Primary Biliary Cirrhosis (PBC)
Conditions
Keywords
PBC
Brief summary
The primary objective of this study is to evaluate the effect of seladelpar (MBX-8025) on alkaline phosphatase (AP) levels in participants with primary biliary cirrhosis (PBC).
Detailed description
Primary: To evaluate the effect of MBX-8025 on Alkaline Phosphatase (AP) levels Secondary: To evaluate the safety and tolerability of MBX-8025 in subjects with Primary Biliary Cirrhosis (PBC) To evaluate the effects of MBX-8025 on Primary Biliary Cirrhosis (PBC) response criteria To evaluate the effects of MBX-8025 on other markers of liver function, lipids, pruritus and Quality of Life (QoL)
Interventions
DRUGPlacebo Comparator
Placebo Capsule
DRUGExperimental: Seladelpar 50 mg
Seladelpar 50 mg capsule
DRUGExperimental: Seladelpar / MBX-8025 200 mg
Seladelpar 100 mg capsules
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Must have given written informed consent (signed and dated) and any authorizations required by local law 2. 18 to 75 years old (inclusive) 3. Male or female with a diagnosis of PBC, by at least two of the following criteria: * History of AP above upper limit of normal (ULN) for at least six months * Positive Anti-Mitochondrial Antibodies (AMA) titers (\>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies * Documented liver biopsy result consistent with PBC 4. On a stable and recommended dose of UDCA for the past twelve months 5. AP ≥ 1.67 × ULN 6. For females of reproductive potential, use of at least one barrier contraceptive and a second effective birth control method during the study and for at least two weeks after the last dose. For male subjects, use of appropriate contraception (e.g., condoms), so their female partners of reproductive potential do not become pregnant during the study and for at least two weeks after the last dose
Exclusion criteria
1. A medical condition, other than PBC, that in the investigator's opinion would preclude full participation in the study or confound its results (e.g., cancer on active treatment) 2. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \> 3 × ULN 3. Total bilirubin \> 2 × ULN 4. Auto-immune hepatitis 5. Primary sclerosing cholangitis 6. Known history of alpha-1-Antitrypsin deficiency 7. Known history of chronic viral hepatitis 8. Creatine kinase above ULN 9. Serum creatinine above ULN 10. For females, pregnancy or breast-feeding 11. Use of colchicine, methotrexate, azathioprine, or systemic steroids in the two months preceding screening 12. Current use of fibrates, including fenofibrates, or simvastatin 13. Use of an experimental treatment for PBC 14. Use of experimental or unapproved immunosuppressant 15. Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Alkaline Phosphatase (AP) Levels | Baseline | Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0). |
| Percent Change From Baseline in Alkaline Phosphatase (AP) Levels | Baseline, Week 12 | Percent change in AP serum levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by last observation carried forward (LOCF). Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin | Week 12 | Participants were defined as responders for the composite endpoint of AP and total bilirubin if their AP level was \<1.67 × upper limit of normal (ULN) and had decreased at least 15% from their Baseline level and their total bilirubin value was within the normal range \[0.1-1.1 milligrams/deciliter (mg/dL)\]. |
| Percent Change From Baseline in Gamma-glutamyl Transferase (GGT) | Baseline, Week 12 | Percentage change in GGT levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for GGT level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in 5'Nucleotidase (5NT) | Baseline, Week 12 | Percentage change in 5'Nucleotidase levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for 5NT level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Total Bilirubin | Baseline, Week 12 | Percentage change in total bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for total bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Conjugated Bilirubin | Baseline, Week 12 | Percentage change in conjugated bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for conjugated bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Unconjugated Bilirubin | Baseline, Week 12 | Percentage change in unconjugated bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for unconjugated bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Bone-specific AP Levels | Baseline, Week 12 | Percentage change in bone-specific AP levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for bone-specific level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Triglycerides (TG) | Baseline, Week 12 | Percentage change in TG levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for TG level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Total Cholesterol (TC) | Baseline, Week 12 | Percentage change in TC levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for TC level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Aspartate Aminotransferase (AST) | Baseline, Week 12 | Percentage change in AST levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for AST level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Baseline, Week 12 | Percentage change in LDL-C levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for LDL-C level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I) | Week 12 | Published criteria for response to treatment in PBC included Paris I criteria. For Paris I, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 3x ULN and AST ≤ 2x ULN and Total Bilirubin ≤ 1 mg/dL. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF. |
| Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II) | Week 12 | Published criteria for response to treatment in PBC included Paris II criteria. For Paris II, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.5x ULN and AST ≤ 1.5x ULN and Total Bilirubin ≤ 1 mg/dL. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF. |
| Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I) | Week 12 | Published criteria for response to treatment in PBC included Toronto I criteria. For Toronto I, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.67x ULN. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF. |
| Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II) | Week 12 | Published criteria for response to treatment in PBC included Toronto II criteria. For Toronto II, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.76x ULN. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF. |
| United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | Week 12 | The UK-PBC Risk Score was used to estimate the risk that a PBC participant would develop liver failure that would require liver transplantation within 5, 10 or 15 years from diagnosis. The UK-PBC Risk Score calculation was adapted based on the AP assessment, transaminases (refers to the ALT, where available, otherwise the AST assessment) and total bilirubin assessment respectively at end of treatment divided by its upper limits of the corresponding normal ranges; albumin and platelet refer to the baseline values of these parameters divided by their corresponding lower limits of normal ranges. Missing assessments at end of treatment was imputed by last observation carried forward (LOCF). The UK-PBC risk scores for 5, 10 and 15 years was calculated for each treatment group |
| Change From Baseline in 5-Dimension (5-D) Itch Scale Score | Baseline, Week 12 | The 5-D itch scale was used to for the multidimensional quantification of pruritus over time. It assessed five aspects of itching: degree, duration, direction, disability, and distribution.The 5-D itch Scale is a measure of itching that has been validated in patients with chronic pruritus to detect changes over time. A 5-D itch scale score typically ranges from 5 to 25 with a higher score indicating greater itch severity, where 5 represents no pruritus (itching) and 25 represents the most severe pruritus; Each dimension is scored separately, and the scores are added together to get a total 5-D itch score. Higher scores indicate worsening of itching. The total 5-D itch Scale score change from Baseline was calculated. Baseline for 5-D itch scale was defined as the last non-missing assessments prior to or on the date of the first study dose. Missing assessments at end of treatment was imputed by LOCF. |
| Change From Baseline in Pruritus Visual Analog Scale (VAS) Score | Baseline, Week 12 | VAS was used to measure pruritis in participants with PBC. Participants placed a mark representing their level of itching since the previous measurement on a 100-mm VAS with 0 indicating no itching and 100 mm indicating the worst possible itching. Higher scores indicated worsening of itching The change from Baseline was presented by treatment group. Baseline for VAS score was defined as the last non-missing assessments prior to or on the date of the first study dose. Missing assessments at end of treatment was imputed by LOCF. |
| Change From Baseline in PBC-40 Quality of Life Questionnaire | Baseline, Week 12 | The PBC-40 questionnaire was used to evaluate health-related quality of life measures, specifically fatigue. The PBC-40 questionnaire is a disease-specific tool developed to specifically measure the psychometric profile of PBC patients. It consists of 40 items divided into the six domains relevant to PBC including Cognitive, Social, EmotionalFunction, Fatigue, Itch, and Other Symptoms/General Questions. Items are scored from 1 to 5 and individual items scores are summed to give a total domain score. PBC 40 QoL domain score ranges are:Cognitive (6-30), Emotional Function (3-15),Fatigue (11-55), Itch (3-15),Social (10-50),Symptoms (7-35).Higher scores represent high impact and lower scores low impact of PBC on quality of life.The change and percentage change from Baseline for individual domain score at end of treatment were reported. Baseline for PBC-40 questionnaire was the last non-missing assessments prior to or on the date of the first study dose.Missing assessments imputed by LOCF. |
| Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | Baseline, Week 12 | Percentage change in HDL-C levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for HDL-C level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
| Percent Change From Baseline in Alanine Aminotransferase (ALT) | Baseline, Week 12 | Percentage change in ALT levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for ALT level was defined as the last non-missing assessments prior to or on the date of the first study dose. |
Countries
Canada, Germany, Poland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Canada, Germany, the United Kingdom, and the United States.
Pre-assignment details
70 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Seladelpar 200 mg Participants received seladelpar 200 mg capsules (2 x 100 mg capsules), orally, once daily for 12 weeks. | 12 |
| Seladelpar 50 mg Participants received seladelpar 50 mg capsule (1 x 50 mg capsule) and a PTM seladelpar capsule, orally, once daily for 12 weeks. | 13 |
| Placebo Participants received 2 PTM seladelpar capsules, orally, once daily for 12 weeks. | 13 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 0 |
| Overall Study | Randomized but never treated | 1 | 1 | 1 |
| Overall Study | Reason not specified | 6 | 9 | 9 |
| Overall Study | Withdrawal of informed consent | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Seladelpar 200 mg | Seladelpar 50 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 12 Participants | 12 Participants | 33 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 11.4 | 54 years STANDARD_DEVIATION 7.4 | 55 years STANDARD_DEVIATION 10.1 | 55 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 12 Participants | 13 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 12 Participants | 13 Participants | 35 Participants |
| Region of Enrollment Canada | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Germany | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Region of Enrollment United States | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 12 Participants | 36 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 10 / 12 | 11 / 13 | 10 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Baseline Alkaline Phosphatase (AP) Levels
Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).
Time frame: Baseline
Population: The modified intent-to-treat (mITT) Analysis Set was defined as any randomized participant who received at least 1 dose of medication and had at least 1 on-treatment AP evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Baseline Alkaline Phosphatase (AP) Levels | 248.3 units per liter (U/L) | Standard Deviation 88.69 |
| Seladelpar 50 mg | Baseline Alkaline Phosphatase (AP) Levels | 311.6 units per liter (U/L) | Standard Deviation 94.83 |
| Placebo | Baseline Alkaline Phosphatase (AP) Levels | 232.8 units per liter (U/L) | Standard Deviation 72.51 |
Primary
Percent Change From Baseline in Alkaline Phosphatase (AP) Levels
Percent change in AP serum levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by last observation carried forward (LOCF). Baseline for AP level was defined as the mean between assessments at Visit 1 (Week -4 to Week 0) and Visit 2 (Week 0).
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Alkaline Phosphatase (AP) Levels | -62.83 percent change in AP levels | Standard Error 4.312 |
| Seladelpar 50 mg | Percent Change From Baseline in Alkaline Phosphatase (AP) Levels | -53.21 percent change in AP levels | Standard Error 3.961 |
| Placebo | Percent Change From Baseline in Alkaline Phosphatase (AP) Levels | -1.84 percent change in AP levels | Standard Error 4.02 |
p-value: <0.000195% CI: [-72.85, -49.13]ANCOVA
p-value: <0.000195% CI: [-63.3, -39.44]ANCOVA
p-value: 0.116795% CI: [-21.79, 2.54]ANCOVA
Secondary
Change From Baseline in 5-Dimension (5-D) Itch Scale Score
The 5-D itch scale was used to for the multidimensional quantification of pruritus over time. It assessed five aspects of itching: degree, duration, direction, disability, and distribution.The 5-D itch Scale is a measure of itching that has been validated in patients with chronic pruritus to detect changes over time. A 5-D itch scale score typically ranges from 5 to 25 with a higher score indicating greater itch severity, where 5 represents no pruritus (itching) and 25 represents the most severe pruritus; Each dimension is scored separately, and the scores are added together to get a total 5-D itch score. Higher scores indicate worsening of itching. The total 5-D itch Scale score change from Baseline was calculated. Baseline for 5-D itch scale was defined as the last non-missing assessments prior to or on the date of the first study dose. Missing assessments at end of treatment was imputed by LOCF.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Change From Baseline in 5-Dimension (5-D) Itch Scale Score | -0.9 score on a scale | Standard Error 1.31 |
| Seladelpar 50 mg | Change From Baseline in 5-Dimension (5-D) Itch Scale Score | 0.5 score on a scale | Standard Error 1.15 |
| Placebo | Change From Baseline in 5-Dimension (5-D) Itch Scale Score | 0.2 score on a scale | Standard Error 1.25 |
p-value: 0.537995% CI: [-4.8, 2.6]ANCOVA
p-value: 0.894995% CI: [-3.3, 3.7]ANCOVA
p-value: 0.443195% CI: [-4.9, 2.2]ANCOVA
Secondary
Change From Baseline in PBC-40 Quality of Life Questionnaire
The PBC-40 questionnaire was used to evaluate health-related quality of life measures, specifically fatigue. The PBC-40 questionnaire is a disease-specific tool developed to specifically measure the psychometric profile of PBC patients. It consists of 40 items divided into the six domains relevant to PBC including Cognitive, Social, EmotionalFunction, Fatigue, Itch, and Other Symptoms/General Questions. Items are scored from 1 to 5 and individual items scores are summed to give a total domain score. PBC 40 QoL domain score ranges are:Cognitive (6-30), Emotional Function (3-15),Fatigue (11-55), Itch (3-15),Social (10-50),Symptoms (7-35).Higher scores represent high impact and lower scores low impact of PBC on quality of life.The change and percentage change from Baseline for individual domain score at end of treatment were reported. Baseline for PBC-40 questionnaire was the last non-missing assessments prior to or on the date of the first study dose.Missing assessments imputed by LOCF.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Seladelpar 200 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Cognitive Domain Score | 2.6 score on a scale | Standard Error 0.96 |
| Seladelpar 200 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Social Domain Score | 3.2 score on a scale | Standard Error 1.32 |
| Seladelpar 200 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Emotional Function Domain Score | 0.4 score on a scale | Standard Error 0.73 |
| Seladelpar 200 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Fatigue Domain Score | -0.3 score on a scale | Standard Error 1.5 |
| Seladelpar 200 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Itch Domain Score | -0.6 score on a scale | Standard Error 0.81 |
| Seladelpar 200 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Symptoms Domain Score | 1.1 score on a scale | Standard Error 0.76 |
| Seladelpar 50 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Symptoms Domain Score | 0.9 score on a scale | Standard Error 0.62 |
| Seladelpar 50 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Cognitive Domain Score | 0.9 score on a scale | Standard Error 0.76 |
| Seladelpar 50 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Fatigue Domain Score | 2.3 score on a scale | Standard Error 1.2 |
| Seladelpar 50 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Itch Domain Score | 0.3 score on a scale | Standard Error 0.65 |
| Seladelpar 50 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Social Domain Score | 0.3 score on a scale | Standard Error 1.06 |
| Seladelpar 50 mg | Change From Baseline in PBC-40 Quality of Life Questionnaire | Emotional Function Domain Score | 0.4 score on a scale | Standard Error 0.58 |
| Placebo | Change From Baseline in PBC-40 Quality of Life Questionnaire | Social Domain Score | -0.5 score on a scale | Standard Error 1.09 |
| Placebo | Change From Baseline in PBC-40 Quality of Life Questionnaire | Emotional Function Domain Score | 0.0 score on a scale | Standard Error 0.62 |
| Placebo | Change From Baseline in PBC-40 Quality of Life Questionnaire | Symptoms Domain Score | -1.5 score on a scale | Standard Error 0.64 |
| Placebo | Change From Baseline in PBC-40 Quality of Life Questionnaire | Fatigue Domain Score | -1.9 score on a scale | Standard Error 1.26 |
| Placebo | Change From Baseline in PBC-40 Quality of Life Questionnaire | Cognitive Domain Score | -0.8 score on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline in PBC-40 Quality of Life Questionnaire | Itch Domain Score | -0.4 score on a scale | Standard Error 0.67 |
Comparison: Cognitive Domain Scorep-value: 0.011595% CI: [0.8, 6]ANCOVA
Comparison: Cognitive Domain Scorep-value: 0.125695% CI: [-0.5, 4]ANCOVA
Comparison: Cognitive Domain Scorep-value: 0.184295% CI: [-0.9, 4.2]ANCOVA
Comparison: Social Domain Scorep-value: 0.04295% CI: [0.1, 7.2]ANCOVA
Comparison: Social Domain Scorep-value: 0.638495% CI: [-2.4, 3.9]ANCOVA
Comparison: Social Domain Scorep-value: 0.103595% CI: [-0.6, 6.5]ANCOVA
Comparison: Emotional Function Domain Scorep-value: 0.696795% CI: [-1.6, 2.4]ANCOVA
Comparison: Emotional Function Domain Scorep-value: 0.616495% CI: [-1.3, 2.2]ANCOVA
Comparison: Emotional Function Domain Scorep-value: 0.954895% CI: [-2, 1.9]ANCOVA
Comparison: Itch Domain Scorep-value: 0.828695% CI: [-2.4, 1.9]ANCOVA
Comparison: Fatigue Domain Scorep-value: 0.022695% CI: [0.6, 7.8]ANCOVA
Comparison: Fatigue Domain Scorep-value: 0.186195% CI: [-6.6, 1.4]ANCOVA
Comparison: Fatigue Domain Scorep-value: 0.415995% CI: [-2.4, 5.7]ANCOVA
Comparison: Itch Domain Scorep-value: 0.484895% CI: [-1.3, 2.6]ANCOVA
Comparison: Itch Domain Scorep-value: 0.404895% CI: [-3.1, 1.3]ANCOVA
Comparison: Symptoms Domain Scorep-value: 0.014195% CI: [0.6, 4.7]ANCOVA
Comparison: Symptoms Domain Scorep-value: 0.013895% CI: [0.5, 4.2]ANCOVA
Comparison: Symptoms Domain Scorep-value: 0.791195% CI: [-1.8, 2.3]ANCOVA
Secondary
Change From Baseline in Pruritus Visual Analog Scale (VAS) Score
VAS was used to measure pruritis in participants with PBC. Participants placed a mark representing their level of itching since the previous measurement on a 100-mm VAS with 0 indicating no itching and 100 mm indicating the worst possible itching. Higher scores indicated worsening of itching The change from Baseline was presented by treatment group. Baseline for VAS score was defined as the last non-missing assessments prior to or on the date of the first study dose. Missing assessments at end of treatment was imputed by LOCF.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Change From Baseline in Pruritus Visual Analog Scale (VAS) Score | 0.9 score on a scale | Standard Error 7.54 |
| Seladelpar 50 mg | Change From Baseline in Pruritus Visual Analog Scale (VAS) Score | -0.7 score on a scale | Standard Error 6.35 |
| Placebo | Change From Baseline in Pruritus Visual Analog Scale (VAS) Score | 8.3 score on a scale | Standard Error 6.42 |
p-value: 0.467495% CI: [-28, 13.2]ANCOVA
p-value: 0.323695% CI: [-27.4, 9.4]ANCOVA
p-value: 0.872395% CI: [-18.7, 21.9]ANCOVA
Secondary
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I)
Published criteria for response to treatment in PBC included Paris I criteria. For Paris I, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 3x ULN and AST ≤ 2x ULN and Total Bilirubin ≤ 1 mg/dL. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.
Time frame: Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Paris I) was defined as the last non-missing assessments prior to or on the date of the first study dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seladelpar 200 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I) | 2 Participants |
| Seladelpar 50 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I) | 2 Participants |
| Placebo | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris I) | 2 Participants |
p-value: 0.4667Fisher Exact
p-value: 0.4667Fisher Exact
Secondary
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II)
Published criteria for response to treatment in PBC included Paris II criteria. For Paris II, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.5x ULN and AST ≤ 1.5x ULN and Total Bilirubin ≤ 1 mg/dL. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.
Time frame: Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Paris II) was defined as the last non-missing assessments prior to or on the date of the first study dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seladelpar 200 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II) | 5 Participants |
| Seladelpar 50 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II) | 8 Participants |
| Placebo | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Paris II) | 9 Participants |
p-value: 0.0824Fisher Exact
p-value: 0.0537Fisher Exact
p-value: 1Fisher Exact
Secondary
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I)
Published criteria for response to treatment in PBC included Toronto I criteria. For Toronto I, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.67x ULN. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.
Time frame: Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Toronto I) was defined as the last non-missing assessments prior to or on the date of the first study dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seladelpar 200 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I) | 0 Participants |
| Seladelpar 50 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I) | 3 Participants |
| Placebo | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto I) | 7 Participants |
p-value: 0.0101Fisher Exact
p-value: 0.0198Fisher Exact
p-value: 0.5165Fisher Exact
Secondary
Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II)
Published criteria for response to treatment in PBC included Toronto II criteria. For Toronto II, the criteria used to measure the PBC participants' response to study treatment was: AP ≤ 1.76x ULN. Participants who satisfied the criteria were defined as responders and those who did not were considered nonresponders if all the elements had non-missing assessments at that visit. The number of nonresponders were reported, the missing assessments were imputed by LOCF.
Time frame: Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed. Only participants who did not meet the criteria for response at Baseline were included in the analysis. Baseline for published PBC response criteria (Toronto II) was defined as the last non-missing assessments prior to or on the date of the first study dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Seladelpar 200 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II) | 0 Participants |
| Seladelpar 50 mg | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II) | 2 Participants |
| Placebo | Number of Participants Who Were Non-responders as Determined by Published PBC Response Criteria (Toronto II) | 7 Participants |
p-value: 0.0101Fisher Exact
p-value: 0.0055Fisher Exact
p-value: 1Fisher Exact
Secondary
Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin
Participants were defined as responders for the composite endpoint of AP and total bilirubin if their AP level was \<1.67 × upper limit of normal (ULN) and had decreased at least 15% from their Baseline level and their total bilirubin value was within the normal range \[0.1-1.1 milligrams/deciliter (mg/dL)\].
Time frame: Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Seladelpar 200 mg | Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin | 100 percentage of participants |
| Seladelpar 50 mg | Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin | 69.2 percentage of participants |
| Placebo | Percentage of Participants With Response as Determined by Composite Endpoint of Alkaline Phosphatase and Total Bilirubin | 8.3 percentage of participants |
p-value: <0.0001Fisher Exact
p-value: 0.0036Fisher Exact
p-value: 0.1045Fisher Exact
Secondary
Percent Change From Baseline in 5'Nucleotidase (5NT)
Percentage change in 5'Nucleotidase levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for 5NT level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in 5'Nucleotidase (5NT) | -34.35 percent change in 5'Nucleotidase levels | Standard Error 8.446 |
| Seladelpar 50 mg | Percent Change From Baseline in 5'Nucleotidase (5NT) | -24.92 percent change in 5'Nucleotidase levels | Standard Error 7.148 |
| Placebo | Percent Change From Baseline in 5'Nucleotidase (5NT) | -0.08 percent change in 5'Nucleotidase levels | Standard Error 7.305 |
p-value: 0.00595% CI: [-57.4, -11.14]ANCOVA
p-value: 0.019995% CI: [-45.47, -4.21]ANCOVA
p-value: 0.416195% CI: [-32.77, 13.9]ANCOVA
Secondary
Percent Change From Baseline in Alanine Aminotransferase (ALT)
Percentage change in ALT levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for ALT level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT analysis set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) | 181.11 percent change in ALT levels | Standard Error 77.864 |
| Seladelpar 50 mg | Percent Change From Baseline in Alanine Aminotransferase (ALT) | 111.83 percent change in ALT levels | Standard Error 68.061 |
| Placebo | Percent Change From Baseline in Alanine Aminotransferase (ALT) | -4.67 percent change in ALT levels | Standard Error 69.632 |
p-value: 0.084995% CI: [-27.1, 398.66]ANCOVA
p-value: 0.240995% CI: [-82.22, 315.23]ANCOVA
p-value: 0.515495% CI: [-145.47, 284.03]ANCOVA
Secondary
Percent Change From Baseline in Aspartate Aminotransferase (AST)
Percentage change in AST levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for AST level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Aspartate Aminotransferase (AST) | 232.69 percent change in AST levels | Standard Error 77.409 |
| Seladelpar 50 mg | Percent Change From Baseline in Aspartate Aminotransferase (AST) | 130.81 percent change in AST levels | Standard Error 66.933 |
| Placebo | Percent Change From Baseline in Aspartate Aminotransferase (AST) | -2.02 percent change in AST levels | Standard Error 69.364 |
p-value: 0.032295% CI: [21.28, 448.14]ANCOVA
p-value: 0.176495% CI: [-63, 328.65]ANCOVA
p-value: 0.332695% CI: [-109.21, 312.98]ANCOVA
Secondary
Percent Change From Baseline in Bone-specific AP Levels
Percentage change in bone-specific AP levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for bone-specific level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Bone-specific AP Levels | -50.39 percent change in bone-specific AP level | Standard Error 4.837 |
| Seladelpar 50 mg | Percent Change From Baseline in Bone-specific AP Levels | -39.09 percent change in bone-specific AP level | Standard Error 4.355 |
| Placebo | Percent Change From Baseline in Bone-specific AP Levels | -4.43 percent change in bone-specific AP level | Standard Error 4.544 |
p-value: <0.000195% CI: [-47.83, -21.48]ANCOVA
p-value: <0.000195% CI: [-59.5, -32.42]ANCOVA
p-value: 0.092495% CI: [-24.58, 1.97]ANCOVA
Secondary
Percent Change From Baseline in Conjugated Bilirubin
Percentage change in conjugated bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for conjugated bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Conjugated Bilirubin | 42.30 percent change in conjugated bilirubin | Standard Error 10.213 |
| Seladelpar 50 mg | Percent Change From Baseline in Conjugated Bilirubin | 2.00 percent change in conjugated bilirubin | Standard Error 8.932 |
| Placebo | Percent Change From Baseline in Conjugated Bilirubin | 10.84 percent change in conjugated bilirubin | Standard Error 9.296 |
p-value: 0.0395% CI: [3.26, 59.67]ANCOVA
p-value: 0.497995% CI: [-35.11, 17.44]ANCOVA
p-value: 0.005895% CI: [12.58, 68.02]ANCOVA
Secondary
Percent Change From Baseline in Gamma-glutamyl Transferase (GGT)
Percentage change in GGT levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for GGT level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Gamma-glutamyl Transferase (GGT) | -47.17 percent change in GGT levels | Standard Error 9.084 |
| Seladelpar 50 mg | Percent Change From Baseline in Gamma-glutamyl Transferase (GGT) | -42.60 percent change in GGT levels | Standard Error 7.796 |
| Placebo | Percent Change From Baseline in Gamma-glutamyl Transferase (GGT) | -1.83 percent change in GGT levels | Standard Error 7.889 |
p-value: 0.000795% CI: [-70.04, -20.64]ANCOVA
p-value: 0.000895% CI: [-63.28, -18.28]ANCOVA
p-value: 0.715595% CI: [-29.85, 20.73]ANCOVA
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C)
Percentage change in HDL-C levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for HDL-C level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | -13.06 percent change in HDL-C levels | Standard Error 4.326 |
| Seladelpar 50 mg | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | 3.44 percent change in HDL-C levels | Standard Error 3.747 |
| Placebo | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) | 4.33 percent change in HDL-C levels | Standard Error 3.884 |
p-value: 0.005795% CI: [-29.32, -5.46]ANCOVA
p-value: 0.870395% CI: [-11.85, 10.08]ANCOVA
p-value: 0.007695% CI: [-28.3, -4.71]ANCOVA
Secondary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Percentage change in LDL-C levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for LDL-C level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | -17.63 percent change in LDL-C levels | Standard Error 4.372 |
| Seladelpar 50 mg | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | -12.83 percent change in LDL-C levels | Standard Error 3.763 |
| Placebo | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | -2.78 percent change in LDL-C levels | Standard Error 3.958 |
p-value: 0.018695% CI: [-27.05, -2.66]ANCOVA
p-value: 0.074595% CI: [-21.17, 1.06]ANCOVA
p-value: 0.413195% CI: [-16.6, 7]ANCOVA
Secondary
Percent Change From Baseline in Total Bilirubin
Percentage change in total bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for total bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Total Bilirubin | 1.40 percent change in total bilirubin levels | Standard Error 6.384 |
| Seladelpar 50 mg | Percent Change From Baseline in Total Bilirubin | -16.79 percent change in total bilirubin levels | Standard Error 5.586 |
| Placebo | Percent Change From Baseline in Total Bilirubin | -4.79 percent change in total bilirubin levels | Standard Error 5.793 |
p-value: 0.47895% CI: [-11.4, 23.79]ANCOVA
p-value: 0.145995% CI: [-28.4, 4.41]ANCOVA
p-value: 0.040795% CI: [0.82, 35.57]ANCOVA
Secondary
Percent Change From Baseline in Total Cholesterol (TC)
Percentage change in TC levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for TC level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Total Cholesterol (TC) | -16.43 percent change in TC levels | Standard Error 3.25 |
| Seladelpar 50 mg | Percent Change From Baseline in Total Cholesterol (TC) | -8.44 percent change in TC levels | Standard Error 2.774 |
| Placebo | Percent Change From Baseline in Total Cholesterol (TC) | -0.32 percent change in TC levels | Standard Error 2.905 |
p-value: 0.00195% CI: [-25.16, -7.07]ANCOVA
p-value: 0.050495% CI: [-16.27, 0.02]ANCOVA
p-value: 0.073895% CI: [-16.8, 0.81]ANCOVA
Secondary
Percent Change From Baseline in Triglycerides (TG)
Percentage change in TG levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for TG level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Triglycerides (TG) | -7.11 percent change in TG levels | Standard Error 9.415 |
| Seladelpar 50 mg | Percent Change From Baseline in Triglycerides (TG) | -30.27 percent change in TG levels | Standard Error 8.243 |
| Placebo | Percent Change From Baseline in Triglycerides (TG) | 7.04 percent change in TG levels | Standard Error 8.617 |
p-value: 0.277795% CI: [-40.27, 11.97]ANCOVA
p-value: 0.003995% CI: [-61.67, -12.95]ANCOVA
p-value: 0.073495% CI: [-2.33, 48.65]ANCOVA
Secondary
Percent Change From Baseline in Unconjugated Bilirubin
Percentage change in unconjugated bilirubin levels from Baseline to the end of treatment was analyzed. For missing postbaseline data, the last non-missing postbaseline value on treatment was carried forward, with missing assessments imputed by LOCF. Baseline for unconjugated bilirubin level was defined as the last non-missing assessments prior to or on the date of the first study dose.
Time frame: Baseline, Week 12
Population: Participants in the mITT Analysis Set were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Seladelpar 200 mg | Percent Change From Baseline in Unconjugated Bilirubin | -11.86 percent change in unconjugated bilirubin | Standard Error 6.197 |
| Seladelpar 50 mg | Percent Change From Baseline in Unconjugated Bilirubin | -23.04 percent change in unconjugated bilirubin | Standard Error 5.431 |
| Placebo | Percent Change From Baseline in Unconjugated Bilirubin | -8.89 percent change in unconjugated bilirubin | Standard Error 5.62 |
p-value: 0.724495% CI: [-20.03, 14.08]ANCOVA
p-value: 0.0895% CI: [-30.1, 1.8]ANCOVA
p-value: 0.187495% CI: [-5.73, 28.08]ANCOVA
Secondary
United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score
The UK-PBC Risk Score was used to estimate the risk that a PBC participant would develop liver failure that would require liver transplantation within 5, 10 or 15 years from diagnosis. The UK-PBC Risk Score calculation was adapted based on the AP assessment, transaminases (refers to the ALT, where available, otherwise the AST assessment) and total bilirubin assessment respectively at end of treatment divided by its upper limits of the corresponding normal ranges; albumin and platelet refer to the baseline values of these parameters divided by their corresponding lower limits of normal ranges. Missing assessments at end of treatment was imputed by last observation carried forward (LOCF). The UK-PBC risk scores for 5, 10 and 15 years was calculated for each treatment group
Time frame: Week 12
Population: Participants in the mITT Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Seladelpar 200 mg | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 10 years | 3.9796 percentage risk | Standard Deviation 2.74081 |
| Seladelpar 200 mg | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 5 years | 1.3642 percentage risk | Standard Deviation 0.95452 |
| Seladelpar 200 mg | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 15 years | 6.4392 percentage risk | Standard Deviation 4.36737 |
| Seladelpar 50 mg | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 10 years | 5.2712 percentage risk | Standard Deviation 6.31842 |
| Seladelpar 50 mg | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 5 years | 1.8530 percentage risk | Standard Deviation 2.32301 |
| Seladelpar 50 mg | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 15 years | 8.3379 percentage risk | Standard Deviation 9.57184 |
| Placebo | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 5 years | 3.1102 percentage risk | Standard Deviation 5.1892 |
| Placebo | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 15 years | 12.4804 percentage risk | Standard Deviation 17.05244 |
| Placebo | United Kingdom-Primary Biliary Cirrhosis/Cholangitis (UK-PBC) Risk Score | UK-PBC Risk Score by 10 years | 8.3004 percentage risk | Standard Deviation 12.51699 |