Primary Biliary Cholangitis
Conditions
Keywords
Primary Biliary Cholangitis, Primary Biliary Cirrhosis, PBC, Hepatic Impairment, Cirrhosis, Liver
Brief summary
Study to evaluate the efficacy, safety, and tolerability of investigational drug obeticholic acid (OCA) in combination with the investigational drug bezafibrate (BZF) in participants with Primary Biliary Cholangitis (PBC).
Interventions
DRUGObeticholic acid
5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily
200 mg IR tablet of Bezafibrate once daily for the remainder of the study
DRUGOCA Placebo
One tablet daily for the remainder of the study
DRUGBezafibrate 200 mg Placebo
One tablet daily for the remainder of the study
DRUGBezafibrate 400 MG
400 mg SR tablet of Bezafibrate once daily for the remainder of the study
DRUGBezafibrate 400 mg Placebo
One tablet daily for the remainder of the study
DRUGOCA
OCA one tablet will be administered.
DRUGBezafibrate
Bezafibrate one tablet will be administered.
Sponsors
Intercept Pharmaceuticals
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 No maximum
Healthy volunteers
No
Inclusion criteria
* A definite or probable diagnosis of PBC * Qualifying ALP and/or bilirubin liver biochemistry values * Taking Ursodeoxycholic Acid (UDCA) for at least 12 months or no UDCA for 3 months before Day 1
Exclusion criteria
* History or presence of other concomitant liver diseases * Clinical complications of PBC * History or presence of hepatic decompensating events * Current or history of gallbladder disease * If female, known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating * Treatment with commercially available OCA or other farnesoid X receptor (FXR) agonists, or participation in a previous study involving OCA within 3 months before Screening. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Alkaline Phosphatase (ALP) From Baseline in the Double-Blind Treatment Period | Baseline to Week 12 | Serum samples were collected at scheduled visits during the double-blind treatment period. Changes in ALP over time will be analyzed using a mixed model for repeated measures (MMRM) to assess treatment group effects across study visits. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from Baseline was calculated as post Baseline value minus Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Response Rates of ≥10%, ≥20%, ≥30% and ≥40% Reduction From Baseline in ALP in the Double-Blind Treatment Period | Week 12 | Responders were defined as participants achieving a ≥10%, ≥20%, ≥30%, or ≥40% reduction from baseline in serum ALP at Week 12 with non-responder imputation applied. Baseline ALP was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. The percentage of responders were summarized by treatment group for each response threshold and compared using a Cochran Mantel Haenszel test stratified by the randomization stratification factor. |
| Normalization Rates of ALP at Week 12 in the Double-Blind Treatment Period | Week 12 | Percentage of participants achieving a response in serum ALP at Week 12 was assessed using non-responder imputation. Analyses of ALP response rates and normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor. |
| Normalization Rates of Biochemical Disease Markers in the Double-Blind Treatment Period | Week 12 | Percentage of participants achieving a response in biochemical disease markers including Alanine Aminotransferase (ALT), Gamma-Glutamyl Transpeptidase (GGT), Aspartate Aminotransferase (AST), Total and conjugated Bilirubin and lipid panel (cholesterol, high density lipoprotein \[HDL\] and low-density lipoprotein \[LDL\]) at Week 12 has been presented. Analyses of response rates and normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor. |
| Change From Baseline in GGT, ALT and AST Levels in the Double-Blind Treatment Period | Baseline and at Week 12 | Blood samples were collected at indicated timepoint and change from Baseline in GGT, ALT and AST were analyzed using the MMRM model and results were summarized in standard International System of Units (SI) by treatment group using descriptive statistics at baseline and at each on-study evaluation. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from baseline was calculated as post baseline value minus baseline value. |
| Change From Baseline in Total and Conjugated Bilirubin in the Double-Blind Treatment Period | Baseline and at Week 12 | Blood samples were collected at indicated timepoints and the changes in total and conjugated bilirubin were evaluated using MMRM to assess the effects of treatment groups over time. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from baseline was calculated as post baseline value minus baseline value. |
| Change From Baseline in Lipid Panel in the Double-Blind Treatment Period | Baseline and at Week 12 | Blood samples were collected at indicated timepoints and the changes in lipid panel including cholesterol, HDL and LDL were evaluated using MMRM to assess the effects of treatment groups over time. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product in the DB period. Change from Baseline was calculated as post Baseline value minus Baseline value. |
| Change From Baseline in 7 Alpha (α) Hydroxy 4 Cholesten-3 One (C4) in the Double-Blind Treatment Period | Baseline and at Week 12 | Blood samples were collected at indicated timepoints for the assessment of C4. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product. Change from Baseline was calculated as change equals post baseline value minus baseline value. |
| Change From Baseline in Bile Acid in the Double-Blind Treatment Period | Baseline and at Week 12 | Blood samples were collected for the assessment of bile acids. Baseline was defined as the mean of all available evaluations prior to the first administration of investigational product. Change from Baseline was calculated as change equals post Baseline value minus Baseline value. |
Countries
Australia, Belgium, Croatia, Czechia, Estonia, France, Germany, Greece, Hungary, Israel, Lithuania, Netherlands, Norway, Poland, South Korea, Spain, United Kingdom
Contacts
STUDY_DIRECTORLynda Szczech
Intercept Pharmaceuticals, Inc.
Participant flow
Recruitment details
This was a Phase 2, Proof -of-concept, randomized, double-blind (DB), parallel-group study that evaluated the efficacy, safety, and tolerability of obeticholic acid (OCA) administered in combination with 2 different Bezafibrate (BZF) doses or BZF alone participants with primary biliary cholangitis (PBC) for up to 12 weeks.
Pre-assignment details
A total of 75 participants were enrolled. Two participants in the DB period discontinued study treatment during the DB period but remained in the study until its completion for safety follow-up. As they were no longer receiving the investigational product, they did not proceed into the LTSE period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 67 Participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 | 0 / 19 | 0 / 18 | 0 / 64 |
| other Total, other adverse events | 15 / 19 | 15 / 19 | 16 / 19 | 14 / 18 | 47 / 64 |
| serious Total, serious adverse events | 2 / 19 | 1 / 19 | 3 / 19 | 2 / 18 | 1 / 64 |
Outcome results
None listed