Trial Outcomes & Findings for Study of INT 747 in Combination With URSO in Patients With Primay Biliary Cirrhosis (PBC) (NCT NCT00550862)
NCT ID: NCT00550862
Last Updated: 2024-02-06
Results Overview
Blood samples were collected for the analysis of serum ALP. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
165 participants
Primary outcome timeframe
Baseline and Up to Day 85
Results posted on
2024-02-06
Participant Flow
This was an international, multi-center, randomized, double-blind, placebo-controlled, multi-dose study with the majority of the sites being academic centers.
A total of 165 participants were enrolled into the double-blind phase of the study. Of these, 78 participants (21 of whom had received placebo) entered the open-label long-term safety extension (LTSE) phase
Participant milestones
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
LTSE OCA Total
A total of 78 participants from the double-blind phase entered the open-label LTSE phase of the study. Seven participants entered the LTSE within 2 weeks of completing the double-blind phase. Participants initially started dosing at less than or equal to (\<=) 10 mg daily OCA and doses up to 50 mg daily were evaluated. Entry of 71 participants from double-blind phase to LTSE phase was delayed up to 10 months due to administrative reasons. All participants received open-label OCA during the LTSE phase of the study. Eligible participant who completed the DB phase were enrolled into the LTSE phase.
|
|---|---|---|---|---|---|
|
Double-Blind Phase (Day 1 to Day 85)
STARTED
|
38
|
48
|
41
|
38
|
0
|
|
Double-Blind Phase (Day 1 to Day 85)
COMPLETED
|
32
|
42
|
25
|
37
|
0
|
|
Double-Blind Phase (Day 1 to Day 85)
NOT COMPLETED
|
6
|
6
|
16
|
1
|
0
|
|
LTSE Phase (Up to 12 Months)
STARTED
|
0
|
0
|
0
|
0
|
78
|
|
LTSE Phase (Up to 12 Months)
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
LTSE Phase (Up to 12 Months)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
78
|
Reasons for withdrawal
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
LTSE OCA Total
A total of 78 participants from the double-blind phase entered the open-label LTSE phase of the study. Seven participants entered the LTSE within 2 weeks of completing the double-blind phase. Participants initially started dosing at less than or equal to (\<=) 10 mg daily OCA and doses up to 50 mg daily were evaluated. Entry of 71 participants from double-blind phase to LTSE phase was delayed up to 10 months due to administrative reasons. All participants received open-label OCA during the LTSE phase of the study. Eligible participant who completed the DB phase were enrolled into the LTSE phase.
|
|---|---|---|---|---|---|
|
Double-Blind Phase (Day 1 to Day 85)
Adverse Event
|
5
|
5
|
12
|
1
|
0
|
|
Double-Blind Phase (Day 1 to Day 85)
Elevated conjugated (direct) bilirubin
|
1
|
0
|
2
|
0
|
0
|
|
Double-Blind Phase (Day 1 to Day 85)
Elevated aspartate transaminase (AST)/ alanine transaminase (ALT) levels
|
0
|
0
|
1
|
0
|
0
|
|
Double-Blind Phase (Day 1 to Day 85)
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
0
|
|
Double-Blind Phase (Day 1 to Day 85)
Lost to Follow-up
|
0
|
1
|
0
|
0
|
0
|
|
LTSE Phase (Up to 12 Months)
Adverse Event
|
0
|
0
|
0
|
0
|
14
|
|
LTSE Phase (Up to 12 Months)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
2
|
|
LTSE Phase (Up to 12 Months)
Protocol Violation
|
0
|
0
|
0
|
0
|
1
|
|
LTSE Phase (Up to 12 Months)
Other
|
0
|
0
|
0
|
0
|
2
|
|
LTSE Phase (Up to 12 Months)
Other: Study stopped by sponsor due to administrative reasons
|
0
|
0
|
0
|
0
|
59
|
Baseline Characteristics
Study of INT 747 in Combination With URSO in Patients With Primay Biliary Cirrhosis (PBC)
Baseline characteristics by cohort
| Measure |
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Total
n=165 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
55.9 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
54.0 years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
55.6 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
54.8 years
STANDARD_DEVIATION 8.5 • n=4 Participants
|
55.1 years
STANDARD_DEVIATION 8.8 • n=21 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
38 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
157 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
47 participants
n=7 Participants
|
40 participants
n=5 Participants
|
37 participants
n=5 Participants
|
34 participants
n=4 Participants
|
158 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Region of Enrollment
France
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=7 Participants
|
19 participants
n=5 Participants
|
15 participants
n=5 Participants
|
17 participants
n=4 Participants
|
72 participants
n=21 Participants
|
|
Region of Enrollment
Canada
|
15 participants
n=7 Participants
|
14 participants
n=5 Participants
|
13 participants
n=5 Participants
|
13 participants
n=4 Participants
|
55 participants
n=21 Participants
|
|
Region of Enrollment
Spain
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Region of Enrollment
Austria
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Region of Enrollment
Germany
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
8 participants
n=21 Participants
|
|
Region of Enrollment
Netherlands
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
4 participants
n=21 Participants
|
|
Region of Enrollment
United Kingdom
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
4 participants
n=5 Participants
|
3 participants
n=4 Participants
|
12 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and Up to Day 85Population: Modified Intent-to-Treat (mITT) Population (N=161) comprised of all randomized participants who received at least 1 dose of investigational product and had at least 1 post-Baseline ALP evaluation taken ≤7 days after their last dose of investigational product.
Blood samples were collected for the analysis of serum ALP. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=47 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=39 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=37 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP)
|
-23.7 Percent change
Standard Deviation 17.8
|
-24.7 Percent change
Standard Deviation 17.9
|
-21.0 Percent change
Standard Deviation 27.6
|
-2.6 Percent change
Standard Deviation 12.5
|
SECONDARY outcome
Timeframe: Baseline and at Days 15, 29, 57 and 85Population: Intent-to-Treat (ITT) Population (N=165) comprises all randomized participants who received at least 1 dose of investigational product. Only those participants with data available at specified timepoints has been presented.
Blood samples were collected for the analysis of serum chemistry parameters including ALP, AST, ALT and GGT. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALP, Baseline
|
294.4 Units per liter
Standard Deviation 149.4
|
290.0 Units per liter
Standard Deviation 123.6
|
289.5 Units per liter
Standard Deviation 106.2
|
275.2 Units per liter
Standard Deviation 102.7
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALP, Day 15
|
247.6 Units per liter
Standard Deviation 117.9
|
239.3 Units per liter
Standard Deviation 113.6
|
231.2 Units per liter
Standard Deviation 87.5
|
269.2 Units per liter
Standard Deviation 105.6
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALP, Day 29
|
227.2 Units per liter
Standard Deviation 105.0
|
219.2 Units per liter
Standard Deviation 100.5
|
216.1 Units per liter
Standard Deviation 90.5
|
266.1 Units per liter
Standard Deviation 118.0
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALP, Day 57
|
212.6 Units per liter
Standard Deviation 98.9
|
231.7 Units per liter
Standard Deviation 177.6
|
189.2 Units per liter
Standard Deviation 67.5
|
271.5 Units per liter
Standard Deviation 123.0
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALP, Day 85
|
219.0 Units per liter
Standard Deviation 113.5
|
225.0 Units per liter
Standard Deviation 169.1
|
227.9 Units per liter
Standard Deviation 115.9
|
270.7 Units per liter
Standard Deviation 118.7
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
AST, Baseline
|
49 Units per liter
Standard Deviation 22
|
44 Units per liter
Standard Deviation 23
|
48 Units per liter
Standard Deviation 24
|
42 Units per liter
Standard Deviation 19
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
AST, Day 15
|
44 Units per liter
Standard Deviation 23
|
38 Units per liter
Standard Deviation 19
|
47 Units per liter
Standard Deviation 34
|
41 Units per liter
Standard Deviation 17
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
AST, Day 29
|
37 Units per liter
Standard Deviation 13
|
36 Units per liter
Standard Deviation 19
|
43 Units per liter
Standard Deviation 28
|
42 Units per liter
Standard Deviation 20
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
AST, Day 57
|
36 Units per liter
Standard Deviation 14
|
40 Units per liter
Standard Deviation 45
|
37 Units per liter
Standard Deviation 17
|
45 Units per liter
Standard Deviation 28
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
AST, Day 85
|
40 Units per liter
Standard Deviation 23
|
37 Units per liter
Standard Deviation 25
|
41 Units per liter
Standard Deviation 24
|
41 Units per liter
Standard Deviation 17
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALT, Baseline
|
51 Units per liter
Standard Deviation 29
|
51 Units per liter
Standard Deviation 36
|
53 Units per liter
Standard Deviation 35
|
47 Units per liter
Standard Deviation 26
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALT, Day 15
|
40 Units per liter
Standard Deviation 20
|
37 Units per liter
Standard Deviation 28
|
49 Units per liter
Standard Deviation 49
|
48 Units per liter
Standard Deviation 24
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALT, Day 29
|
35 Units per liter
Standard Deviation 15
|
32 Units per liter
Standard Deviation 25
|
43 Units per liter
Standard Deviation 40
|
46 Units per liter
Standard Deviation 25
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALT, Day 57
|
32 Units per liter
Standard Deviation 16
|
39 Units per liter
Standard Deviation 70
|
34 Units per liter
Standard Deviation 23
|
49 Units per liter
Standard Deviation 29
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
ALT, Day 85
|
34 Units per liter
Standard Deviation 20
|
34 Units per liter
Standard Deviation 38
|
39 Units per liter
Standard Deviation 32
|
45 Units per liter
Standard Deviation 24
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
GGT, Baseline
|
228 Units per liter
Standard Deviation 212
|
273 Units per liter
Standard Deviation 267
|
231 Units per liter
Standard Deviation 182
|
189 Units per liter
Standard Deviation 139
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
GGT, Day 15
|
137 Units per liter
Standard Deviation 119
|
155 Units per liter
Standard Deviation 197
|
108 Units per liter
Standard Deviation 88
|
190 Units per liter
Standard Deviation 141
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
GGT, Day 29
|
108 Units per liter
Standard Deviation 92
|
109 Units per liter
Standard Deviation 153
|
93 Units per liter
Standard Deviation 90
|
196 Units per liter
Standard Deviation 158
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
GGT, Day 57
|
96 Units per liter
Standard Deviation 91
|
104 Units per liter
Standard Deviation 189
|
76 Units per liter
Standard Deviation 86
|
195 Units per liter
Standard Deviation 165
|
|
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
GGT, Day 85
|
107 Units per liter
Standard Deviation 124
|
115 Units per liter
Standard Deviation 178
|
95 Units per liter
Standard Deviation 89
|
209 Units per liter
Standard Deviation 170
|
SECONDARY outcome
Timeframe: Baseline and at Days 15, 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=164).
Blood samples were collected for the analysis of serum chemistry parameters including ALP, AST, ALT and GGT. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=40 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, Day 15
|
-13.5 Percent change
Standard Deviation 12.8
|
-17.3 Percent change
Standard Deviation 9.8
|
-16.1 Percent change
Standard Deviation 21.9
|
-2.6 Percent change
Standard Deviation 10.8
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, Day 29
|
-20.8 Percent change
Standard Deviation 14.2
|
-23.4 Percent change
Standard Deviation 12.3
|
-25.0 Percent change
Standard Deviation 17.5
|
-4.6 Percent change
Standard Deviation 12.4
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, Day 57
|
-26.0 Percent change
Standard Deviation 15.4
|
-22.0 Percent change
Standard Deviation 17.2
|
-29.0 Percent change
Standard Deviation 18.6
|
-0.9 Percent change
Standard Deviation 17.1
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, Day 85
|
-23.3 Percent change
Standard Deviation 17.1
|
-24.0 Percent change
Standard Deviation 18.8
|
-20.0 Percent change
Standard Deviation 27.4
|
-2.6 Percent change
Standard Deviation 12.4
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, Day 15
|
-6 Percent change
Standard Deviation 42
|
-14 Percent change
Standard Deviation 18
|
13 Percent change
Standard Deviation 119
|
3 Percent change
Standard Deviation 23
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, Day 29
|
-16 Percent change
Standard Deviation 22
|
-17 Percent change
Standard Deviation 18
|
-13 Percent change
Standard Deviation 26
|
2 Percent change
Standard Deviation 27
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, Day 57
|
-19 Percent change
Standard Deviation 22
|
-13 Percent change
Standard Deviation 30
|
-15 Percent change
Standard Deviation 27
|
20 Percent change
Standard Deviation 95
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, Day 85
|
-17 Percent change
Standard Deviation 21
|
-16 Percent change
Standard Deviation 20
|
-9 Percent change
Standard Deviation 38
|
-0 Percent change
Standard Deviation 23
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, Day 15
|
-11 Percent change
Standard Deviation 61
|
-26 Percent change
Standard Deviation 18
|
12 Percent change
Standard Deviation 176
|
6 Percent change
Standard Deviation 30
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, Day 29
|
-25 Percent change
Standard Deviation 28
|
-33 Percent change
Standard Deviation 18
|
-29 Percent change
Standard Deviation 27
|
1 Percent change
Standard Deviation 31
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, Day 57
|
-31 Percent change
Standard Deviation 23
|
-32 Percent change
Standard Deviation 33
|
-35 Percent change
Standard Deviation 24
|
8 Percent change
Standard Deviation 43
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, Day 85
|
-28 Percent change
Standard Deviation 27
|
-35 Percent change
Standard Deviation 22
|
-21 Percent change
Standard Deviation 49
|
-0 Percent change
Standard Deviation 35
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, Day 15
|
-35 Percent change
Standard Deviation 14
|
-43 Percent change
Standard Deviation 14
|
-49 Percent change
Standard Deviation 12
|
-1 Percent change
Standard Deviation 15
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, Day 29
|
-48 Percent change
Standard Deviation 19
|
-61 Percent change
Standard Deviation 15
|
-63 Percent change
Standard Deviation 16
|
1 Percent change
Standard Deviation 24
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, Day 57
|
-53 Percent change
Standard Deviation 26
|
-64 Percent change
Standard Deviation 24
|
-67 Percent change
Standard Deviation 18
|
2 Percent change
Standard Deviation 20
|
|
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, Day 85
|
-48 Percent change
Standard Deviation 30
|
-63 Percent change
Standard Deviation 24
|
-57 Percent change
Standard Deviation 31
|
7 Percent change
Standard Deviation 28
|
SECONDARY outcome
Timeframe: Baseline and at 3, 6, 9 and 12 MonthsPopulation: Safety Population (N=78) comprised of all randomized participants who received at least 1 dose of investigational product. Only those participants with data available at specified timepoints has been presented (n=69).
Blood samples were collected for the analysis of serum chemistry parameters including ALP, AST, ALT and GGT. Baseline was defined as the last observed value before the first dose of investigational product (Day 85). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=69 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, 3-Month
|
-22.2 Percent change
Standard Deviation 18.2
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, 6-Month
|
-23.7 Percent change
Standard Deviation 22.7
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, 9-Month
|
-25.3 Percent change
Standard Deviation 22.2
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALP, 12-Month
|
-26.5 Percent change
Standard Deviation 22.0
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, 3-Month
|
2.3 Percent change
Standard Deviation 29.2
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, 6-Month
|
-1.2 Percent change
Standard Deviation 26.6
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, 9-Month
|
-4.7 Percent change
Standard Deviation 27.1
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
AST, 12-Month
|
-0.7 Percent change
Standard Deviation 27.1
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, 3-Month
|
-17.8 Percent change
Standard Deviation 28.5
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, 6-Month
|
-22.9 Percent change
Standard Deviation 26.5
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, 9-Month
|
-23.3 Percent change
Standard Deviation 40.7
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
ALT, 12-Month
|
-20.7 Percent change
Standard Deviation 26.4
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, 3-Month
|
-52.4 Percent change
Standard Deviation 25.4
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, 6-Month
|
-57.5 Percent change
Standard Deviation 33.3
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, 9-Month
|
-60.9 Percent change
Standard Deviation 24.9
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
GGT, 12-Month
|
-60.4 Percent change
Standard Deviation 25.5
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and at Days 15, 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented.
Blood samples were collected for the analysis of serum chemistry parameter: Albumin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Albumin Levels
Day 85
|
39.95 Grams per liter
Standard Deviation 4.19
|
41.09 Grams per liter
Standard Deviation 4.01
|
41.24 Grams per liter
Standard Deviation 3.86
|
41.69 Grams per liter
Standard Deviation 4.05
|
|
Double-blind Phase: Absolute Values for Albumin Levels
Baseline
|
40.14 Grams per liter
Standard Deviation 4.66
|
41.17 Grams per liter
Standard Deviation 3.85
|
42.41 Grams per liter
Standard Deviation 2.77
|
42.03 Grams per liter
Standard Deviation 3.23
|
|
Double-blind Phase: Absolute Values for Albumin Levels
Day 15
|
39.84 Grams per liter
Standard Deviation 4.33
|
41.12 Grams per liter
Standard Deviation 3.59
|
41.15 Grams per liter
Standard Deviation 3.05
|
41.84 Grams per liter
Standard Deviation 3.38
|
|
Double-blind Phase: Absolute Values for Albumin Levels
Day 29
|
40.01 Grams per liter
Standard Deviation 3.38
|
40.94 Grams per liter
Standard Deviation 3.74
|
41.05 Grams per liter
Standard Deviation 3.64
|
41.21 Grams per liter
Standard Deviation 3.50
|
|
Double-blind Phase: Absolute Values for Albumin Levels
Day 57
|
40.29 Grams per liter
Standard Deviation 3.65
|
41.04 Grams per liter
Standard Deviation 3.90
|
41.76 Grams per liter
Standard Deviation 3.00
|
40.50 Grams per liter
Standard Deviation 4.33
|
SECONDARY outcome
Timeframe: Baseline and at Days 15, 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented.
Blood samples were collected for the analysis of serum chemistry parameter: Albumin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Percent Change From Baseline in Albumin Levels
Day 15
|
-0.42 Percent change
Standard Deviation 5.68
|
-0.29 Percent change
Standard Deviation 5.71
|
-2.66 Percent change
Standard Deviation 4.70
|
-0.41 Percent change
Standard Deviation 5.18
|
|
Double-blind Phase: Percent Change From Baseline in Albumin Levels
Day 29
|
-1.62 Percent change
Standard Deviation 4.52
|
-0.73 Percent change
Standard Deviation 5.10
|
-2.59 Percent change
Standard Deviation 5.69
|
-1.97 Percent change
Standard Deviation 4.78
|
|
Double-blind Phase: Percent Change From Baseline in Albumin Levels
Day 57
|
-0.69 Percent change
Standard Deviation 5.56
|
-0.26 Percent change
Standard Deviation 4.83
|
-2.00 Percent change
Standard Deviation 4.27
|
-3.58 Percent change
Standard Deviation 6.90
|
|
Double-blind Phase: Percent Change From Baseline in Albumin Levels
Day 85
|
-0.13 Percent change
Standard Deviation 5.03
|
-0.11 Percent change
Standard Deviation 5.42
|
-2.82 Percent change
Standard Deviation 6.04
|
-0.82 Percent change
Standard Deviation 5.79
|
SECONDARY outcome
Timeframe: Baseline and at Days 15, 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented.
Blood samples were collected for the analysis of serum chemistry parameter: Conjugated (Direct) bilirubin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Baseline
|
4.2 Micromoles per liter
Standard Deviation 3.1
|
3.9 Micromoles per liter
Standard Deviation 2.4
|
4.7 Micromoles per liter
Standard Deviation 3.3
|
3.6 Micromoles per liter
Standard Deviation 2.8
|
|
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Day 15
|
4.9 Micromoles per liter
Standard Deviation 5.0
|
3.1 Micromoles per liter
Standard Deviation 2.2
|
3.3 Micromoles per liter
Standard Deviation 2.2
|
3.4 Micromoles per liter
Standard Deviation 2.4
|
|
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Day 29
|
3.3 Micromoles per liter
Standard Deviation 2.6
|
3.3 Micromoles per liter
Standard Deviation 2.6
|
5.6 Micromoles per liter
Standard Deviation 14.4
|
3.7 Micromoles per liter
Standard Deviation 2.8
|
|
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Day 57
|
3.4 Micromoles per liter
Standard Deviation 3.1
|
3.4 Micromoles per liter
Standard Deviation 2.6
|
3.0 Micromoles per liter
Standard Deviation 1.6
|
3.5 Micromoles per liter
Standard Deviation 3.0
|
|
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Day 85
|
3.9 Micromoles per liter
Standard Deviation 3.8
|
3.2 Micromoles per liter
Standard Deviation 2.7
|
5.5 Micromoles per liter
Standard Deviation 8.5
|
3.6 Micromoles per liter
Standard Deviation 3.2
|
SECONDARY outcome
Timeframe: Baseline and at Days 15, 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=164).
Blood samples were collected for the analysis of serum chemistry parameter: Direct bilirubin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=40 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
Day 85
|
0.0 Percent change
Standard Deviation 49.6
|
-12.2 Percent change
Standard Deviation 40.0
|
10.0 Percent change
Standard Deviation 143.2
|
3.7 Percent change
Standard Deviation 48.2
|
|
Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
Day 15
|
14.6 Percent change
Standard Deviation 60.9
|
-15.3 Percent change
Standard Deviation 38.1
|
-17.6 Percent change
Standard Deviation 35.4
|
2.7 Percent change
Standard Deviation 38.2
|
|
Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
Day 29
|
-3.3 Percent change
Standard Deviation 41.2
|
-11.8 Percent change
Standard Deviation 43.7
|
31.3 Percent change
Standard Deviation 276.8
|
12.2 Percent change
Standard Deviation 39.3
|
|
Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
Day 57
|
-2.9 Percent change
Standard Deviation 39.6
|
-8.8 Percent change
Standard Deviation 44.1
|
-18.7 Percent change
Standard Deviation 31.3
|
1.4 Percent change
Standard Deviation 32.8
|
SECONDARY outcome
Timeframe: Baseline and at 3, 6, 9 and 12 MonthsPopulation: Safety Population (N=78). Only those participants with data available at specified timepoints has been presented (n=69)
Blood samples were collected for the analysis of serum chemistry parameters Total and direct bilirubin. Baseline was defined as the last observed value before the first dose of investigational product (Day 85). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=69 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Direct bilirubin, 3-Month
|
19.6 Percent change
Standard Deviation 46.2
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Direct bilirubin, 6-Month
|
24.6 Percent change
Standard Deviation 53.2
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Direct bilirubin, 9-Month
|
15.2 Percent change
Standard Deviation 44.3
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Total bilirubin, 3-Month
|
-17.0 Percent change
Standard Deviation 28.0
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Total bilirubin, 6-Month
|
-11.6 Percent change
Standard Deviation 25.2
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Total bilirubin, 9-Month
|
-18.3 Percent change
Standard Deviation 29.7
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Total bilirubin, 12-Month
|
-8.9 Percent change
Standard Deviation 35.8
|
—
|
—
|
—
|
|
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Direct bilirubin, 12-Month
|
23.1 Percent change
Standard Deviation 68.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=146).
Enhanced Liver Fibrosis (ELF) combines measurements of tissue inhibitor of metalloprotein-ases-1 (TIMP-1), amino-terminal pro-peptide of type III procollagen (PIIINP), and hyaluronic acid (HA). The ELF score is calculated as: 2.278 + 0.851 ln (HA) + 0.751 ln (PIIINP) + 0.394 ln (TIMP-1). An ELF score of less than 7.7 indicates no to mild fibrosis; ≥ 7.7 - \< 9.8: Moderate fibrosis; ≥ 9.8 - \< 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis. Higher the ELF is associated with higher fibrosis stages and greater the risk of progression. A minimum and maximum value for the scale range does not exist for this assessment. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=32 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=42 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=36 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=36 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score
|
-0.095 Scores on a scale
Standard Deviation 0.593
|
0.008 Scores on a scale
Standard Deviation 0.561
|
0.124 Scores on a scale
Standard Deviation 0.685
|
-0.212 Scores on a scale
Standard Deviation 0.627
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=146).
Blood samples were collected for the analysis of extracellular matrix markers, including TIMP-1, PIIINP, and HA. The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=32 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=42 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=36 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=36 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels
HA
|
-6.771 Nanograms per milliliter
Standard Deviation 59.677
|
12.287 Nanograms per milliliter
Standard Deviation 73.090
|
20.117 Nanograms per milliliter
Standard Deviation 97.056
|
-21.359 Nanograms per milliliter
Standard Deviation 69.389
|
|
Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels
P3NP
|
-0.503 Nanograms per milliliter
Standard Deviation 3.017
|
-0.468 Nanograms per milliliter
Standard Deviation 2.389
|
1.858 Nanograms per milliliter
Standard Deviation 6.547
|
-0.943 Nanograms per milliliter
Standard Deviation 3.206
|
|
Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels
TIMP-1
|
15.341 Nanograms per milliliter
Standard Deviation 218.71
|
-18.409 Nanograms per milliliter
Standard Deviation 191.768
|
43.921 Nanograms per milliliter
Standard Deviation 222.930
|
-65.196 Nanograms per milliliter
Standard Deviation 257.295
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n-144).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including C-reactive protein. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=36 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=35 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=32 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
Baseline
|
7.9 Milligrams per milliliter
Standard Deviation 7.5
|
7.8 Milligrams per milliliter
Standard Deviation 8.9
|
5.2 Milligrams per milliliter
Standard Deviation 5.6
|
5.1 Milligrams per milliliter
Standard Deviation 4.6
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
Day 85
|
6.4 Milligrams per milliliter
Standard Deviation 7.2
|
4.0 Milligrams per milliliter
Standard Deviation 4.4
|
6.0 Milligrams per milliliter
Standard Deviation 13.2
|
6.0 Milligrams per milliliter
Standard Deviation 5.8
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=114).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including C-reactive protein. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=28 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=31 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=27 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=28 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
|
-1.8 Milligrams per milliliter
Standard Deviation 7.9
|
-3.7 Milligrams per milliliter
Standard Deviation 6.6
|
1.4 Milligrams per milliliter
Standard Deviation 9.4
|
0.3 Milligrams per milliliter
Standard Deviation 3.7
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=143).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including NEFA. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=35 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=35 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=32 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA)
Baseline
|
0.58 Millimoles per liter
Standard Deviation 0.23
|
0.55 Millimoles per liter
Standard Deviation 0.24
|
0.62 Millimoles per liter
Standard Deviation 0.23
|
0.54 Millimoles per liter
Standard Deviation 0.26
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA)
Day 85
|
0.49 Millimoles per liter
Standard Deviation 0.24
|
0.51 Millimoles per liter
Standard Deviation 0.19
|
0.55 Millimoles per liter
Standard Deviation 0.25
|
0.56 Millimoles per liter
Standard Deviation 0.19
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=112).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including NEFA. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=27 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=30 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=27 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=28 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA
|
-0.06 Millimoles per liter
Standard Deviation 0.19
|
-0.01 Millimoles per liter
Standard Deviation 0.27
|
-0.07 Millimoles per liter
Standard Deviation 0.20
|
0.04 Millimoles per liter
Standard Deviation 0.25
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=144).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-alpha. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=35 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=35 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=33 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha)
Baseline
|
15.6 Nanograms per liter
Standard Deviation 7.1
|
13.8 Nanograms per liter
Standard Deviation 4.4
|
16.1 Nanograms per liter
Standard Deviation 11.7
|
11.4 Nanograms per liter
Standard Deviation 3.2
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha)
Day 85
|
18.1 Nanograms per liter
Standard Deviation 14.8
|
15.4 Nanograms per liter
Standard Deviation 7.3
|
16.2 Nanograms per liter
Standard Deviation 12.1
|
13.6 Nanograms per liter
Standard Deviation 4.5
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=119).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-alpha. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=28 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=33 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=28 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=30 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha
|
3.0 Nanograms per liter
Standard Deviation 15.6
|
1.7 Nanograms per liter
Standard Deviation 5.7
|
-0.2 Nanograms per liter
Standard Deviation 15.8
|
1.2 Nanograms per liter
Standard Deviation 4.2
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N-165). Only those participants with data available at specified timepoints has been presented (142).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-beta and TGF-beta. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=31 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=43 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=34 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=34 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
TNF-beta, Baseline
|
13.1 Picomoles per liter
Standard Deviation 14.8
|
10.8 Picomoles per liter
Standard Deviation 12.2
|
8.7 Picomoles per liter
Standard Deviation 10.4
|
8.8 Picomoles per liter
Standard Deviation 12.0
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
TNF-beta, Day 85
|
11.0 Picomoles per liter
Standard Deviation 7.8
|
14.5 Picomoles per liter
Standard Deviation 17.0
|
6.7 Picomoles per liter
Standard Deviation 7.6
|
10.9 Picomoles per liter
Standard Deviation 17.3
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
TGF-beta, Baseline
|
35.6 Picomoles per liter
Standard Deviation 22.0
|
37.0 Picomoles per liter
Standard Deviation 23.3
|
26.2 Picomoles per liter
Standard Deviation 22.9
|
36.4 Picomoles per liter
Standard Deviation 25.3
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
TGF-beta, Day 85
|
39.2 Picomoles per liter
Standard Deviation 22.9
|
41.0 Picomoles per liter
Standard Deviation 25.7
|
40.4 Picomoles per liter
Standard Deviation 22.3
|
30.1 Picomoles per liter
Standard Deviation 23.1
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=120).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-beta and TGF-beta. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=26 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=35 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=31 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=28 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta
TNF-beta
|
-11.3 Picomoles per liter
Standard Deviation 25.1
|
3.9 Picomoles per liter
Standard Deviation 6.1
|
2.2 Picomoles per liter
Standard Deviation 7.1
|
1.1 Picomoles per liter
Standard Deviation 11.2
|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta
TGF-beta
|
3.7 Picomoles per liter
Standard Deviation 22.1
|
3.4 Picomoles per liter
Standard Deviation 27.9
|
14.0 Picomoles per liter
Standard Deviation 27.8
|
0.1 Picomoles per liter
Standard Deviation 30.0
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=144).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Bile acids and glutathion. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=35 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=35 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=33 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Bile acids, Baseline
|
36.9 Micromoles per liter
Standard Deviation 31.7
|
29.5 Micromoles per liter
Standard Deviation 26.1
|
36.0 Micromoles per liter
Standard Deviation 48.9
|
27.6 Micromoles per liter
Standard Deviation 32.3
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Bile acids, Day 85
|
37.8 Micromoles per liter
Standard Deviation 47.3
|
30.2 Micromoles per liter
Standard Deviation 42.9
|
34.6 Micromoles per liter
Standard Deviation 57.2
|
26.2 Micromoles per liter
Standard Deviation 29.2
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Glutathione, Baseline
|
3.7 Micromoles per liter
Standard Deviation 1.3
|
4.0 Micromoles per liter
Standard Deviation 1.9
|
3.4 Micromoles per liter
Standard Deviation 1.6
|
3.8 Micromoles per liter
Standard Deviation 1.8
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Glutathione, Day 85
|
5.0 Micromoles per liter
Standard Deviation 2.1
|
5.3 Micromoles per liter
Standard Deviation 1.9
|
4.8 Micromoles per liter
Standard Deviation 2.0
|
4.8 Micromoles per liter
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=119).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Bile acids and glutathion. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=28 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=33 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=28 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=30 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Bile acids
|
-1.4 Micromoles per liter
Standard Deviation 38.7
|
-1.1 Micromoles per liter
Standard Deviation 36.3
|
0.5 Micromoles per liter
Standard Deviation 77.9
|
-1.0 Micromoles per liter
Standard Deviation 28.3
|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Glutathione
|
1.4 Micromoles per liter
Standard Deviation 1.7
|
1.3 Micromoles per liter
Standard Deviation 1.9
|
1.2 Micromoles per liter
Standard Deviation 1.4
|
1.0 Micromoles per liter
Standard Deviation 2.3
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=144).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including IgM. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=35 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=35 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=33 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM)
Baseline
|
4.31 Grams per liter
Standard Deviation 2.12
|
3.13 Grams per liter
Standard Deviation 1.95
|
3.82 Grams per liter
Standard Deviation 3.35
|
3.06 Grams per liter
Standard Deviation 1.73
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM)
Day 85
|
3.73 Grams per liter
Standard Deviation 1.91
|
2.62 Grams per liter
Standard Deviation 1.76
|
3.02 Grams per liter
Standard Deviation 2.14
|
2.97 Grams per liter
Standard Deviation 1.61
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=119).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including IgM. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=28 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=33 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=28 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=30 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM
|
-0.71 Grams per liter
Standard Deviation 0.94
|
-0.58 Grams per liter
Standard Deviation 0.75
|
-0.95 Grams per liter
Standard Deviation 1.57
|
0.02 Grams per liter
Standard Deviation 0.61
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (165). Only those participants with data available at specified timepoints has been presented (n=144).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Osteopontin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=35 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=35 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=33 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin
Baseline
|
305 Micrograms per liter
Standard Deviation 175
|
279 Micrograms per liter
Standard Deviation 118
|
286 Micrograms per liter
Standard Deviation 122
|
264 Micrograms per liter
Standard Deviation 130
|
|
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin
Day 85
|
335 Micrograms per liter
Standard Deviation 187
|
318 Micrograms per liter
Standard Deviation 131
|
350 Micrograms per liter
Standard Deviation 170
|
245 Micrograms per liter
Standard Deviation 115
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (165). Only those participants with data available at specified time points has been presented (n=119).
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Osteopontin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=28 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=33 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=28 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=30 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin
|
51 Micrograms per liter
Standard Deviation 130
|
36 Micrograms per liter
Standard Deviation 141
|
72 Micrograms per liter
Standard Deviation 83
|
-18 Micrograms per liter
Standard Deviation 119
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=143).
Serum samples were collected for the analysis total endogenous bile acids. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=32 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=42 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=34 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=35 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Total Endogenous Bile Acids
Baseline
|
11.011 Micromoles per liter
Standard Deviation 9.071
|
10.013 Micromoles per liter
Standard Deviation 12.860
|
16.048 Micromoles per liter
Standard Deviation 28.325
|
6.350 Micromoles per liter
Standard Deviation 9.524
|
|
Double-blind Phase: Absolute Values for Total Endogenous Bile Acids
Day 85
|
9.516 Micromoles per liter
Standard Deviation 14.945
|
5.948 Micromoles per liter
Standard Deviation 15.590
|
23.935 Micromoles per liter
Standard Deviation 54.351
|
8.796 Micromoles per liter
Standard Deviation 11.557
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=121).
Serum samples were collected for the analysis of total endogenous bile acids. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=25 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=38 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=29 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=29 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids
|
-4.489 Micromoles per liter
Standard Deviation 34.302
|
-3.018 Micromoles per liter
Standard Deviation 29.937
|
33.526 Micromoles per liter
Standard Deviation 153.176
|
0.525 Micromoles per liter
Standard Deviation 19.238
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=143).
FGF-19 is a protein secreted by the gastro-intestine under farnesoid X receptor (FXR) control. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=32 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=42 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=34 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=35 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19)
Baseline
|
102.9 Nanograms per liter
Standard Deviation 60.7
|
104.1 Nanograms per liter
Standard Deviation 64.5
|
115.7 Nanograms per liter
Standard Deviation 122.4
|
84.1 Nanograms per liter
Standard Deviation 56.1
|
|
Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19)
Day 85
|
248.2 Nanograms per liter
Standard Deviation 221.3
|
386.9 Nanograms per liter
Standard Deviation 443.9
|
2269.7 Nanograms per liter
Standard Deviation 9874.8
|
95.6 Nanograms per liter
Standard Deviation 65.6
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=126).
FGF-19 is a protein secreted by the gastro-intestine under FXR control. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=28 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=38 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=30 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=30 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Percent Change From Baseline Values for FGF19
|
161.0 Percent change
Standard Deviation 148.7
|
464.7 Percent change
Standard Deviation 1419.1
|
3029.2 Percent change
Standard Deviation 13234.0
|
75.9 Percent change
Standard Deviation 250.6
|
SECONDARY outcome
Timeframe: Baseline and Up to Day 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=153).
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. These eight dimensions can be summarized numerically into two scores: PCS and MCS; with score range from 0=worst to 100=best, with higher scores indicating better health. Increases from baseline indicate improvement. Baseline was defined as Day 0. Change from Baseline was defined as value of post Baseline minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=37 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=44 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=36 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=36 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale
PCS
|
-0.0 Scores on a scale
Standard Deviation 5.5
|
0.1 Scores on a scale
Standard Deviation 5.7
|
1.3 Scores on a scale
Standard Deviation 7.3
|
1.1 Scores on a scale
Standard Deviation 5.7
|
|
Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale
MCS
|
-2.2 Scores on a scale
Standard Deviation 7.0
|
-1.5 Scores on a scale
Standard Deviation 4.8
|
-1.2 Scores on a scale
Standard Deviation 10.0
|
1.7 Scores on a scale
Standard Deviation 9.3
|
SECONDARY outcome
Timeframe: Baseline and at 3, 6, 9 and 12 MonthsPopulation: ITT Population.
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. These eight dimensions can be summarized numerically into two scores: PCS and MCS; with score range from 0=worst to 100=best, with higher scores indicating better health. Increases from baseline indicate improvement. Baseline was defined as Day 85
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=78 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
Baseline, PCS
|
45.7 Scores on a scale
Standard Deviation 10.7
|
—
|
—
|
—
|
|
LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
12 Months, PCS
|
44.1 Scores on a scale
Standard Deviation 11.2
|
—
|
—
|
—
|
|
LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
Baseline, MCS
|
49.4 Scores on a scale
Standard Deviation 10.2
|
—
|
—
|
—
|
|
LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
12 Months, MCS
|
48.3 Scores on a scale
Standard Deviation 11.2
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and at Days 29, 57 and 85Population: Safety Population. Only those participants with data available at specified time points has been presented (n=163).
PBC-40 is a disease-specific quality of life questionnaire,which consists of 5 Domains(score ranges):general symptoms (score range 7-35), itch (3-15), fatigue (11-55), cognitive function (6-30) and emotional (1-15); higher scores indicated worse outcomes.The 40 questions from the PBC-40 questionnaire were scored from 1 (lowest impact of PBC on QoL) to 5 (representing highest impact); Higher scores indicate worse quality of life. Outcomes of 'never', 'not at all' or 'strongly agree' are scored with 1, 'always', 'very much' or 'strongly disagree' with 5, with following exceptions: For questions 34-39 outcomes were scored in reverse,i.e., 'strongly agree' with 5, and 'strongly disagree' with 1. If less than 50% of the questions per domain were not answered, missing values were imputed by mean of the available question scores for that domain.If for any item multiple answers are given, most severe was used. Baseline = Day 0. Change from Baseline=post Baseline minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=47 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=40 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
General symptoms, Day 29
|
-0.4 Scores on a scale
Standard Deviation 2.4
|
-0.9 Scores on a scale
Standard Deviation 2.5
|
0.3 Scores on a scale
Standard Deviation 2.1
|
-0.4 Scores on a scale
Standard Deviation 1.9
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
General symptoms, Day 57
|
0.1 Scores on a scale
Standard Deviation 2.7
|
-0.5 Scores on a scale
Standard Deviation 2.2
|
0.2 Scores on a scale
Standard Deviation 1.9
|
-0.3 Scores on a scale
Standard Deviation 2.3
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
General symptoms, Day 85
|
0.3 Scores on a scale
Standard Deviation 2.9
|
0.0 Scores on a scale
Standard Deviation 2.8
|
-0.1 Scores on a scale
Standard Deviation 2.8
|
-0.4 Scores on a scale
Standard Deviation 2.2
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Itch, Day 29
|
0.6 Scores on a scale
Standard Deviation 2.2
|
2.0 Scores on a scale
Standard Deviation 2.9
|
3.4 Scores on a scale
Standard Deviation 3.7
|
-0.2 Scores on a scale
Standard Deviation 1.7
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Itch, Day 57
|
0.6 Scores on a scale
Standard Deviation 2.7
|
2.0 Scores on a scale
Standard Deviation 3.0
|
2.9 Scores on a scale
Standard Deviation 2.9
|
-0.9 Scores on a scale
Standard Deviation 1.7
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Itch, Day 85
|
1.1 Scores on a scale
Standard Deviation 2.6
|
1.6 Scores on a scale
Standard Deviation 2.6
|
2.9 Scores on a scale
Standard Deviation 3.2
|
-0.8 Scores on a scale
Standard Deviation 2.3
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Fatigue, Day 29
|
-0.5 Scores on a scale
Standard Deviation 4.6
|
-1.3 Scores on a scale
Standard Deviation 5.1
|
-0.8 Scores on a scale
Standard Deviation 5.2
|
-2.6 Scores on a scale
Standard Deviation 4.2
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Fatigue, Day 57
|
-0.3 Scores on a scale
Standard Deviation 4.7
|
-0.6 Scores on a scale
Standard Deviation 5.0
|
-1.3 Scores on a scale
Standard Deviation 5.3
|
-3.5 Scores on a scale
Standard Deviation 6.3
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Fatigue, Day 85
|
-0.4 Scores on a scale
Standard Deviation 4.3
|
0.4 Scores on a scale
Standard Deviation 4.6
|
-0.3 Scores on a scale
Standard Deviation 5.3
|
-3.1 Scores on a scale
Standard Deviation 4.6
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Cognitive function, Day 29
|
-0.1 Scores on a scale
Standard Deviation 2.0
|
-0.5 Scores on a scale
Standard Deviation 2.0
|
0.6 Scores on a scale
Standard Deviation 3.1
|
-0.5 Scores on a scale
Standard Deviation 2.3
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Cognitive function, Day 57
|
-0.3 Scores on a scale
Standard Deviation 2.8
|
-0.2 Scores on a scale
Standard Deviation 2.8
|
0.2 Scores on a scale
Standard Deviation 3.0
|
-0.4 Scores on a scale
Standard Deviation 2.6
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Cognitive function, Day 85
|
-0.2 Scores on a scale
Standard Deviation 2.5
|
0.0 Scores on a scale
Standard Deviation 3.1
|
0.7 Scores on a scale
Standard Deviation 3.0
|
-0.3 Scores on a scale
Standard Deviation 3.0
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Emotional, Day 29
|
0.7 Scores on a scale
Standard Deviation 4.4
|
-1.1 Scores on a scale
Standard Deviation 3.6
|
-0.8 Scores on a scale
Standard Deviation 4.2
|
-0.3 Scores on a scale
Standard Deviation 4.8
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Emotional, Day 57
|
0.7 Scores on a scale
Standard Deviation 5.0
|
-0.1 Scores on a scale
Standard Deviation 4.6
|
-0.1 Scores on a scale
Standard Deviation 6.3
|
-1.0 Scores on a scale
Standard Deviation 5.1
|
|
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Emotional, Day 85
|
0.5 Scores on a scale
Standard Deviation 4.6
|
-0.6 Scores on a scale
Standard Deviation 3.7
|
-0.6 Scores on a scale
Standard Deviation 5.8
|
-1.3 Scores on a scale
Standard Deviation 4.9
|
SECONDARY outcome
Timeframe: Baseline and at 6 and 12 monthsPopulation: Safety Population (N=78). Only those participants with data available at specified time points has been presented (n=66).
PBC-40 is a disease-specific quality of life questionnaire, which consists of 5 Domains(score ranges):general symptoms (score range 7-35), itch (3-15), fatigue (11-55), cognitive function (6-30) and emotional (1-15); higher scores indicated worse outcomes.The 40 questions from the PBC-40 questionnaire were scored from 1 (lowest impact of PBC on QoL) to 5 (representing highest impact); Higher scores indicate worse quality of life. Outcomes of 'never', 'not at all' or 'strongly agree' are scored with 1, 'always', 'very much' or 'strongly disagree' with 5, with following exceptions: For questions 34-39 outcomes were scored in reverse,i.e., 'strongly agree' with 5, and 'strongly disagree' with 1. If less than 50% of the questions per domain were not answered, missing values were imputed by mean of the available question scores for that domain.If for any item multiple answers are given, most severe was used. Baseline = Day 85. Change from Baseline=post Baseline minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=66 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Cognitive function, 12 months
|
-0.4 Scores on a scale
Standard Deviation 3.3
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
General symptoms, 6 months
|
0.3 Scores on a scale
Standard Deviation 3.0
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
General symptoms, 12 months
|
0.3 Scores on a scale
Standard Deviation 2.7
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Itch, 6 months
|
1.2 Scores on a scale
Standard Deviation 3.6
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Itch, 12 months
|
0.5 Scores on a scale
Standard Deviation 3.3
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Fatigue, 6 months
|
-1.1 Scores on a scale
Standard Deviation 5.1
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Fatigue, 12 months
|
-1.7 Scores on a scale
Standard Deviation 5.4
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Cognitive function, 6 months
|
0.1 Scores on a scale
Standard Deviation 3.0
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Emotional, 6 months
|
-0.4 Scores on a scale
Standard Deviation 4.4
|
—
|
—
|
—
|
|
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Emotional, 12 months
|
-1.0 Scores on a scale
Standard Deviation 5.4
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and at Days 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=163).
5-D questionnaire has 5 domains: Duration, degree, direction, disability, distribution, and total score. Single item domain scores (duration, degree, direction)=range:1-5.Disability domain has 4 items=assess impact of itching on daily activities: sleep, leisure/social activities, housework/errands, work/school;score calculated as highest score on any of 4 items; disability domain range=1-5.For distribution domain only section "Mark whether itching has been present in following parts of your body over the last 2 weeks" was used. Number of affected body parts('present') is tallied(potential sum 0-16);sum was sorted into 5 scoring bins: sum 0-2= score 1,sum 3-5=score 2,sum 6-10=score 3, sum 11-13=score 4,sum 14-16=score 5. Distribution score range reported=1-5. For all domains, higher scores=worse outcomes. Total 5D score=summing domain scores; ranges:5(no pruritus) to25 (most severe pruritus); Higher scores=worse outcomes. Baseline=Day 0.Change from Baseline=post Baseline minus Baseline
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=47 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=40 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Disability, Day 57
|
0.4 Scores on a scale
Standard Deviation 1.1
|
0.6 Scores on a scale
Standard Deviation 1.1
|
0.8 Scores on a scale
Standard Deviation 1.2
|
-0.4 Scores on a scale
Standard Deviation 1.1
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Disability, Day 85
|
0.3 Scores on a scale
Standard Deviation 1.2
|
0.6 Scores on a scale
Standard Deviation 1.2
|
1.0 Scores on a scale
Standard Deviation 1.4
|
-0.4 Scores on a scale
Standard Deviation 1.2
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Distribution, Day 29
|
0.6 Scores on a scale
Standard Deviation 0.9
|
0.8 Scores on a scale
Standard Deviation 1.5
|
1.4 Scores on a scale
Standard Deviation 1.6
|
-0.2 Scores on a scale
Standard Deviation 0.9
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Distribution, Day 57
|
0.5 Scores on a scale
Standard Deviation 1.1
|
0.8 Scores on a scale
Standard Deviation 1.2
|
1.4 Scores on a scale
Standard Deviation 1.3
|
-0.2 Scores on a scale
Standard Deviation 0.8
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Distribution, Day 85
|
0.6 Scores on a scale
Standard Deviation 0.9
|
0.8 Scores on a scale
Standard Deviation 1.2
|
1.2 Scores on a scale
Standard Deviation 1.5
|
-0.2 Scores on a scale
Standard Deviation 1.0
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Total score, Day 29
|
2.6 Scores on a scale
Standard Deviation 3.4
|
3.0 Scores on a scale
Standard Deviation 4.7
|
4.4 Scores on a scale
Standard Deviation 5.4
|
-0.7 Scores on a scale
Standard Deviation 2.9
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Total score, Day 57
|
1.8 Scores on a scale
Standard Deviation 4.5
|
2.6 Scores on a scale
Standard Deviation 3.9
|
2.9 Scores on a scale
Standard Deviation 3.3
|
-1.8 Scores on a scale
Standard Deviation 3.0
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Total score, Day 85
|
1.3 Scores on a scale
Standard Deviation 3.8
|
1.7 Scores on a scale
Standard Deviation 4.0
|
4.2 Scores on a scale
Standard Deviation 5.1
|
-1.5 Scores on a scale
Standard Deviation 3.8
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Duration, Day 29
|
0.3 Scores on a scale
Standard Deviation 0.9
|
0.7 Scores on a scale
Standard Deviation 1.5
|
1.2 Scores on a scale
Standard Deviation 1.6
|
0.1 Scores on a scale
Standard Deviation 1.0
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Duration, Day 57
|
0.4 Scores on a scale
Standard Deviation 1.3
|
0.6 Scores on a scale
Standard Deviation 1.1
|
0.5 Scores on a scale
Standard Deviation 1.0
|
-0.3 Scores on a scale
Standard Deviation 0.7
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Duration, Day 85
|
0.2 Scores on a scale
Standard Deviation 0.8
|
0.4 Scores on a scale
Standard Deviation 1.1
|
0.8 Scores on a scale
Standard Deviation 1.2
|
-0.2 Scores on a scale
Standard Deviation 0.8
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Degree, Day 29
|
0.5 Scores on a scale
Standard Deviation 0.8
|
0.6 Scores on a scale
Standard Deviation 1.0
|
1.0 Scores on a scale
Standard Deviation 1.1
|
0.0 Scores on a scale
Standard Deviation 0.6
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Degree, Day 57
|
0.3 Scores on a scale
Standard Deviation 1.0
|
0.7 Scores on a scale
Standard Deviation 1.0
|
0.7 Scores on a scale
Standard Deviation 1.0
|
-0.2 Scores on a scale
Standard Deviation 0.8
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Degree, Day 85
|
0.4 Scores on a scale
Standard Deviation 0.9
|
0.6 Scores on a scale
Standard Deviation 1.0
|
0.9 Scores on a scale
Standard Deviation 1.1
|
-0.2 Scores on a scale
Standard Deviation 0.7
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Direction, Day 29
|
0.5 Scores on a scale
Standard Deviation 1.1
|
0.2 Scores on a scale
Standard Deviation 1.5
|
-0.2 Scores on a scale
Standard Deviation 1.6
|
-0.3 Scores on a scale
Standard Deviation 1.2
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Direction, Day 57
|
0.0 Scores on a scale
Standard Deviation 1.3
|
0.1 Scores on a scale
Standard Deviation 1.5
|
-0.2 Scores on a scale
Standard Deviation 1.4
|
-0.7 Scores on a scale
Standard Deviation 1.4
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Direction, Day 85
|
-0.2 Scores on a scale
Standard Deviation 1.5
|
-0.2 Scores on a scale
Standard Deviation 1.5
|
0.1 Scores on a scale
Standard Deviation 1.4
|
-0.5 Scores on a scale
Standard Deviation 1.5
|
|
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Disability, Day 29
|
0.7 Scores on a scale
Standard Deviation 1.2
|
0.7 Scores on a scale
Standard Deviation 1.2
|
1.3 Scores on a scale
Standard Deviation 1.5
|
-0.3 Scores on a scale
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: Up to Day 85Population: Safety Population.
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Any TEAE
|
34 Participants
|
47 Participants
|
41 Participants
|
32 Participants
|
|
Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Any SAE
|
0 Participants
|
1 Participants
|
5 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline and at Days 29, 57 and 85Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=152).
A VAS questionnaire was used to assess participant's pruritus. The pruritus VAS measures participant's perception of itch on a continuous scale with score ranged from 0 = no itching and 10 = worst possible itching; higher score indicates worse outcomes. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline was defined as value of post Baseline minus Baseline value.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=36 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=41 Participants
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=40 Participants
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=35 Participants
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS)
Day 29
|
11.5 Scores on a scale
Standard Deviation 19.5
|
17.8 Scores on a scale
Standard Deviation 26.3
|
22.8 Scores on a scale
Standard Deviation 33.2
|
-2.6 Scores on a scale
Standard Deviation 16.3
|
|
Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS)
Day 57
|
7.0 Scores on a scale
Standard Deviation 25.7
|
15.4 Scores on a scale
Standard Deviation 24.7
|
13.7 Scores on a scale
Standard Deviation 25.7
|
-10.7 Scores on a scale
Standard Deviation 19.6
|
|
Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS)
Day 85
|
6.5 Scores on a scale
Standard Deviation 22.2
|
12.9 Scores on a scale
Standard Deviation 24.5
|
17.2 Scores on a scale
Standard Deviation 28.9
|
-5.8 Scores on a scale
Standard Deviation 20.5
|
SECONDARY outcome
Timeframe: Up to 12 MonthsPopulation: Safety Population.
An AE was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Outcome measures
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=78 Participants
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
|---|---|---|---|---|
|
LTSE Phase: Number of Participants With TEAEs and SAEs
Any TEAE
|
76 Participants
|
—
|
—
|
—
|
|
LTSE Phase: Number of Participants With TEAEs and SAEs
Any SAE
|
5 Participants
|
—
|
—
|
—
|
Adverse Events
Obeticholic Acid (OCA) 10 Milligrams (mg)
Serious events: 0 serious events
Other events: 34 other events
Deaths: 0 deaths
OCA 25 mg
Serious events: 1 serious events
Other events: 47 other events
Deaths: 0 deaths
OCA 50 mg
Serious events: 5 serious events
Other events: 41 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 32 other events
Deaths: 0 deaths
LTSE OCA Total
Serious events: 5 serious events
Other events: 76 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 participants at risk
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 participants at risk
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 participants at risk
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 participants at risk
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
LTSE OCA Total
n=78 participants at risk
Participants from the double-blind phase entered the open-label LTSE phase of the study. A total of 7 participants entered the LTSE within 2 weeks of completing the double-blind phase. Participants initially started dosing at less than or equal to (\<=) 10 mg daily OCA and continued daily dosing at \>10 mg to ≤25 mg OCA. Entry of 71 participants from double-blind phase to LTSE phase was delayed up to 10 months due to administrative reasons.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.4%
1/41 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.4%
1/41 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
General disorders
Chest pain
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.4%
1/41 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Hepatobiliary disorders
Biliary cirrhosis primary
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.4%
1/41 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.4%
1/41 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Salivary gland neoplasm
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.1%
1/48 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.6%
1/38 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.4%
1/41 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
1.3%
1/78 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
1.3%
1/78 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Reproductive system and breast disorders
Cystocele
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
1.3%
1/78 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Reproductive system and breast disorders
Vaginal prolapse
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
1.3%
1/78 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
1.3%
1/78 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
Other adverse events
| Measure |
Obeticholic Acid (OCA) 10 Milligrams (mg)
n=38 participants at risk
Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85).
|
OCA 25 mg
n=48 participants at risk
Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
OCA 50 mg
n=41 participants at risk
Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
Placebo
n=38 participants at risk
Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85).
|
LTSE OCA Total
n=78 participants at risk
Participants from the double-blind phase entered the open-label LTSE phase of the study. A total of 7 participants entered the LTSE within 2 weeks of completing the double-blind phase. Participants initially started dosing at less than or equal to (\<=) 10 mg daily OCA and continued daily dosing at \>10 mg to ≤25 mg OCA. Entry of 71 participants from double-blind phase to LTSE phase was delayed up to 10 months due to administrative reasons.
|
|---|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Pruritus
|
47.4%
18/38 • Number of events 23 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
85.4%
41/48 • Number of events 52 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
80.5%
33/41 • Number of events 60 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
50.0%
19/38 • Number of events 21 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
87.2%
68/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Eye disorders
Dry Eye
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.2%
3/48 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
4.9%
2/41 • Number of events 2 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.6%
1/38 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Gastrointestinal disorders
Abdominal distension
|
5.3%
2/38 • Number of events 2 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.8%
4/41 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.6%
1/38 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.7%
6/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
General disorders
Constipation
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
8.3%
4/48 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.3%
3/41 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.0%
7/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
8.3%
4/48 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.3%
3/41 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
5.1%
4/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Gastrointestinal disorders
Nausea
|
10.5%
4/38 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.2%
3/48 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.8%
4/41 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.6%
1/38 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
5.1%
4/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.2%
3/48 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
General disorders
Fatigue
|
18.4%
7/38 • Number of events 8 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.2%
3/48 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
12.2%
5/41 • Number of events 7 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
13.2%
5/38 • Number of events 6 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
12.8%
10/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
General disorders
Pyrexia
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.0%
7/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.1%
1/48 • Number of events 2 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.8%
4/41 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.4%
5/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Nervous system disorders
Headache
|
7.9%
3/38 • Number of events 3 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
10.4%
5/48 • Number of events 7 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
17.1%
7/41 • Number of events 8 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
10.5%
4/38 • Number of events 6 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
10.3%
8/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.8%
4/41 • Number of events 5 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Oopharyngeal pain
|
5.3%
2/38 • Number of events 2 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
8.3%
4/48 • Number of events 4 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
2.6%
1/38 • Number of events 1 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
General disorders
Oedema Peripheral
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.4%
5/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
12.8%
10/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
9.0%
7/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Infections and infestations
Sinusitis
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.4%
5/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.4%
5/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
5.1%
4/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
10.3%
8/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
6.4%
5/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
12.8%
10/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/48 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/41 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
0.00%
0/38 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
7.7%
6/78 • AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.
AEs and SAEs were collected in Safety Population that comprised of all randomized participants who received at least 1 dose of investigational product.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All publications or lectures involving study material or data will be submitted for approval to Intercept Pharmaceuticals prior to submission to any journal/publication/lecture according to the clinical trial agreement.
- Publication restrictions are in place
Restriction type: OTHER