Trial Outcomes & Findings for Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC (NCT NCT03659916)

Last Updated: 2026-02-03

Results Overview

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 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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

116 participants

Primary outcome timeframe

Baseline and Week 72

Results posted on

2026-02-03

Participant Flow

This Phase III, open-label extension was conducted in participants with progressive familial intrahepatic cholestasis (PFIC) at 43 centers in 13 countries (Belgium, France, Germany, Italy, Netherlands, Poland, United Kingdom, United States \[US\], Australia, Canada, Israel, Saudi Arabia, and Turkey). The first participant was enrolled on 28 September 2018 and data cut-off (DCO) date was 15 February 2024.

This study consisted of a 72-week treatment period and a 4-week follow-up period. An optional extension period for continued treatment until commercial availability of odevixibat followed the 72-week treatment period. A total of 116 participants were enrolled in the study. Results are presented up to DCO of 15 February 2024.

Participant milestones

Participant milestones
Measure	Cohort 1: Placebo/Odevixibat Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Treatment Period (72 Weeks) STARTED	19	37	60
Treatment Period (72 Weeks) COMPLETED	15	28	40
Treatment Period (72 Weeks) NOT COMPLETED	4	9	20
Optional Extension Treatment (176 Weeks) STARTED	14	27	33
Optional Extension Treatment (176 Weeks) COMPLETED	0	0	0
Optional Extension Treatment (176 Weeks) NOT COMPLETED	14	27	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Placebo/Odevixibat Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 microgram/kilogram/day (mcg/kg/day) for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Treatment Period (72 Weeks) Adverse Event	2	1	6
Treatment Period (72 Weeks) Withdrawal by Subject	1	4	4
Treatment Period (72 Weeks) Physician Decision	0	1	0
Treatment Period (72 Weeks) Lost to Follow-up	0	0	1
Treatment Period (72 Weeks) Other	1	3	9
Optional Extension Treatment (176 Weeks) Adverse Event	0	0	1
Optional Extension Treatment (176 Weeks) Withdrawal by Subject	0	1	0
Optional Extension Treatment (176 Weeks) Physician Decision	0	0	1
Optional Extension Treatment (176 Weeks) Transition to Commercial Drug	5	17	11
Optional Extension Treatment (176 Weeks) Other	4	0	3
Optional Extension Treatment (176 Weeks) Ongoing Optional Extension Period	5	9	17

Baseline Characteristics

Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=37 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=60 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.	Total n=116 Participants Total of all reporting groups
Age, Continuous	4.34 years STANDARD_DEVIATION 3.962 • n=13 Participants	4.75 years STANDARD_DEVIATION 3.711 • n=15 Participants	7.62 years STANDARD_DEVIATION 7.208 • n=28 Participants	6.17 years STANDARD_DEVIATION 5.977 • n=2 Participants
Sex: Female, Male Female	7 Participants n=13 Participants	20 Participants n=15 Participants	25 Participants n=28 Participants	52 Participants n=2 Participants
Sex: Female, Male Male	12 Participants n=13 Participants	17 Participants n=15 Participants	35 Participants n=28 Participants	64 Participants n=2 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=13 Participants	0 Participants n=15 Participants	2 Participants n=28 Participants	3 Participants n=2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=13 Participants	37 Participants n=15 Participants	50 Participants n=28 Participants	105 Participants n=2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=15 Participants	8 Participants n=28 Participants	8 Participants n=2 Participants
Race/Ethnicity, Customized White	16 Participants n=13 Participants	31 Participants n=15 Participants	53 Participants n=28 Participants	100 Participants n=2 Participants
Race/Ethnicity, Customized Black/African American	0 Participants n=13 Participants	1 Participants n=15 Participants	2 Participants n=28 Participants	3 Participants n=2 Participants
Race/Ethnicity, Customized Asian	2 Participants n=13 Participants	3 Participants n=15 Participants	2 Participants n=28 Participants	7 Participants n=2 Participants
Race/Ethnicity, Customized Other	1 Participants n=13 Participants	2 Participants n=15 Participants	3 Participants n=28 Participants	6 Participants n=2 Participants

PRIMARY outcome

Timeframe: Baseline and Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=15 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=28 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=43 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline in Serum Bile Acids	-104.00 micromole per liter (µmol/L) Standard Deviation 167.318	-139.84 micromole per liter (µmol/L) Standard Deviation 172.070	-57.97 micromole per liter (µmol/L) Standard Deviation 137.990

PRIMARY outcome

Timeframe: Baseline and Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.

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 proportion of positive pruritus assessment was calculated as the number of positive pruritus assessments divided by the total number of reported assessments only when more than 50% of planned assessment recorded by each participant.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=12 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=26 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=31 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Proportion of Positive Pruritus Assessments at the Participant Level Over 72-Week Using the Albireo Observer-Reported Outcome (ObsRo) Instrument	55.20 proportion of pruritus-participant-level Standard Deviation 38.733	38.58 proportion of pruritus-participant-level Standard Deviation 34.877	77.28 proportion of pruritus-participant-level Standard Deviation 28.084

SECONDARY outcome

Timeframe: 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

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=37 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=53 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Proportion 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 Weeks 0 - 12	51.05 proportion of pruritus-participant-level Standard Deviation 37.670	27.34 proportion of pruritus-participant-level Standard Deviation 28.687	67.63 proportion of pruritus-participant-level Standard Deviation 33.645
Proportion 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 Weeks 0 - 24	56.00 proportion of pruritus-participant-level Standard Deviation 38.331	31.45 proportion of pruritus-participant-level Standard Deviation 32.324	68.55 proportion of pruritus-participant-level Standard Deviation 34.116
Proportion 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 Weeks 0 - 46	60.41 proportion of pruritus-participant-level Standard Deviation 39.491	34.70 proportion of pruritus-participant-level Standard Deviation 35.593	75.46 proportion of pruritus-participant-level Standard Deviation 29.801
Proportion 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 Weeks 0 - 48	61.61 proportion of pruritus-participant-level Standard Deviation 39.936	33.56 proportion of pruritus-participant-level Standard Deviation 35.668	74.79 proportion of pruritus-participant-level Standard Deviation 30.843
Proportion 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 Weeks 0 - 4	45.72 proportion of pruritus-participant-level Standard Deviation 34.300	23.64 proportion of pruritus-participant-level Standard Deviation 27.005	60.14 proportion of pruritus-participant-level Standard Deviation 33.985
Proportion 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 Weeks 0 - 22	56.01 proportion of pruritus-participant-level Standard Deviation 38.537	31.09 proportion of pruritus-participant-level Standard Deviation 31.859	70.05 proportion of pruritus-participant-level Standard Deviation 33.858
Proportion 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 Weeks 0 - 36	54.63 proportion of pruritus-participant-level Standard Deviation 38.243	33.66 proportion of pruritus-participant-level Standard Deviation 33.704	69.97 proportion of pruritus-participant-level Standard Deviation 33.872
Proportion 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 Weeks 0 - 60	57.80 proportion of pruritus-participant-level Standard Deviation 38.873	33.18 proportion of pruritus-participant-level Standard Deviation 34.935	74.89 proportion of pruritus-participant-level Standard Deviation 30.434
Proportion 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 Weeks 0 - 70	58.18 proportion of pruritus-participant-level Standard Deviation 38.766	40.59 proportion of pruritus-participant-level Standard Deviation 34.928	75.60 proportion of pruritus-participant-level Standard Deviation 29.514

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

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 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).

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=18 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=35 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=54 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 46	-166.05 µmol/L Standard Deviation 195.963	-156.88 µmol/L Standard Deviation 157.687	-63.80 µmol/L Standard Deviation 128.199
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 48	-145.65 µmol/L Standard Deviation 177.520	-121.73 µmol/L Standard Deviation 114.214	-57.90 µmol/L Standard Deviation 143.238
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 70	-149.02 µmol/L Standard Deviation 186.918	-146.43 µmol/L Standard Deviation 196.501	-50.08 µmol/L Standard Deviation 140.232
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 72	-101.31 µmol/L Standard Deviation 169.631	-123.44 µmol/L Standard Deviation 143.220	-52.39 µmol/L Standard Deviation 156.473
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 4	-115.76 µmol/L Standard Deviation 151.014	-118.78 µmol/L Standard Deviation 172.353	-76.92 µmol/L Standard Deviation 94.662
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 12	-98.39 µmol/L Standard Deviation 149.118	-109.90 µmol/L Standard Deviation 176.472	-65.01 µmol/L Standard Deviation 136.303
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 22	-138.67 µmol/L Standard Deviation 147.069	-125.18 µmol/L Standard Deviation 165.395	-73.24 µmol/L Standard Deviation 126.319
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 24	-112.96 µmol/L Standard Deviation 175.107	-133.52 µmol/L Standard Deviation 191.550	-65.37 µmol/L Standard Deviation 128.580
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Weeks 36	-129.41 µmol/L Standard Deviation 179.357	-114.19 µmol/L Standard Deviation 200.789	-60.90 µmol/L Standard Deviation 128.520
Change From Baseline in Serum Bile Acids at Weeks 4, 12, 22, 24, 36, 46, 48, 60, 70, and 72 Week 60	-86.46 µmol/L Standard Deviation 159.360	-133.17 µmol/L Standard Deviation 162.933	-43.31 µmol/L Standard Deviation 125.923

SECONDARY outcome

Timeframe: 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, 73-76

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=37 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=53 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Proportion 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, 73-76 Weeks 1-4	45.72 proportion of pruritus-participant-level Standard Deviation 34.300	23.64 proportion of pruritus-participant-level Standard Deviation 27.005	60.14 proportion of pruritus-participant-level Standard Deviation 33.985
Proportion 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, 73-76 Weeks 5-8	53.75 proportion of pruritus-participant-level Standard Deviation 39.894	28.76 proportion of pruritus-participant-level Standard Deviation 32.349	71.14 proportion of pruritus-participant-level Standard Deviation 34.866
Proportion 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, 73-76 Weeks 17-20	55.28 proportion of pruritus-participant-level Standard Deviation 41.441	36.15 proportion of pruritus-participant-level Standard Deviation 38.564	73.95 proportion of pruritus-participant-level Standard Deviation 38.051
Proportion 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, 73-76 Weeks 9-12	54.01 proportion of pruritus-participant-level Standard Deviation 41.345	29.64 proportion of pruritus-participant-level Standard Deviation 35.594	71.03 proportion of pruritus-participant-level Standard Deviation 36.961
Proportion 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, 73-76 Weeks 13-16	57.47 proportion of pruritus-participant-level Standard Deviation 42.420	31.78 proportion of pruritus-participant-level Standard Deviation 36.364	72.19 proportion of pruritus-participant-level Standard Deviation 39.221
Proportion 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, 73-76 Weeks 21-24	55.62 proportion of pruritus-participant-level Standard Deviation 42.927	35.83 proportion of pruritus-participant-level Standard Deviation 40.132	73.11 proportion of pruritus-participant-level Standard Deviation 37.875
Proportion 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, 73-76 Weeks 34-36	58.24 proportion of pruritus-participant-level Standard Deviation 41.117	32.79 proportion of pruritus-participant-level Standard Deviation 39.066	72.39 proportion of pruritus-participant-level Standard Deviation 35.581
Proportion 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, 73-76 Weeks 44-46	67.33 proportion of pruritus-participant-level Standard Deviation 39.242	38.40 proportion of pruritus-participant-level Standard Deviation 43.144	77.11 proportion of pruritus-participant-level Standard Deviation 31.712
Proportion 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, 73-76 Weeks 47-48	67.31 proportion of pruritus-participant-level Standard Deviation 43.702	34.71 proportion of pruritus-participant-level Standard Deviation 42.594	71.86 proportion of pruritus-participant-level Standard Deviation 39.020
Proportion 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, 73-76 Weeks 58-60	65.82 proportion of pruritus-participant-level Standard Deviation 40.745	44.22 proportion of pruritus-participant-level Standard Deviation 43.534	72.31 proportion of pruritus-participant-level Standard Deviation 38.008
Proportion 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, 73-76 Weeks 68-70	62.43 proportion of pruritus-participant-level Standard Deviation 40.321	56.79 proportion of pruritus-participant-level Standard Deviation 42.935	69.40 proportion of pruritus-participant-level Standard Deviation 39.034
Proportion 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, 73-76 Weeks 71-72	57.65 proportion of pruritus-participant-level Standard Deviation 39.797	55.75 proportion of pruritus-participant-level Standard Deviation 45.076	72.26 proportion of pruritus-participant-level Standard Deviation 38.680
Proportion 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, 73-76 Weeks 73-76	41.59 proportion of pruritus-participant-level Standard Deviation 39.923	63.48 proportion of pruritus-participant-level Standard Deviation 29.003	69.23 proportion of pruritus-participant-level Standard Deviation 33.797

SECONDARY outcome

Timeframe: 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

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=36 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=53 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 34-36	57.49 proportion of pruritus-participant-level Standard Deviation 43.512	34.80 proportion of pruritus-participant-level Standard Deviation 39.644	69.92 proportion of pruritus-participant-level Standard Deviation 37.610
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 1-4	42.38 proportion of pruritus-participant-level Standard Deviation 36.177	23.72 proportion of pruritus-participant-level Standard Deviation 29.373	58.19 proportion of pruritus-participant-level Standard Deviation 36.799
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 5-8	48.16 proportion of pruritus-participant-level Standard Deviation 42.655	27.70 proportion of pruritus-participant-level Standard Deviation 34.144	69.00 proportion of pruritus-participant-level Standard Deviation 38.199
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 9-12	50.57 proportion of pruritus-participant-level Standard Deviation 42.880	28.41 proportion of pruritus-participant-level Standard Deviation 37.802	68.96 proportion of pruritus-participant-level Standard Deviation 38.876
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 13-16	53.47 proportion of pruritus-participant-level Standard Deviation 43.689	31.70 proportion of pruritus-participant-level Standard Deviation 38.438	69.03 proportion of pruritus-participant-level Standard Deviation 41.902
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 17-20	53.94 proportion of pruritus-participant-level Standard Deviation 42.837	35.37 proportion of pruritus-participant-level Standard Deviation 40.673	71.30 proportion of pruritus-participant-level Standard Deviation 40.934
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 21-24	55.52 proportion of pruritus-participant-level Standard Deviation 44.798	35.15 proportion of pruritus-participant-level Standard Deviation 41.940	69.63 proportion of pruritus-participant-level Standard Deviation 40.353
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 44-46	67.07 proportion of pruritus-participant-level Standard Deviation 42.321	40.11 proportion of pruritus-participant-level Standard Deviation 43.580	73.62 proportion of pruritus-participant-level Standard Deviation 37.122
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 47-48	63.67 proportion of pruritus-participant-level Standard Deviation 46.870	35.60 proportion of pruritus-participant-level Standard Deviation 42.748	69.18 proportion of pruritus-participant-level Standard Deviation 42.923
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 58-60	59.54 proportion of pruritus-participant-level Standard Deviation 45.249	46.44 proportion of pruritus-participant-level Standard Deviation 44.871	70.83 proportion of pruritus-participant-level Standard Deviation 40.675
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 68-70	62.42 proportion of pruritus-participant-level Standard Deviation 42.359	63.21 proportion of pruritus-participant-level Standard Deviation 43.450	64.35 proportion of pruritus-participant-level Standard Deviation 44.147
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 71-72	60.18 proportion of pruritus-participant-level Standard Deviation 41.743	60.74 proportion of pruritus-participant-level Standard Deviation 43.254	71.45 proportion of pruritus-participant-level Standard Deviation 41.406
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (AM Score) Weeks 73-76	33.22 proportion of pruritus-participant-level Standard Deviation 52.059	62.66 proportion of pruritus-participant-level Standard Deviation 29.530	69.93 proportion of pruritus-participant-level Standard Deviation 36.023

SECONDARY outcome

Timeframe: 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

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=37 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=53 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 9-12	57.77 proportion of pruritus-participant-level Standard Deviation 42.435	31.73 proportion of pruritus-participant-level Standard Deviation 38.223	72.42 proportion of pruritus-participant-level Standard Deviation 37.687
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 1-4	49.01 proportion of pruritus-participant-level Standard Deviation 35.687	24.13 proportion of pruritus-participant-level Standard Deviation 30.344	62.08 proportion of pruritus-participant-level Standard Deviation 34.404
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 5-8	60.03 proportion of pruritus-participant-level Standard Deviation 39.300	30.45 proportion of pruritus-participant-level Standard Deviation 35.987	73.11 proportion of pruritus-participant-level Standard Deviation 36.284
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 13-16	61.36 proportion of pruritus-participant-level Standard Deviation 41.530	33.08 proportion of pruritus-participant-level Standard Deviation 39.999	74.13 proportion of pruritus-participant-level Standard Deviation 38.607
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 17-20	56.49 proportion of pruritus-participant-level Standard Deviation 41.590	36.22 proportion of pruritus-participant-level Standard Deviation 41.689	76.12 proportion of pruritus-participant-level Standard Deviation 36.907
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 21-24	55.78 proportion of pruritus-participant-level Standard Deviation 43.495	36.28 proportion of pruritus-participant-level Standard Deviation 41.318	77.23 proportion of pruritus-participant-level Standard Deviation 37.626
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 34-36	58.75 proportion of pruritus-participant-level Standard Deviation 39.774	30.28 proportion of pruritus-participant-level Standard Deviation 39.297	75.11 proportion of pruritus-participant-level Standard Deviation 36.650
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 44-46	67.01 proportion of pruritus-participant-level Standard Deviation 39.601	38.02 proportion of pruritus-participant-level Standard Deviation 43.252	81.00 proportion of pruritus-participant-level Standard Deviation 30.974
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 47-48	71.08 proportion of pruritus-participant-level Standard Deviation 41.878	34.98 proportion of pruritus-participant-level Standard Deviation 43.148	74.62 proportion of pruritus-participant-level Standard Deviation 38.856
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 58-60	72.28 proportion of pruritus-participant-level Standard Deviation 38.149	43.53 proportion of pruritus-participant-level Standard Deviation 43.694	73.17 proportion of pruritus-participant-level Standard Deviation 38.473
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 68-70	62.63 proportion of pruritus-participant-level Standard Deviation 40.626	55.65 proportion of pruritus-participant-level Standard Deviation 42.883	74.85 proportion of pruritus-participant-level Standard Deviation 38.702
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 71-72	55.12 proportion of pruritus-participant-level Standard Deviation 42.336	53.97 proportion of pruritus-participant-level Standard Deviation 45.611	75.38 proportion of pruritus-participant-level Standard Deviation 39.038
Proportion of Positive Pruritus Assessments at the Participant Level Using the Albireo ObsRo Instrument (PM Score) Weeks 73-76	49.36 proportion of pruritus-participant-level Standard Deviation 36.671	63.35 proportion of pruritus-participant-level Standard Deviation 31.538	68.11 proportion of pruritus-participant-level Standard Deviation 32.377

SECONDARY outcome

Timeframe: 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

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

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 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction at specified Week against the thresholds value of 1.00 based on bi-weekly scores at specified Week obtained from blinded psychometric analysis across all anchors support a threshold of 1.0 point for AM, PM and AM and PM scratching 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=36 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=53 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 59-60	36.4 percentage of participants Interval 10.93 to 69.21	30.0 percentage of participants Interval 14.73 to 49.4	60.0 percentage of participants Interval 40.6 to 77.34
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 71-72	41.7 percentage of participants Interval 15.17 to 72.33	34.6 percentage of participants Interval 17.21 to 55.67	61.3 percentage of participants Interval 42.19 to 78.15
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 1-2	15.8 percentage of participants Interval 3.38 to 39.58	2.8 percentage of participants Interval 0.07 to 14.53	28.3 percentage of participants Interval 16.79 to 42.35
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 7-8	36.8 percentage of participants Interval 16.29 to 61.64	13.9 percentage of participants Interval 4.67 to 29.5	54.9 percentage of participants Interval 40.34 to 68.87
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 3-4	36.8 percentage of participants Interval 16.29 to 61.64	2.8 percentage of participants Interval 0.07 to 14.53	52.8 percentage of participants Interval 38.64 to 66.7
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 5-6	36.8 percentage of participants Interval 16.29 to 61.64	5.6 percentage of participants Interval 0.68 to 18.66	55.8 percentage of participants Interval 41.33 to 69.53
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 9-10	31.6 percentage of participants Interval 12.58 to 56.55	8.3 percentage of participants Interval 1.75 to 22.47	58.0 percentage of participants Interval 43.21 to 71.81
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 11-12	33.3 percentage of participants Interval 13.34 to 59.01	13.9 percentage of participants Interval 4.67 to 29.5	56.0 percentage of participants Interval 41.25 to 70.01
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 13-14	50.0 percentage of participants Interval 26.02 to 73.98	11.1 percentage of participants Interval 3.11 to 26.06	58.0 percentage of participants Interval 43.21 to 71.81
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 15-16	50.0 percentage of participants Interval 26.02 to 73.98	13.9 percentage of participants Interval 4.67 to 29.5	57.1 percentage of participants Interval 42.21 to 71.18
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 17-18	44.4 percentage of participants Interval 21.53 to 69.24	16.7 percentage of participants Interval 6.37 to 32.81	55.3 percentage of participants Interval 40.12 to 69.83
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 19-20	50.0 percentage of participants Interval 24.65 to 75.35	22.2 percentage of participants Interval 10.12 to 39.15	56.3 percentage of participants Interval 41.18 to 70.52
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 21-22	41.2 percentage of participants Interval 18.44 to 67.08	16.7 percentage of participants Interval 6.37 to 32.81	57.8 percentage of participants Interval 42.15 to 72.34
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 23-24	41.2 percentage of participants Interval 18.44 to 67.08	19.4 percentage of participants Interval 8.19 to 36.02	56.5 percentage of participants Interval 41.11 to 71.07
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 35-36	33.3 percentage of participants Interval 11.82 to 61.62	18.5 percentage of participants Interval 6.3 to 38.08	56.4 percentage of participants Interval 39.62 to 72.19
Percentage of Responders for Pruritus Assessments Bi-Weekly (AM and PM) Weeks 47-48	57.1 percentage of participants Interval 28.86 to 82.34	25.0 percentage of participants Interval 10.69 to 44.87	64.1 percentage of participants Interval 47.18 to 78.8

SECONDARY outcome

Timeframe: Weeks 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 34-36, 45-48, 58-60, and 68-72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

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 estimated from the blinded psychometric analysis. The averaged pruritus score was used to calculate the percentage of participants achieving meaningful reduction at specified Week against the thresholds value of 1.00 based on monthly scores at specified Week obtained from blinded psychometric analysis across all anchors support a threshold of 1.0 point for AM, PM and AM and PM scratching 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=36 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=53 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 1-4	21.1 percentage of participants Interval 6.05 to 45.57	2.8 percentage of participants Interval 0.07 to 14.53	43.4 percentage of participants Interval 29.84 to 57.72
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 5-8	36.8 percentage of participants Interval 16.29 to 61.64	8.3 percentage of participants Interval 1.75 to 22.47	54.9 percentage of participants Interval 40.34 to 68.87
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 9-12	36.8 percentage of participants Interval 16.29 to 61.64	11.1 percentage of participants Interval 3.11 to 26.06	56.0 percentage of participants Interval 41.25 to 70.01
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 13-16	50.0 percentage of participants Interval 26.02 to 73.98	13.9 percentage of participants Interval 4.67 to 29.5	60.0 percentage of participants Interval 45.18 to 73.59
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 17-20	38.9 percentage of participants Interval 17.3 to 64.25	16.7 percentage of participants Interval 6.37 to 32.81	56.3 percentage of participants Interval 41.18 to 70.52
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 21-24	35.3 percentage of participants Interval 14.21 to 61.67	16.7 percentage of participants Interval 6.37 to 32.81	53.3 percentage of participants Interval 37.87 to 68.34
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 34-36	43.8 percentage of participants Interval 19.75 to 70.12	23.3 percentage of participants Interval 9.93 to 42.28	58.1 percentage of participants Interval 42.13 to 72.99
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 45-48	53.3 percentage of participants Interval 26.59 to 78.73	24.1 percentage of participants Interval 10.3 to 43.54	64.1 percentage of participants Interval 47.18 to 78.8
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 58-60	46.2 percentage of participants Interval 19.22 to 74.87	29.0 percentage of participants Interval 14.22 to 48.04	57.1 percentage of participants Interval 39.35 to 73.68
Percentage of Responders for Pruritus Assessments Monthly (AM and PM) Weeks 68-72	53.8 percentage of participants Interval 25.13 to 80.78	37.5 percentage of participants Interval 18.8 to 59.41	64.5 percentage of participants Interval 45.37 to 80.77

SECONDARY outcome

Timeframe: Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with non-missing value when \>50% were included.

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. 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=12 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=26 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=31 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Percentage of Participants Achieving a Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO (AM and PM)	58.3 percentage of participants Interval 27.67 to 84.83	34.6 percentage of participants Interval 17.21 to 55.67	83.9 percentage of participants Interval 66.27 to 94.55

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, and 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment.

Participants who underwent biliary diversion surgery and or liver transplantation data has been reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=37 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=60 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation Weeks 0-72: Biliary Diversion Surgery	1 Participants	0 Participants	1 Participants
Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation Weeks 0-72: Liver Transplantation	2 Participants	0 Participants	5 Participants
Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation Weeks 0-24: Biliary Diversion Surgery	0 Participants	0 Participants	0 Participants
Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation Weeks 0-24: Liver Transplantation	1 Participants	0 Participants	0 Participants
Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation Weeks 0-48: Liver Transplantation	2 Participants	0 Participants	2 Participants
Number of Participants Who Underwent Biliary Diversion Surgery and Liver Transplantation Weeks 0-48: Biliary Diversion Surgery	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 70 and 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Growth factors like height was measured by the standardized assessments outlined in the US food and drug administration (FDA) guidance document. 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. Participants whose accurate age was not available, Z-score was not calculated. Baseline is the last available assessment prior to first dose of study treatment. A Z-score indicates how many standard deviation's (SD) a participant's measurement (like height), 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=15 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=28 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=46 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline in Height Z-Scores Week 24	0.181 Z-score Interval -0.28 to 1.53	0.341 Z-score Interval -1.04 to 2.26	0.089 Z-score Interval -1.34 to 1.97
Change From Baseline in Height Z-Scores Week 48	0.485 Z-score Interval 0.02 to 1.42	0.662 Z-score Interval -0.75 to 2.08	0.095 Z-score Interval -1.46 to 2.03
Change From Baseline in Height Z-Scores Average of Weeks 70-72	0.556 Z-score Interval -0.01 to 1.57	0.543 Z-score Interval -0.83 to 2.12	0.224 Z-score Interval -1.42 to 2.62

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 70 and 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Growth factors like weight was measured by the standardized assessments outlined in the US FDA guidance document. 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. Participants whose accurate age was not available, Z-score was not calculated. Baseline is the last available assessment prior to the first dose of study treatment. The Z-score indicates how many SDs a participant's measurement (like weight), 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=15 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=29 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=48 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline in Weight Z-Scores Week 24	0.155 Z-score Interval -0.49 to 1.4	0.383 Z-score Interval -0.75 to 1.57	0.169 Z-score Interval -0.68 to 1.74
Change From Baseline in Weight Z-Scores Week 48	0.544 Z-score Interval -1.15 to 1.43	0.494 Z-score Interval -1.04 to 2.14	0.246 Z-score Interval -0.54 to 1.29
Change From Baseline in Weight Z-Scores Average of Weeks 70-72	0.098 Z-score Interval -1.13 to 2.17	0.389 Z-score Interval -1.21 to 2.11	0.400 Z-score Interval -0.86 to 2.27

SECONDARY outcome

Timeframe: Baseline and Weeks 24, 48, 70 and 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Growth factors like BMI was measured by the standardized assessments outlined in the US FDA guidance document. BMI was calculated by weight (kg) / height (m)\^2. 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. Participants whose accurate age was not available, Z-score was not calculated. Baseline is the last available assessment prior to the first dose of study treatment. The Z-score indicates how many SDs a participant's measurement (like BMI), 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=15 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=28 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=46 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline in Body Mass Index (BMI) Z-Scores Week 24	-0.106 Z-score Interval -0.66 to 1.86	0.150 Z-score Interval -2.0 to 2.21	0.202 Z-score Interval -1.6 to 2.08
Change From Baseline in Body Mass Index (BMI) Z-Scores Week 48	0.028 Z-score Interval -0.88 to 1.23	-0.135 Z-score Interval -2.44 to 2.59	0.129 Z-score Interval -1.34 to 2.45
Change From Baseline in Body Mass Index (BMI) Z-Scores Average of Weeks 70-72	-0.059 Z-score Interval -1.24 to 3.12	-0.007 Z-score Interval -1.64 to 2.25	0.182 Z-score Interval -0.99 to 2.68

SECONDARY outcome

Timeframe: Weeks 24, 48, and 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at specified timepoints are reported.

Data for the number of participants with use of UDCA and rifampicin are reported.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=19 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=37 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=60 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 48: Use of UDCA or Rifampicin	18 Participants	33 Participants	46 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 48: Use of UDCA and Rifampicin	14 Participants	14 Participants	24 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 72: Use of UDCA	14 Participants	24 Participants	34 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 72: Use of Rifampicin	14 Participants	15 Participants	26 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 72: Use of UDCA or Rifampicin	16 Participants	29 Participants	41 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 72: Use of UDCA and Rifampicin	12 Participants	10 Participants	19 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 48: Use of Rifampicin	16 Participants	20 Participants	31 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 24: Use of UDCA	17 Participants	29 Participants	43 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 24: Use of Rifampicin	17 Participants	19 Participants	37 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 24: Use of UDCA or Rifampicin	19 Participants	33 Participants	50 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 24: Use of UDCA and Rifampicin	15 Participants	15 Participants	30 Participants
Number of Participants With Use of Ursodeoxycholic Acid (UDCA) and/or Rifampicin at Weeks 24, 48, and 72 Week 48: Use of UDCA	16 Participants	27 Participants	39 Participants

SECONDARY outcome

Timeframe: Baseline and Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.

The PELD score was calculated for children under 12 years of age, ranged across negative to positive values. The calculation of the 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 \[\<-2 standard deviation\]). The laboratory values \<1.0 were set to 1.0 for the calculation of the PELD score. Lower scores represent less severe hepatic disease. Baseline is the last available assessment prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=11 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=20 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=23 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline to Week 72 in Pediatric End-Stage Liver Disease (PELD) Score	-0.397 score on a scale Standard Deviation 3.6168	1.361 score on a scale Standard Deviation 2.5083	-0.303 score on a scale Standard Deviation 9.4631

SECONDARY outcome

Timeframe: Baseline and Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants 12 years of age or older are included in this analysis and reported. For Cohort 1: Placebo/Odevixibat change from baseline data was not collected as participant was under 12 years old, that aligns with MELD score calculation.

The MELD score was calculated for children 12 years of age or older ranges from 6 to 40. The calculation of the 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 for children 12 years of age or older ranges from 6 to 40 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 is the last available assessment prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=1 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=3 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=17 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline to Week 72 in Model for End-stage Liver Disease (MELD) Score for Children 12 Years of Age or Older Baseline	6.869 score on a scale Standard Deviation NA NA indicates standard deviation not calculated for single participant.	9.795 score on a scale Standard Deviation 2.4694	11.574 score on a scale Standard Deviation 4.0801
Change From Baseline to Week 72 in Model for End-stage Liver Disease (MELD) Score for Children 12 Years of Age or Older Change from Baseline	—	1.286 score on a scale Standard Deviation NA NA indicates standard deviation not calculated for single participant.	-2.221 score on a scale Standard Deviation 5.7744

SECONDARY outcome

Timeframe: Baseline and Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.

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 is the last available assessment prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=13 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=21 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=22 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline to Week 72 in Aspartate Aminotransferase (AST) to Platelet Ratio Index (APRI) Score	0.044 score on a scale Standard Deviation 0.3435	0.071 score on a scale Standard Deviation 0.3951	0.411 score on a scale Standard Deviation 0.9690

SECONDARY outcome

Timeframe: Baseline and Week 72

Population: The FAS consisted of all participants who had received at least 1 dose of the study treatment. Only participants with data collected at Baseline and Week 72 are reported.

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 \> 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 is the last available assessment prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Placebo/Odevixibat n=13 Participants Participants who previously received placebo in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 1: Odevixibat/Odevixibat n=21 Participants Participants who previously received odevixibat capsule orally at a dose of 40 or 120 mcg/kg/day in study A4250-005 (NCT03566238) for 24 weeks received odevixibat capsule orally at a dose of 120 mcg/kg/day for 72 weeks, unless they required down-titration to the 40 mcg/kg/day due to tolerability issues.	Cohort 2: Odevixibat n=21 Participants Participants any age with any type of PFIC who either did not meet eligibility criteria for study A4250-005 (NCT03566238) or were eligible for enrolment in A4250-005 (NCT03566238) after recruitment was complete received odevixibat at a dose of 120 μg/kg/day or following protocol amendment 6.0, initiated at a dose of 40 mcg/kg/day with the possibility to dose escalate to 120 mcg/kg/day after 12 weeks if there was no improvement in pruritus based on investigator judgement, up to 72 weeks.
Change From Baseline to Week 72 in Fibrosis-4 (Fib-4) Score	0.050 score on a scale Standard Deviation 0.1187	0.106 score on a scale Standard Deviation 0.2696	0.113 score on a scale Standard Deviation 0.2820

Adverse Events

Cohort 1: Placebo/Odevixibat

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Cohort 1: Odevixibat/Odevixibat

Serious events: 7 serious events

Other events: 35 other events

Deaths: 0 deaths

Cohort 2: Odevixibat

Serious events: 23 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Albireo, An Ipsen Company

Phone: see email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER