |
| Week 24: Use of UDCA and Rifampicin | 15 | 15 | 30 |
| Week 48: Use of UDCA | 16 | 27 | 39 |
| Week 48: Use of Rifampicin | 16 | 20 | 31 |
| Week 48: Use of UDCA or Rifampicin | 18 | 33 | 46 |
| Week 48: Use of UDCA and Rifampicin | 14 | 14 | 24 |
| Week 72: Use of UDCA | 14 | 24 | 34 |
| Week 72: Use of Rifampicin | 14 | 15 | 26 |
| Week 72: Use of UDCA or Rifampicin | 16 | 29 | 41 |
| Week 72: Use of UDCA and Rifampicin | 12 | 10 | 19 |
The PELD score was calculated for children under 12 years of age, ranged across negative to positive values. Calculation of PELD score was done by converting the laboratory parameters: total bilirubin in milligram/deciliter (mg/dL), albumin in gram (g)/dL, and creatinine in mg/dL laboratory parameters were converted to units. PELD score was calculated as 4.80\*ln (total bilirubin)+18.57\*ln \[international normalized ratio (INR)\] - 6.87\*ln (albumin) + 4.36 (if participant \<1 year: scores for participants listed for liver transplantation before the participant's first birthday continued to include the value assigned for age (\<1 year) until the participant reached the age of 24 months)+6.67 (if the participant has growth failure \[\<-2 SD\]). The laboratory values \<1.0 were set to 1.0 for the calculation of PELD score. Lower scores represent less severe hepatic disease. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
| score on a scale | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Week 72 | -0.397 ± 3.6168 | 1.361 ± 2.5083 | -0.303 ± 9.4631 |
| Week 88 | -0.162 ± 4.3698 | 1.663 ± 2.6453 | -2.505 ± 5.5626 |
| Week 104 | 1.409 ± 2.4744 | 1.159 ± 2.8118 | -1.761 ± 5.7946 |
| Week 120 | 1.290 ± 2.0085 | 1.043 ± 3.1973 | -1.808 ± 6.7304 |
| Week 136 | 1.931 ± 4.1746 | 0.949 ± 3.7434 | -1.719 ± 6.4893 |
| Week 152 | 3.650 ± 4.1947 | 0.775 ± 3.8588 | -1.289 ± 6.2775 |
| Week 168 | 1.176 ± 2.0719 | 2.242 ± 3.6302 | -1.824 ± 7.5102 |
| Week 184 | 2.202 ± 4.5430 | 0.932 ± 1.9967 | 0.714 ± 9.0279 |
| Week 200 | -1.030 ± 1.8076 | 1.005 ± 1.9098 | 0.281 ± 11.0640 |
| Week 216 | 0.348 ± 1.6231 | 0.367 ± 1.8186 | -1.466 ± 1.8539 |
| Week 232 | 1.354 ± 3.3160 | 0.629 ± 1.2947 | -1.173 ± 1.8322 |
| Week 248 | 1.776 ± 3.1998 | 2.375 ± 3.2904 | -1.561 ± 2.6707 |
| Week 264 | — | 2.030 ± 4.9448 | 0.000 ± NA |
| Week 280 | — | 0.014 ± 1.5680 | -3.450 ± NA |
| Week 296 | — | 6.052 ± 10.1940 | — |
| Week 312 | — | 0.059 ± 0.9471 | -3.450 ± NA |
MELD score was calculated for children 12 years of age or older ranges from 6 to 40. Calculation of MELD score was done by converting the laboratory parameters in the following units: total bilirubin in mg/dL, albumin in g/dL, and creatinine in mg/dL laboratory parameters were converted to units. MELD score was calculated as 9.57\*ln (creatinine)+3.78\*ln (total bilirubin)+11.2 \*ln (INR)+6.43. Laboratory values \<1.0 were set to 1.0 and serum creatinine values \>4.0 mg/dL were set to 4.0 for calculation of the MELD score. Lower scores represent less severe hepatic disease. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study. All assessments after intercurrent events (premature treatment discontinuation, death, or initiation of rescue treatments such as biliary diversion surgery or liver transplantation) or follow-up assessments (\>= last dose day+15 days) were excluded from analysis.
| score on a scale | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Baseline | 6.869 ± NA | 9.795 ± 2.4694 | 11.574 ± 4.0801 |
| Week 72 | — | 1.286 ± NA | -2.221 ± 5.7744 |
| Week 88 | — | — | 6.182 ± 1.4067 |
| Week 104 | — | — | 6.425 ± NA |
| Week 120 | — | — | 4.983 ± NA |
The AST to APRI score was calculated as \[(AST in units per liter {U/L})/ (AST upper limit of normal {ULN} in U/L)\] \* 100/ (platelets in 10\^9/L). The APRI score is a way to assess fibrosis of the liver. The lower the APRI score (\< 0.5), the greater the negative predictive value and ability to rule out cirrhosis; the higher the value (\> 1.5) the greater the positive predictive value and ability to rule in cirrhosis. Lower values indicate less severe hepatic fibrosis. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
| score on a scale | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Change From Baseline to Week 72 in Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) Score | 0.044 ± 0.3435 | 0.071 ± 0.3951 | 0.411 ± 0.9690 |
Fib-4 score was calculated as (age \* AST in U/L)/ (platelets in 10\^9/L \*√ ( alanine aminotransferase \[ALT\] in U/L). The FIB-4 score estimates the amount of scarring in the liver. A FIB-4 score \<1.45 has a negative predictive value of 90% for advanced fibrosis (Ishak fibrosis score 4-6 which includes early bridging fibrosis to cirrhosis). In contrast, a FIB-4 score \> 3.25 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis. Lower values indicate less severe hepatic fibrosis. Baseline was the last available assessment prior to the first dose of study treatment in the A4250-008 study.
| score on a scale | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Change From Baseline to Week 72 in Fibrosis-4 (Fib-4) Score | 0.050 ± 0.1187 | 0.106 ± 0.2696 | 0.113 ± 0.2820 |
Collected over Treatment emergent serious adverse event (TESAEs) and non-serious treatment emergent adverse event (TEAEs) were collected from the start of study treatment administration (Day 1) up to end of the study approximately 330 weeks. All-cause mortality (death) was assessed from signing of the first informed consent form until end of the study, approximately 374 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: Placebo/Odevixibat | 0/19 (0%) | 5/19 (26.3%) | 18/19 (94.7%) |
| Cohort 1: Odevixibat/Odevixibat | 0/37 (0%) | 7/37 (18.9%) | 35/37 (94.6%) |
| Cohort 2: Odevixibat | 0/60 (0%) | 27/60 (45%) | 57/60 (95%) |
| Event | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| HaemolysisBlood and lymphatic system disorders | 1/19 | 0/37 | 0/60 |
| CholestasisHepatobiliary disorders | 1/19 | 0/37 | 0/60 |
| Chronic hepatic failureHepatobiliary disorders | 1/19 | 0/37 | 0/60 |
| HyperbilirubinaemiaHepatobiliary disorders | 1/19 | 0/37 | 0/60 |
| Gastroenteritis viralInfections and infestations | 1/19 | 0/37 | 0/60 |
| Pseudomonal sepsisInfections and infestations | 1/19 | 0/37 | 0/60 |
| Viral upper respiratory tract infectionInfections and infestations | 1/19 | 0/37 | 0/60 |
| Haemoglobin decreasedInvestigations | 1/19 | 0/37 | 0/60 |
| Device dislocationProduct Issues | 1/19 | 0/37 | 0/60 |
| CoagulopathyBlood and lymphatic system disorders | 0/19 | 0/37 | 2/60 |
| Event | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat |
|---|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 8/19 | 11/37 | 12/60 |
| PyrexiaGeneral disorders | 7/19 | 12/37 | 16/60 |
| CoughRespiratory, thoracic and mediastinal disorders | 4/19 | 13/37 | 10/60 |
| NasopharyngitisInfections and infestations | 3/19 | 10/37 | 10/60 |
| Blood bilirubin increasedInvestigations | 5/19 | 10/37 | 15/60 |
| DiarrhoeaGastrointestinal disorders | 2/19 | 8/37 | 16/60 |
| COVID-19Infections and infestations | 3/19 | 3/37 | 15/60 |
| InfluenzaInfections and infestations | 0/19 | 7/37 | 9/60 |
| PruritusSkin and subcutaneous tissue disorders | 3/19 | 7/37 | 7/60 |
| International normalised ratio increasedInvestigations | 3/19 | 6/37 | 11/60 |
The Full Analysis Set (FAS) consisted of all participants who received at least 1 dose of study treatment in study A4250-008.
| Age, Continuous(years) | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat | Total |
|---|---|---|---|---|
| Mean | 4.34 ± 3.962 | 4.75 ± 3.711 | 7.62 ± 7.208 | 6.17 ± 5.977 |
| Sex: Female, Male(Participants) | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat | Total |
|---|---|---|---|---|
| Female | 7 | 20 | 25 | 52 |
| Male | 12 | 17 | 35 | 64 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 2 | 3 |
| Not Hispanic or Latino | 18 | 37 | 50 | 105 |
| Unknown or Not Reported | 0 | 0 | 8 | 8 |
| Race/Ethnicity, Customized(Participants) | Cohort 1: Placebo/Odevixibat | Cohort 1: Odevixibat/Odevixibat | Cohort 2: Odevixibat | Total |
|---|---|---|---|---|
| White | 16 | 31 | 53 | 100 |
| Black/African American | 0 | 1 | 2 | 3 |
| Asian | 2 | 3 | 2 | 7 |
| Other | 1 | 2 | 3 | 6 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
Time frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
Access criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
Data sharing details ↗ · vivli.org
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Studies of the drug tested here: Odevixibat
Cholestasis, progressive familial intrahepatic 1 →