PFIC1, PFIC2
Conditions
Keywords
Pediatric, Cholestasis
Brief summary
Double blind, randomized, placebo controlled, Phase 3 study to investigate the efficacy and safety of low doses and high doses of A4250 compared to placebo in children with progressive familial intrahepatic cholestasis (PFIC) types 1 and 2.
Detailed description
Up to 50 sites in the following countries will take part in this study: Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Sweden, Turkey, United Kingdom, United States, and Saudi Arabia
Interventions
A4250 is a small molecule and selective inhibitor of ileal bile acid transporter (IBAT).
DRUGPlacebo
Placebo identical in appearance to active drug (A4250).
Sponsors
Albireo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-Blind, Randomized, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * A male or female participant with a clinical diagnosis of PFIC Type 1 or 2 and with a body weight above 5 kg * Participant must have clinical genetic confirmation of PFIC-1 or PFIC-2 * Participant must have elevated serum bile acid (s-BA) concentration * Participant must have history of significant pruritus and a caregiver reported observed scratching in the eDiary * Participant and/or legal guardian must sign informed consent (and assent) as appropriate. * Participants will be expected to have a consistent caregiver(s) for the duration of the study * Caregivers and age-appropriate participants (≥8 years of age) must be willing and able to use an eDiary device as required by the study Key
Exclusion criteria
* Participant with pathologic variations of the ABCB11 gene that predict complete absence of the bile salt export pump (BSEP) protein * Participant with past medical history or ongoing presence of other types of liver disease including, but not limited to, the following: 1. Biliary atresia of any kind 2. Benign recurrent intrahepatic cholestasis, indicated by any history of normal s BAs 3. Suspected or proven liver cancer or metastasis to the liver on imaging studies 4. Histopathology on liver biopsy that is suggestive of alternate non-PFIC related etiology of cholestasis * Participant with past medical history or ongoing chronic diarrhea * Any participant with suspected or confirmed cancers except for basal cell carcinoma * Participant with a past medical history of chronic kidney disease with an impaired renal function and a glomerular filtration rate \<70 mL/min/1.73 m\^2 * Participant with surgical history of disruption of the enterohepatic circulation (biliary diversion surgery) within 6 months prior to start of Screening Period * Participant has had a liver transplant or a liver transplant is planned within 6 months of randomization * Decompensated liver disease * Participant suffers from uncontrolled, recalcitrant pruritic condition other than PFIC * Participant who has been previously treated with an IBAT inhibitor whose pruritus has not responded to treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment | From Baseline (Day 1) up to Week 24 | Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in fasting s-BA from baseline to the end of treatment or reached \<=70 mcmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Percentages are rounded to hundredth decimal. |
| Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period | From Baseline (Day 1) up to Week 24 | A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline. The percentage 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 multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Growth Parameters at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | The change in the growth parameters was assessed using linear growth deficit \[height (centimeter), weight (kilogram) and body mass index (BMI) (kg/meter square)\] 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 website for participants with age \<2 years old. Participants whose accurate age was not available, Z-score was not calculated. A Z-score indicated how many standard deviation's (SD) a participant's measurement (like height, weight and 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 average a measurement was. Baseline was the last available assessment before the first dose of study treatment. |
| Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | Weeks 12 and 24 | The responder for pruritus scores was defined as a participant who achieved at least a 1-point reduction in the ObsRO pruritus score. Percentages are rounded to hundredth decimal. |
| Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 | The sleep disturbance were recorded twice daily via the electronic diary (eDiary). Participants and/or caregivers completed the eDiary every day in the morning and in the evening. The morning diary was completed shortly after the participant woke up and was used to record nighttime itching and scratching severity, aspects of sleep disturbance, and tiredness upon waking (AM scores). The evening/bedtime diary was completed just before the participant went to bed and recorded participant's itching and scratching severity, and tiredness during the day (PM scores). Both morning and bedtime diaries included Albireo ObsRO and PRO items. Baseline was the average of 14-day scores before the first dose of study treatment. |
| Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24 | The ObsRO and electronic diary (eDiary) PRO scale called PRUCISION was used to assess pruritus and sleep outcomes. Participants and/or caregivers completed the eDiary every day in the morning (AM scores) and in the evening (PM scores). Specifically, for difficulty falling or staying asleep, the following 2 respective questions were asked in the Morning Daily eDiary: 1) How hard was it to fall asleep last night because of your itching. and 2) How hard was it to stay asleep last night because of your itching. The PRO was a 5-point scale, and scores ranged from 0 (no itching) to 28 (the worst itching), where higher scores indicated a greater amount of itching, sleep disturbance, and tiredness. No subscales were used. Change in sleep parameters measured with the Albireo PRO and ObsRO instruments by each 4-week interval over the 24-week treatment period was assessed. Baseline was the average of 14-day scores before the first dose of study treatment. |
| Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | Blood samples for analysis of s-BA were drawn at all visits. Participants were to fast (water intake only was permissible) for at least 4 hours prior to the collection of samples. Exceptions could be made for infants \<12 months of age if they were unable to fast for the full 4 hours. Baseline was the average of the last 2 non-missing values of fasting s-BA concentration prior to the first dose of study treatment. |
| Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | From Baseline (Day 1) up to Week 24 | A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based on the Albireo PRO instrument, only participants \>=8 years of age completed the Albireo PRO instrument. The percentage 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 multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. |
| Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | From Baseline (Day 1) up to Week 24 | The number of participants underwent biliary diversion surgery and liver transplantation was determined. |
| Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | From Baseline (Day 1) up to Week 24 | A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based on the Albireo ObsRO and PRO instruments. The percentage 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 multiplied by 100. |
| Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | From Baseline (Day 1) up to Week 24 | A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based 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 only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively. |
| Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | Blood samples were collected to determine the ALT concentration. Baseline was the last available assessment before the first dose of study treatment. |
Countries
Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Saudi Arabia, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This Phase 3, double-blind, placebo-controlled study was conducted in children with progressive familial intrahepatic cholestasis (PFIC) at 33 study centers in 12 countries between 16 May 2018 and 28 July 2020.
Pre-assignment details
The study included up to an 8-week screening period, a 24-week treatment period, and a 4-week follow-up period. A total of 62 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Capsules for oral administration (to match active) once daily for 24 weeks.
Placebo: Placebo identical in appearance to active drug (A4250). | 20 |
| A4250 Low Dose Capsules for oral administration (40 mcg/kg) once daily for 24 weeks.
A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | 23 |
| A4250 High Dose Capsules for oral administration (120 mcg/kg) once daily for 24 weeks.
A4250 (odevixibat): A4250 is a small molecule and selective inhibitor of IBAT. | 19 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 4 | 2 |
| Overall Study | Other | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | A4250 High Dose | A4250 Low Dose |
|---|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 62 Participants | 19 Participants | 23 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 3.75 years STANDARD_DEVIATION 3.853 | 4.25 years STANDARD_DEVIATION 3.883 | 5.24 years STANDARD_DEVIATION 4.188 | 3.86 years STANDARD_DEVIATION 3.66 |
| Age, Customized Age Category 1 13 to 18 years | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Age, Customized Age Category 1 6 months to 5 years | 16 Participants | 47 Participants | 14 Participants | 17 Participants |
| Age, Customized Age Category 1 6 to 12 years | 3 Participants | 12 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 19 Participants | 61 Participants | 19 Participants | 23 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 17 Participants | 52 Participants | 17 Participants | 18 Participants |
| Region of Enrollment Australia | 1 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Canada | 1 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment France | 1 participants | 5 participants | 1 participants | 3 participants |
| Region of Enrollment Germany | 2 participants | 9 participants | 4 participants | 3 participants |
| Region of Enrollment Israel | 1 participants | 2 participants | 1 participants | 0 participants |
| Region of Enrollment Italy | 1 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment Netherlands | 1 participants | 3 participants | 2 participants | 0 participants |
| Region of Enrollment Poland | 2 participants | 3 participants | 1 participants | 0 participants |
| Region of Enrollment Saudi Arabia | 1 participants | 3 participants | 2 participants | 0 participants |
| Region of Enrollment Turkey | 1 participants | 11 participants | 3 participants | 7 participants |
| Region of Enrollment United Kingdom | 5 participants | 13 participants | 2 participants | 6 participants |
| Region of Enrollment United States | 3 participants | 8 participants | 3 participants | 2 participants |
| Sex: Female, Male Female | 8 Participants | 31 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 31 Participants | 8 Participants | 11 Participants |
| Type of PFIC Type 1 | 5 Participants | 17 Participants | 5 Participants | 7 Participants |
| Type of PFIC Type 2 | 15 Participants | 45 Participants | 14 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 23 | 0 / 19 |
| other Total, other adverse events | 17 / 20 | 19 / 23 | 16 / 19 |
| serious Total, serious adverse events | 5 / 20 | 0 / 23 | 3 / 19 |
Outcome results
Primary
Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment
Fasting s-BA baseline was calculated as the average of the last 2 values prior to the first dose. The end value was the average of the values at Weeks 22 and 24 after the start of double-blind treatment. Participants who had at least 70% reduction in fasting s-BA from baseline to the end of treatment or reached \<=70 mcmol/L after 24 weeks of treatment were considered as responder. Participants with missing average at the end of treatment were classified as non-responder. Percentages are rounded to hundredth decimal.
Time frame: From Baseline (Day 1) up to Week 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment | 0 percentage of participants |
| A4250 Low Dose | Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment | 43.5 percentage of participants |
| A4250 High Dose | Percentage of Participants With at Least a 70% Reduction in Fasting Serum Bile Acid (s-BA) Concentration From Baseline to the End of Treatment or Reaching a Level <=70 Micromoles Per Liter (Mcmol/L) After 24 Weeks of Treatment | 21.1 percentage of participants |
Comparison: Analysis was based on the Cochran Mantel Haenszel test adjusting PFIC type. A pooled analysis for the closed testing procedure was applied to control multiplicity. The 1-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses.~1-sided adjusted p-value was reported.p-value: 0.001595% CI: [0.2195, 0.6551]Cochran-Mantel-Haenszel
Comparison: Analysis was based on the Cochran Mantel Haenszel test adjusting PFIC type. A pooled analysis for the closed testing procedure was applied to control multiplicity. The 1-sided adjusted p-value for an individual dose was calculated as the maximum value of the unadjusted p-value for the pooled analysis and the unadjusted p-value for the individual doses.~1-sided adjusted p-value was reported.p-value: 0.017495% CI: [0.021, 0.4557]Cochran-Mantel-Haenszel
Primary
Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period
A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline. The percentage 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 multiplied by 100.
Time frame: From Baseline (Day 1) up to Week 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period | 28.74 percentage of assessments | Standard Error 5.209 |
| A4250 Low Dose | Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period | 58.31 percentage of assessments | Standard Error 6.205 |
| A4250 High Dose | Percentage of Positive Pruritus Assessments at the Participant Level Based on the Albireo Observer-Reported Outcome (ObsRO) Instrument Over the 24-Week Treatment Period | 47.69 percentage of assessments | Standard Error 8.11 |
Comparison: Analysis of the Proportion of Positive Pruritus Assessments at Participant Level over the 24-Week Treatment Period - Albireo ObsRO Instrument (AM and PM Scores).p-value: 0.001995% CI: [9.83, 46.64]ANCOVA
Comparison: Analysis of the Proportion of Positive Pruritus Assessments at Participant Level over the 24-Week Treatment Period - Albireo ObsRO Instrument (AM and PM Scores).p-value: 0.016395% CI: [1.87, 41.54]ANCOVA
Secondary
Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24
Blood samples for analysis of s-BA were drawn at all visits. Participants were to fast (water intake only was permissible) for at least 4 hours prior to the collection of samples. Exceptions could be made for infants \<12 months of age if they were unable to fast for the full 4 hours. Baseline was the average of the last 2 non-missing values of fasting s-BA concentration prior to the first dose of study treatment.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at Baseline and Weeks 12 and 24 are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Week 24 | 18.64 mcmol/L | Standard Error 31.559 |
| Placebo | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Week 12 | 7.44 mcmol/L | Standard Error 24.588 |
| A4250 Low Dose | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Week 12 | -113.70 mcmol/L | Standard Error 38.011 |
| A4250 Low Dose | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Week 24 | -145.03 mcmol/L | Standard Error 41.951 |
| A4250 High Dose | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Week 12 | -106.44 mcmol/L | Standard Error 41.201 |
| A4250 High Dose | Change From Baseline in Fasting Serum Bile Acid at Weeks 12 and 24 | Week 24 | -72.90 mcmol/L | Standard Error 52.617 |
Secondary
Change From Baseline in Growth Parameters at Weeks 12 and 24
The change in the growth parameters was assessed using linear growth deficit \[height (centimeter), weight (kilogram) and body mass index (BMI) (kg/meter square)\] 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 website for participants with age \<2 years old. Participants whose accurate age was not available, Z-score was not calculated. A Z-score indicated how many standard deviation's (SD) a participant's measurement (like height, weight and 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 average a measurement was. Baseline was the last available assessment before the first dose of study treatment.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at Baseline and Weeks 12 and 24 are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Height deficit: Week 12 | -0.03 z-score | Standard Error 0.127 |
| Placebo | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Height deficit: Week 24 | -0.16 z-score | Standard Error 0.104 |
| Placebo | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Weight deficit: Week 12 | 0.13 z-score | Standard Error 0.066 |
| Placebo | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Weight deficit: Week 24 | 0.10 z-score | Standard Error 0.102 |
| Placebo | Change From Baseline in Growth Parameters at Weeks 12 and 24 | BMI deficit: Week 12 | 0.18 z-score | Standard Error 0.148 |
| Placebo | Change From Baseline in Growth Parameters at Weeks 12 and 24 | BMI deficit: Week 24 | 0.26 z-score | Standard Error 0.156 |
| A4250 Low Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | BMI deficit: Week 24 | 0.36 z-score | Standard Error 0.113 |
| A4250 Low Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Height deficit: Week 12 | 0.01 z-score | Standard Error 0.108 |
| A4250 Low Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Weight deficit: Week 24 | 0.29 z-score | Standard Error 0.106 |
| A4250 Low Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | BMI deficit: Week 12 | 0.23 z-score | Standard Error 0.114 |
| A4250 Low Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Height deficit: Week 24 | 0.05 z-score | Standard Error 0.105 |
| A4250 Low Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Weight deficit: Week 12 | 0.20 z-score | Standard Error 0.078 |
| A4250 High Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Height deficit: Week 24 | 0.00 z-score | Standard Error 0.163 |
| A4250 High Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Weight deficit: Week 12 | 0.00 z-score | Standard Error 0.1 |
| A4250 High Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | BMI deficit: Week 24 | 0.20 z-score | Standard Error 0.203 |
| A4250 High Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Weight deficit: Week 24 | 0.15 z-score | Standard Error 0.124 |
| A4250 High Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | Height deficit: Week 12 | -0.06 z-score | Standard Error 0.1 |
| A4250 High Dose | Change From Baseline in Growth Parameters at Weeks 12 and 24 | BMI deficit: Week 12 | 0.08 z-score | Standard Error 0.147 |
Secondary
Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24
Blood samples were collected to determine the ALT concentration. Baseline was the last available assessment before the first dose of study treatment.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at Baseline and Weeks 12 and 24 are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Week 12 | 1.7 units/L | Standard Error 10.5 |
| Placebo | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Week 24 | 3.7 units/L | Standard Error 4.95 |
| A4250 Low Dose | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Week 12 | -25.9 units/L | Standard Error 23.36 |
| A4250 Low Dose | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Week 24 | -27.9 units/L | Standard Error 17.97 |
| A4250 High Dose | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Week 12 | -13.8 units/L | Standard Error 19.42 |
| A4250 High Dose | Change From Baseline in Serum Alanine Aminotransferase (ALT) Concentration at Weeks 12 and 24 | Week 24 | -25.3 units/L | Standard Error 22.47 |
Secondary
Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period
The sleep disturbance were recorded twice daily via the electronic diary (eDiary). Participants and/or caregivers completed the eDiary every day in the morning and in the evening. The morning diary was completed shortly after the participant woke up and was used to record nighttime itching and scratching severity, aspects of sleep disturbance, and tiredness upon waking (AM scores). The evening/bedtime diary was completed just before the participant went to bed and recorded participant's itching and scratching severity, and tiredness during the day (PM scores). Both morning and bedtime diaries included Albireo ObsRO and PRO items. Baseline was the average of 14-day scores before the first dose of study treatment.
Time frame: Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 17 to 20 | -6.27 percentage of days | Standard Error 3.862 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 9 to 12 | 2.40 percentage of days | Standard Error 4.271 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 9 to 12 | -5.74 percentage of days | Standard Error 3.585 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 21 to 24 | -3.19 percentage of days | Standard Error 2.89 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 17 to 20 | -22.02 percentage of days | Standard Error 7.999 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 5 to 8 | -5.93 percentage of days | Standard Error 3.649 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 1 to 4 | -1.15 percentage of days | Standard Error 1.338 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 17 to 20 | 3.53 percentage of days | Standard Error 5.384 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 1 to 4 | -4.49 percentage of days | Standard Error 1.961 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 5 to 8 | -3.76 percentage of days | Standard Error 2.773 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 5 to 8 | 1.44 percentage of days | Standard Error 4.292 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 21 to 24 | -7.64 percentage of days | Standard Error 6.182 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 9 to 12 | -5.00 percentage of days | Standard Error 2.819 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 21 to 24 | -23.72 percentage of days | Standard Error 8.563 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 17 to 20 | -4.73 percentage of days | Standard Error 3.742 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 13 to 16 | -2.12 percentage of days | Standard Error 3.006 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 9 to 12 | -13.49 percentage of days | Standard Error 6.32 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 1 to 4 | -1.78 percentage of days | Standard Error 1.921 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 1 to 4 | -0.91 percentage of days | Standard Error 1.596 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 5 to 8 | -12.10 percentage of days | Standard Error 6.353 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 21 to 24 | -5.45 percentage of days | Standard Error 4.844 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 5 to 8 | -2.35 percentage of days | Standard Error 2.397 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 13 to 16 | 0.16 percentage of days | Standard Error 4.647 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 1 to 4 | -15.79 percentage of days | Standard Error 4.7 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 9 to 12 | -0.90 percentage of days | Standard Error 1.152 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 13 to 16 | -15.75 percentage of days | Standard Error 6.264 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 17 to 20 | -2.59 percentage of days | Standard Error 3.688 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 13 to 16 | -0.86 percentage of days | Standard Error 1.392 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 21 to 24 | 5.50 percentage of days | Standard Error 5.307 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 13 to 16 | -4.96 percentage of days | Standard Error 3.481 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 17 to 20 | -42.20 percentage of days | Standard Error 10.247 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 1 to 4 | -14.42 percentage of days | Standard Error 5.854 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 5 to 8 | -26.22 percentage of days | Standard Error 7.427 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 9 to 12 | -29.22 percentage of days | Standard Error 7.593 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 13 to 16 | -33.38 percentage of days | Standard Error 8.219 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 17 to 20 | -32.14 percentage of days | Standard Error 8.531 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 21 to 24 | -30.82 percentage of days | Standard Error 8.184 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 1 to 4 | -14.73 percentage of days | Standard Error 5.683 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 5 to 8 | -25.03 percentage of days | Standard Error 7.527 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 9 to 12 | -31.03 percentage of days | Standard Error 8.061 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 13 to 16 | -46.10 percentage of days | Standard Error 9.677 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 17 to 20 | -45.65 percentage of days | Standard Error 9.524 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 21 to 24 | -51.75 percentage of days | Standard Error 9.857 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 1 to 4 | -12.92 percentage of days | Standard Error 5.911 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 5 to 8 | -17.89 percentage of days | Standard Error 7.562 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 9 to 12 | -29.79 percentage of days | Standard Error 8.57 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 13 to 16 | -42.79 percentage of days | Standard Error 10.364 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 17 to 20 | -44.96 percentage of days | Standard Error 10.485 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 21 to 24 | -51.48 percentage of days | Standard Error 10.323 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 1 to 4 | -15.30 percentage of days | Standard Error 6.396 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 5 to 8 | -19.73 percentage of days | Standard Error 7.061 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 9 to 12 | -26.12 percentage of days | Standard Error 9.543 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 13 to 16 | -40.55 percentage of days | Standard Error 10.501 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 21 to 24 | -49.35 percentage of days | Standard Error 10.466 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 1 to 4 | -0.61 percentage of days | Standard Error 1.913 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 5 to 8 | 0.18 percentage of days | Standard Error 3.018 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 9 to 12 | 1.31 percentage of days | Standard Error 3.656 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 13 to 16 | -1.61 percentage of days | Standard Error 2.556 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 17 to 20 | -1.99 percentage of days | Standard Error 2.141 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 21 to 24 | -0.03 percentage of days | Standard Error 2.251 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 17 to 20 | -40.51 percentage of days | Standard Error 12.566 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 9 to 12 | -16.89 percentage of days | Standard Error 9.258 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 9 to 12 | -36.00 percentage of days | Standard Error 10.361 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 13 to 16 | -37.76 percentage of days | Standard Error 12.013 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 1 to 4 | -12.97 percentage of days | Standard Error 6.036 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 13 to 16 | -37.52 percentage of days | Standard Error 11.083 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 9 to 12 | -36.72 percentage of days | Standard Error 11.154 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 5 to 8 | -31.49 percentage of days | Standard Error 10.209 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 17 to 20 | -35.14 percentage of days | Standard Error 11.563 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 1 to 4 | -20.37 percentage of days | Standard Error 6.39 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 13 to 16 | -4.58 percentage of days | Standard Error 4.681 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 21 to 24 | -33.14 percentage of days | Standard Error 11.801 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 21 to 24 | -15.52 percentage of days | Standard Error 10.465 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 5 to 8 | -13.99 percentage of days | Standard Error 7.77 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 1 to 4 | 0.98 percentage of days | Standard Error 2.32 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 17 to 20 | -18.02 percentage of days | Standard Error 9.967 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 21 to 24 | 2.04 percentage of days | Standard Error 8.413 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 13 to 16 | -40.23 percentage of days | Standard Error 11.611 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 9 to 12 | -41.21 percentage of days | Standard Error 10.796 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 5 to 8 | -2.43 percentage of days | Standard Error 3.036 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 17 to 20 | -40.13 percentage of days | Standard Error 12.324 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 5 to 8 | -35.97 percentage of days | Standard Error 9.795 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Seeing blood due to scratching: Weeks 13 to 16 | -18.16 percentage of days | Standard Error 9.403 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 21 to 24 | -34.87 percentage of days | Standard Error 13.369 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Soothing: Weeks 1 to 4 | -21.88 percentage of days | Standard Error 6.228 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 17 to 20 | -3.26 percentage of days | Standard Error 6.403 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 1 to 4 | -24.57 percentage of days | Standard Error 7.024 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Help falling asleep: Weeks 21 to 24 | -32.58 percentage of days | Standard Error 14.573 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Taking medications to induce sleep: Weeks 9 to 12 | -5.74 percentage of days | Standard Error 4.967 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Observer-reported Outcome Instrument Over the 24-Week Treatment Period | Sleeping with the caregiver: Weeks 5 to 8 | -35.58 percentage of days | Standard Error 10.053 |
Secondary
Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period
The ObsRO and electronic diary (eDiary) PRO scale called PRUCISION was used to assess pruritus and sleep outcomes. Participants and/or caregivers completed the eDiary every day in the morning (AM scores) and in the evening (PM scores). Specifically, for difficulty falling or staying asleep, the following 2 respective questions were asked in the Morning Daily eDiary: 1) How hard was it to fall asleep last night because of your itching. and 2) How hard was it to stay asleep last night because of your itching. The PRO was a 5-point scale, and scores ranged from 0 (no itching) to 28 (the worst itching), where higher scores indicated a greater amount of itching, sleep disturbance, and tiredness. No subscales were used. Change in sleep parameters measured with the Albireo PRO and ObsRO instruments by each 4-week interval over the 24-week treatment period was assessed. Baseline was the average of 14-day scores before the first dose of study treatment.
Time frame: Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 1 to 4 | -0.46 scores on a scale | Standard Error 0.143 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 5 to 8 | -0.34 scores on a scale | Standard Error 0.018 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 9 to 12 | -0.38 scores on a scale | Standard Error 0.339 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 13 to 16 | -0.16 scores on a scale | Standard Error 0.268 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 17 to 20 | -0.52 scores on a scale | Standard Error 0.228 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 21 to 24 | -0.25 scores on a scale | Standard Error 0.179 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 1 to 4 | -0.13 scores on a scale | Standard Error 0.411 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 5 to 8 | 0.09 scores on a scale | Standard Error 0.518 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 9 to 12 | 0.02 scores on a scale | Standard Error 0.661 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 13 to 16 | 0.13 scores on a scale | Standard Error 0.625 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 17 to 20 | -0.15 scores on a scale | Standard Error 0.147 |
| Placebo | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 21 to 24 | 0.25 scores on a scale | Standard Error 0.429 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 21 to 24 | -2.55 scores on a scale | Standard Error 0.448 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 1 to 4 | -0.72 scores on a scale | Standard Error 0.494 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 1 to 4 | -0.70 scores on a scale | Standard Error 0.548 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 9 to 12 | -2.51 scores on a scale | Standard Error 0.352 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 5 to 8 | -1.40 scores on a scale | Standard Error 1.009 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 21 to 24 | -2.22 scores on a scale | Standard Error 0.823 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 17 to 20 | -2.36 scores on a scale | Standard Error 0.637 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 9 to 12 | -2.31 scores on a scale | Standard Error 0.499 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 5 to 8 | -1.48 scores on a scale | Standard Error 0.932 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 17 to 20 | -2.12 scores on a scale | Standard Error 0.974 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 13 to 16 | -2.07 scores on a scale | Standard Error 0.863 |
| A4250 Low Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 13 to 16 | -2.46 scores on a scale | Standard Error 0.464 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 13 to 16 | -1.01 scores on a scale | Standard Error 0.665 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 17 to 20 | -1.02 scores on a scale | Standard Error 0.71 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 13 to 16 | -0.89 scores on a scale | Standard Error 0.626 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 21 to 24 | -0.82 scores on a scale | Standard Error 0.658 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 1 to 4 | -0.43 scores on a scale | Standard Error 0.44 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 5 to 8 | -0.50 scores on a scale | Standard Error 0.553 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 17 to 20 | -0.95 scores on a scale | Standard Error 0.644 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 1 to 4 | -0.59 scores on a scale | Standard Error 0.394 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 5 to 8 | -0.65 scores on a scale | Standard Error 0.571 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 9 to 12 | -0.77 scores on a scale | Standard Error 0.67 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty falling asleep: Weeks 9 to 12 | -0.95 scores on a scale | Standard Error 0.65 |
| A4250 High Dose | Change From Baseline in Sleep Parameters Based on the Albireo Patient-Reported Outcome (PRO) Instrument Over the 24-Week Treatment Period | Difficulty staying asleep: Weeks 21 to 24 | -0.78 scores on a scale | Standard Error 0.633 |
Secondary
Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period
A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based on the Albireo ObsRO and PRO instruments. The percentage 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 multiplied by 100.
Time frame: From Baseline (Day 1) up to Week 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected for specific instrument are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: AM and PM scores combined | 4 Participants |
| Placebo | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: AM score | 3 Participants |
| Placebo | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: PM score | 5 Participants |
| Placebo | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: AM and PM scores combined | 0 Participants |
| Placebo | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: AM score | 0 Participants |
| Placebo | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: PM score | 0 Participants |
| A4250 Low Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: PM score | 1 Participants |
| A4250 Low Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: AM and PM scores combined | 17 Participants |
| A4250 Low Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: AM and PM scores combined | 1 Participants |
| A4250 Low Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: AM score | 1 Participants |
| A4250 Low Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: AM score | 13 Participants |
| A4250 Low Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: PM score | 16 Participants |
| A4250 High Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: AM score | 10 Participants |
| A4250 High Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: PM score | 9 Participants |
| A4250 High Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: PM score | 3 Participants |
| A4250 High Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: AM and PM scores combined | 3 Participants |
| A4250 High Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo ObsRO Instrument: AM and PM scores combined | 9 Participants |
| A4250 High Dose | Number of Participants Achieved Positive Pruritus Assessment for >50% of the Time Based on the Albireo ObsRO and PRO Instruments Over the 24-Week Treatment Period | Albireo PRO Instrument: AM score | 3 Participants |
Secondary
Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation
The number of participants underwent biliary diversion surgery and liver transplantation was determined.
Time frame: From Baseline (Day 1) up to Week 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | Biliary diversion surgery | 0 Participants |
| Placebo | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | Liver transplantation | 0 Participants |
| A4250 Low Dose | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | Biliary diversion surgery | 0 Participants |
| A4250 Low Dose | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | Liver transplantation | 0 Participants |
| A4250 High Dose | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | Biliary diversion surgery | 0 Participants |
| A4250 High Dose | Number of Participants Underwent Biliary Diversion Surgery and Liver Transplantation | Liver transplantation | 0 Participants |
Secondary
Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period
A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based 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 only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively.
Time frame: From Baseline (Day 1) up to Week 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 8 | 34.38 percentage of assessments | Standard Error 7.29 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 8 | 31.07 percentage of assessments | Standard Error 5.213 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 4 | 33.48 percentage of assessments | Standard Error 5.881 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 4 | 35.89 percentage of assessments | Standard Error 7.055 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 12 | 31.07 percentage of assessments | Standard Error 5.374 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 16 | 30.67 percentage of assessments | Standard Error 5.522 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 24 | 28.17 percentage of assessments | Standard Error 5.276 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 16 | 29.91 percentage of assessments | Standard Error 5.246 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 24 | 29.31 percentage of assessments | Standard Error 6.592 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 20 | 28.50 percentage of assessments | Standard Error 5.206 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 18 | 28.93 percentage of assessments | Standard Error 5.224 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 18 | 30.83 percentage of assessments | Standard Error 6.898 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 18 | 29.88 percentage of assessments | Standard Error 5.462 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 20 | 30.39 percentage of assessments | Standard Error 6.812 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 16 | 31.43 percentage of assessments | Standard Error 7.006 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 20 | 29.45 percentage of assessments | Standard Error 5.376 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 12 | 32.35 percentage of assessments | Standard Error 5.945 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 12 | 33.63 percentage of assessments | Standard Error 7.404 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 4 | 31.07 percentage of assessments | Standard Error 5.436 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 8 | 32.72 percentage of assessments | Standard Error 5.871 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 18 | 61.25 percentage of assessments | Standard Error 6.225 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 4 | 51.40 percentage of assessments | Standard Error 5.818 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 8 | 54.23 percentage of assessments | Standard Error 5.887 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 12 | 58.85 percentage of assessments | Standard Error 5.738 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 16 | 58.83 percentage of assessments | Standard Error 5.925 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 18 | 58.80 percentage of assessments | Standard Error 6.004 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 20 | 58.68 percentage of assessments | Standard Error 6.079 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 4 | 48.14 percentage of assessments | Standard Error 6.161 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 8 | 51.16 percentage of assessments | Standard Error 6.129 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 12 | 56.06 percentage of assessments | Standard Error 5.922 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 16 | 56.41 percentage of assessments | Standard Error 6.183 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 18 | 56.35 percentage of assessments | Standard Error 6.249 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 20 | 56.27 percentage of assessments | Standard Error 6.293 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 24 | 55.73 percentage of assessments | Standard Error 6.396 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 4 | 54.66 percentage of assessments | Standard Error 6.594 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 8 | 57.30 percentage of assessments | Standard Error 6.478 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 12 | 61.65 percentage of assessments | Standard Error 6.33 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 16 | 61.26 percentage of assessments | Standard Error 6.205 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 20 | 61.09 percentage of assessments | Standard Error 6.284 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 24 | 60.89 percentage of assessments | Standard Error 6.385 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 8 | 48.21 percentage of assessments | Standard Error 7.479 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 4 | 37.59 percentage of assessments | Standard Error 7.629 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 4 | 47.37 percentage of assessments | Standard Error 8.439 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 24 | 46.47 percentage of assessments | Standard Error 8.456 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 8 | 44.64 percentage of assessments | Standard Error 7.804 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 20 | 48.10 percentage of assessments | Standard Error 7.975 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 20 | 46.47 percentage of assessments | Standard Error 8.434 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 12 | 46.05 percentage of assessments | Standard Error 7.884 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 18 | 48.25 percentage of assessments | Standard Error 7.809 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 4 | 42.48 percentage of assessments | Standard Error 7.508 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 16 | 46.15 percentage of assessments | Standard Error 8.178 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 16 | 48.31 percentage of assessments | Standard Error 7.624 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 18 | 49.92 percentage of assessments | Standard Error 7.8 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 16 | 50.47 percentage of assessments | Standard Error 7.66 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 12 | 49.15 percentage of assessments | Standard Error 7.428 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 20 | 49.74 percentage of assessments | Standard Error 7.993 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 12 | 52.26 percentage of assessments | Standard Error 7.693 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 18 | 46.57 percentage of assessments | Standard Error 8.363 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 24 | 48.92 percentage of assessments | Standard Error 8.197 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 8 | 51.79 percentage of assessments | Standard Error 8.001 |
Secondary
Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period
A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based 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 only when more than 50% of planned assessment recorded by each participant multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively.
Time frame: Baseline (Day 1) and Weeks 1 to 4, Weeks 5 to 8, Weeks 9 to 12, Weeks 13 to 16, Weeks 17 to 20, and Weeks 21 to 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 17 to 20 | 32.62 percentage of assessments | Standard Error 8.583 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 5 to 8 | 31.96 percentage of assessments | Standard Error 6.515 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 9 to 12 | 31.61 percentage of assessments | Standard Error 6.794 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 13 to 16 | 28.36 percentage of assessments | Standard Error 7.534 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 1 to 4 | 33.48 percentage of assessments | Standard Error 5.881 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 21 to 24 | 35.42 percentage of assessments | Standard Error 8.783 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 1 to 4 | 31.07 percentage of assessments | Standard Error 5.436 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 5 to 8 | 31.07 percentage of assessments | Standard Error 5.812 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 9 to 12 | 31.07 percentage of assessments | Standard Error 6.747 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 13 to 16 | 29.62 percentage of assessments | Standard Error 8.502 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 17 to 20 | 30.24 percentage of assessments | Standard Error 8.733 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 21 to 24 | 37.30 percentage of assessments | Standard Error 10.909 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 1 to 4 | 35.89 percentage of assessments | Standard Error 7.055 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 5 to 8 | 32.86 percentage of assessments | Standard Error 8.138 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 9 to 12 | 32.14 percentage of assessments | Standard Error 8.078 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 13 to 16 | 27.10 percentage of assessments | Standard Error 8.997 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 17 to 20 | 35.00 percentage of assessments | Standard Error 10.323 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 21 to 24 | 33.54 percentage of assessments | Standard Error 9.699 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 21 to 24 | 72.76 percentage of assessments | Standard Error 7.185 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 1 to 4 | 51.40 percentage of assessments | Standard Error 5.818 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 13 to 16 | 66.07 percentage of assessments | Standard Error 8.042 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 1 to 4 | 54.66 percentage of assessments | Standard Error 6.594 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 5 to 8 | 57.07 percentage of assessments | Standard Error 6.714 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 9 to 12 | 70.34 percentage of assessments | Standard Error 6.816 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 13 to 16 | 69.11 percentage of assessments | Standard Error 7.783 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 9 to 12 | 68.09 percentage of assessments | Standard Error 6.357 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 17 to 20 | 64.11 percentage of assessments | Standard Error 8.121 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 17 to 20 | 69.46 percentage of assessments | Standard Error 7.848 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 13 to 16 | 67.59 percentage of assessments | Standard Error 7.779 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 9 to 12 | 65.84 percentage of assessments | Standard Error 6.854 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 5 to 8 | 59.94 percentage of assessments | Standard Error 7.355 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 17 to 20 | 66.79 percentage of assessments | Standard Error 7.805 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 5 to 8 | 54.19 percentage of assessments | Standard Error 6.783 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 21 to 24 | 64.37 percentage of assessments | Standard Error 7.324 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 21 to 24 | 68.57 percentage of assessments | Standard Error 6.926 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 1 to 4 | 48.14 percentage of assessments | Standard Error 6.161 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 21 to 24 | 55.12 percentage of assessments | Standard Error 10.047 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 1 to 4 | 47.37 percentage of assessments | Standard Error 8.439 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 5 to 8 | 56.20 percentage of assessments | Standard Error 8.483 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 9 to 12 | 51.39 percentage of assessments | Standard Error 10.015 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 9 to 12 | 55.95 percentage of assessments | Standard Error 9.383 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 21 to 24 | 55.90 percentage of assessments | Standard Error 9.976 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 13 to 16 | 53.57 percentage of assessments | Standard Error 9.55 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 17 to 20 | 55.58 percentage of assessments | Standard Error 11.171 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 13 to 16 | 55.13 percentage of assessments | Standard Error 10.664 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 21 to 24 | 54.35 percentage of assessments | Standard Error 10.801 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 1 to 4 | 42.48 percentage of assessments | Standard Error 7.508 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 5 to 8 | 53.95 percentage of assessments | Standard Error 8.423 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 1 to 4 | 37.59 percentage of assessments | Standard Error 7.629 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 9 to 12 | 53.67 percentage of assessments | Standard Error 9.404 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 13 to 16 | 54.35 percentage of assessments | Standard Error 9.802 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 17 to 20 | 56.14 percentage of assessments | Standard Error 10.655 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 5 to 8 | 51.69 percentage of assessments | Standard Error 9.051 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo ObsRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 17 to 20 | 56.70 percentage of assessments | Standard Error 10.554 |
Secondary
Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period
A positive pruritus assessment was defined as a scratching score of \<=1 or at least 1 point drop from baseline based on the Albireo PRO instrument, only participants \>=8 years of age completed the Albireo PRO instrument. The percentage 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 multiplied by 100. At each assessment, the AM or PM score was compared to the baseline AM or PM average, respectively.
Time frame: From Baseline (Day 1) up to Week 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 4 | 55.36 percentage of assessments | Standard Error 8.929 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 4 | 64.29 percentage of assessments | Standard Error 8.929 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 4 | 73.21 percentage of assessments | Standard Error 8.929 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 8 | 39.29 percentage of assessments | Standard Error 14.286 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 16 | 38.62 percentage of assessments | Standard Error 3.348 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 24 | 26.19 percentage of assessments | Standard Error 1.19 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 12 | 33.93 percentage of assessments | Standard Error 10.119 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 24 | 37.20 percentage of assessments | Standard Error 2.083 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 20 | 28.93 percentage of assessments | Standard Error 0.357 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 16 | 31.70 percentage of assessments | Standard Error 1.339 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 18 | 43.65 percentage of assessments | Standard Error 1.587 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 18 | 31.35 percentage of assessments | Standard Error 1.19 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 18 | 37.50 percentage of assessments | Standard Error 0.198 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 20 | 40.71 percentage of assessments | Standard Error 0 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 16 | 45.54 percentage of assessments | Standard Error 5.357 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 20 | 34.82 percentage of assessments | Standard Error 0.179 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 12 | 41.96 percentage of assessments | Standard Error 10.417 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 12 | 50.00 percentage of assessments | Standard Error 10.714 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 24 | 31.70 percentage of assessments | Standard Error 1.637 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 8 | 46.88 percentage of assessments | Standard Error 12.946 |
| Placebo | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 8 | 54.46 percentage of assessments | Standard Error 11.607 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 18 | 68.65 percentage of assessments | Standard Error 24.206 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 4 | 43.75 percentage of assessments | Standard Error 25.893 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 8 | 52.68 percentage of assessments | Standard Error 25.893 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 12 | 63.39 percentage of assessments | Standard Error 18.155 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 16 | 66.74 percentage of assessments | Standard Error 18.08 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 18 | 67.66 percentage of assessments | Standard Error 18.849 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 20 | 67.32 percentage of assessments | Standard Error 20.179 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 24 | 68.88 percentage of assessments | Standard Error 19.772 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 4 | 41.07 percentage of assessments | Standard Error 23.214 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 8 | 50.00 percentage of assessments | Standard Error 21.429 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 12 | 61.31 percentage of assessments | Standard Error 11.31 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 16 | 65.18 percentage of assessments | Standard Error 12.5 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 18 | 66.67 percentage of assessments | Standard Error 13.492 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 20 | 66.07 percentage of assessments | Standard Error 15.357 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 24 | 66.72 percentage of assessments | Standard Error 16.718 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 4 | 46.43 percentage of assessments | Standard Error 28.571 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 8 | 55.36 percentage of assessments | Standard Error 30.357 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 12 | 65.48 percentage of assessments | Standard Error 25 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 16 | 68.30 percentage of assessments | Standard Error 23.661 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 20 | 68.57 percentage of assessments | Standard Error 25 |
| A4250 Low Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 24 | 71.04 percentage of assessments | Standard Error 22.825 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 4 | 37.86 percentage of assessments | Standard Error 16.115 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 8 | 41.96 percentage of assessments | Standard Error 16.178 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 4 | 40.00 percentage of assessments | Standard Error 15.042 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 24 | 47.65 percentage of assessments | Standard Error 17.997 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 24 | 52.06 percentage of assessments | Standard Error 19.595 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 8 | 45.00 percentage of assessments | Standard Error 16.545 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 20 | 48.07 percentage of assessments | Standard Error 18.01 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 20 | 52.43 percentage of assessments | Standard Error 19.568 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 12 | 48.57 percentage of assessments | Standard Error 17.715 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 18 | 47.14 percentage of assessments | Standard Error 17.558 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 4 | 38.93 percentage of assessments | Standard Error 15.272 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 16 | 51.25 percentage of assessments | Standard Error 18.751 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 16 | 42.68 percentage of assessments | Standard Error 16.554 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 16 | 46.96 percentage of assessments | Standard Error 17.477 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 18 | 42.22 percentage of assessments | Standard Error 16.343 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 12 | 41.43 percentage of assessments | Standard Error 16.562 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM and PM scores combined: Weeks 0 to 12 | 45.00 percentage of assessments | Standard Error 16.939 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 20 | 43.71 percentage of assessments | Standard Error 16.86 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 8 | 38.93 percentage of assessments | Standard Error 16.243 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | PM score: Weeks 0 to 18 | 52.06 percentage of assessments | Standard Error 19.23 |
| A4250 High Dose | Percentage of Individual Assessments Meeting the Definition of a Positive Pruritus Assessment at the Participant Level Using the Albireo PRO Instrument Over the 24-Week Treatment Period | AM score: Weeks 0 to 24 | 43.24 percentage of assessments | Standard Error 16.835 |
Secondary
Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24
The responder for pruritus scores was defined as a participant who achieved at least a 1-point reduction in the ObsRO pruritus score. Percentages are rounded to hundredth decimal.
Time frame: Weeks 12 and 24
Population: The FAS included all randomized participants who received at least 1 dose of study treatment. Only participants with data collected at specific timepoints are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 12 (Bi-weekly score) | 5.0 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 12 (Monthly score) | 10.0 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 24 (Bi-weekly score) | 11.8 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 24 (Monthly score) | 10.5 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 12 (Bi-weekly score) | 10.0 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 12 (Monthly score) | 10.0 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 24 (Bi-weekly score) | 11.8 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 24 (Monthly score) | 15.8 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 12 (Bi-weekly score) | 10.0 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 12 (Monthly score) | 10.0 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 24 (Bi-weekly score) | 11.8 percentage of participants |
| Placebo | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 24 (Monthly score) | 10.5 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 24 (Monthly score) | 52.2 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 12 (Bi-weekly score) | 60.9 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 24 (Bi-weekly score) | 39.1 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 12 (Bi-weekly score) | 65.2 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 12 (Monthly score) | 52.2 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 12 (Monthly score) | 56.5 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 24 (Bi-weekly score) | 56.5 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 24 (Bi-weekly score) | 43.5 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 24 (Monthly score) | 52.2 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 12 (Bi-weekly score) | 60.9 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 24 (Monthly score) | 52.2 percentage of participants |
| A4250 Low Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 12 (Monthly score) | 60.9 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 24 (Monthly score) | 31.6 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 12 (Bi-weekly score) | 42.1 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 12 (Monthly score) | 36.8 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 12 (Monthly score) | 42.1 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 24 (Bi-weekly score) | 33.3 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM score: Week 24 (Monthly score) | 42.1 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 24 (Bi-weekly score) | 33.3 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 12 (Bi-weekly score) | 42.1 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 12 (Monthly score) | 42.1 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 12 (Bi-weekly score) | 36.8 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | AM and PM scores combined: Week 24 (Bi-weekly score) | 33.3 percentage of participants |
| A4250 High Dose | Percentage of Responders for Pruritus Assessments Based on Bi-Weekly and Monthly Scores Using the Albireo Observer-Reported Outcome Instrument at Weeks 12 and 24 | PM score: Week 24 (Monthly score) | 31.6 percentage of participants |