Primary Biliary Cholangitis
Conditions
Keywords
Primary Biliary Cholangitis, Primary Biliary Cirrhosis, Hepatic Impairment, Cirrhosis, Liver
Brief summary
Study to determine the effect of the investigational drug bezafibrate (BZF) alone and in combination with the investigational drug obeticholic acid (OCA) in participants with Primary Biliary Cholangitis (PBC).
Interventions
DRUGBezafibrate 100 mg
One tablet of bezafibrate 100 mg IR once daily
Two tablets of bezafibrate 200 mg IR once daily for BZF 400 mg IR
One tablet of obeticholic acid 5 mg tablet once daily.
One tablet of obeticholic acid placebo tablet once daily
DRUGBezafibrate Placebo
One tablet of bezafibrate placebo tablet once daily
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 * Presence of clinical complications of PBC * History or presence of 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 participation in a previous study involving OCA, or other farnesoid X receptor (FXR) agonists, or peroxisome proliferator activated receptor (PPAR)-agonists within 3 months before Screening * Unable to tolerate BZF or other fibrates, treatment with commercially available fibrates, or participation in a previous study involving fibrate within 3 months before Screening. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Alkaline Phosphatase (ALP) | Baseline to Week 12 | Serum samples were collected at scheduled visits during the double-blind treatment period. Changes in ALP were evaluated using a mixed-effects repeated-measures model (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. 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 | At Week 12 | Responders were defined as participants achieving a ≥10%, ≥20%, ≥30%, or ≥40% reduction from baseline in serum ALP at week 12 during the DB treatment period with non-responder imputation applied. Baseline ALP was defined as the last evaluations prior to the first administration of investigational product. 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 | At Week 12 | Percentage of participants achieving a response in serum ALP at week 12 during the DB treatment period was assessed using non-responder imputation. Analyses of ALP normalization rates were performed using a Cochran-Mantel-Haenszel test stratified by the randomization stratification factor. |
| Normalization Rates of Biochemical Disease Markers | At Week 12 | Percentage of participants achieving a response in biochemical disease markers including ALP, alanine amino transferase (ALT), aspartate amino transferase (AST), gamma-glutamyl transferase (GGT), total and conjugated bilirubin and lipid panel (cholesterol, high density lipoprotein \[HDL\] and low density lipoprotein \[LDL\]) at Week 12 during the DB treatment period 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 in GGT, ALT and AST Levels | 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. Change from baseline was calculated as post Baseline value minus Baseline value. |
| Change From Baseline in Total and Conjugated Bilirubin | 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. Change from baseline was calculated as post Baseline value minus Baseline value. |
| Change From Baseline in Lipid Panel | 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. Change from baseline was calculated as post Baseline value minus Baseline value. |
| Change From Baseline of the Plasma Value of 7 Alpha (α) Hydroxy 4 Cholesten-3 One (C4) | 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 post Baseline value minus Baseline value. |
| Number of Participants With Clinically Significant Changes From Baseline in Bile Acids | 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. |
Countries
Argentina, Canada, Italy, United States
Contacts
STUDY_DIRECTORLynda Szczech, M.D.
Intercept Pharmaceuticals, Inc
Participant flow
Recruitment details
This was a Phase 2a, double-blind (DB), randomized, active-controlled, parallel group study to evaluate the efficacy, safety and tolerability of Obeticholic Acid (OCA) administered in combination with Bezafibrate (BZF) doses compared to BZF alone in participants with Primary Biliary Cholangitis (PBC). The eligible participants from double-blind phase entered the Long-Term Safety Extension (LTSE) phase.
Pre-assignment details
A total of 72 participants were enrolled into the double-blind phase of the study. 67 participants entered the LTSE phase.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 10.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 70 Participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 1 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 / 16 | 0 / 19 | 0 / 18 | 0 / 67 |
| other Total, other adverse events | 13 / 19 | 9 / 16 | 16 / 19 | 14 / 18 | 59 / 67 |
| serious Total, serious adverse events | 0 / 19 | 0 / 16 | 3 / 19 | 0 / 18 | 4 / 67 |
Outcome results
None listed