Trial Outcomes & Findings for Volixibat (SHP626) in the Treatment of Adults With Nonalcoholic Steatohepatitis (NASH) (NCT NCT02787304)
NCT ID: NCT02787304
Last Updated: 2019-11-25
Results Overview
Binary response indicating (yes/no) whether a subject responded at week 48 with a reduction of at least 2 points, without worsening of fibrosis, from baseline nonalcoholic fatty liver disease (NAFLD) activity score (NAS). The NAS grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and ballooning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
197 participants
Primary outcome timeframe
Baseline, Week 48
Results posted on
2019-11-25
Participant Flow
Participant milestones
| Measure |
SHP626 5 Milligram (mg)
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
49
|
50
|
49
|
49
|
|
Overall Study
COMPLETED
|
13
|
12
|
8
|
15
|
|
Overall Study
NOT COMPLETED
|
36
|
38
|
41
|
34
|
Reasons for withdrawal
| Measure |
SHP626 5 Milligram (mg)
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
9
|
3
|
8
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
4
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
1
|
|
Overall Study
Noncompliance with study drug
|
0
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
1
|
0
|
|
Overall Study
Study terminated by sponsor
|
25
|
31
|
31
|
32
|
Baseline Characteristics
Volixibat (SHP626) in the Treatment of Adults With Nonalcoholic Steatohepatitis (NASH)
Baseline characteristics by cohort
| Measure |
SHP626 5 Milligram (mg)
n=49 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=49 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=49 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=49 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
Total
n=196 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
52.8 years
STANDARD_DEVIATION 14.13 • n=5 Participants
|
53.0 years
STANDARD_DEVIATION 11.84 • n=7 Participants
|
53.2 years
STANDARD_DEVIATION 13.61 • n=5 Participants
|
53.4 years
STANDARD_DEVIATION 11.75 • n=4 Participants
|
53.1 years
STANDARD_DEVIATION 12.78 • n=21 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
118 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
163 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
46 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
175 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 48Population: Full Analysis Set for subjects with liver biopsy at both Baseline and Week 48 (post hoc analysis) at the time of the interim analysis
Binary response indicating (yes/no) whether a subject responded at week 48 with a reduction of at least 2 points, without worsening of fibrosis, from baseline nonalcoholic fatty liver disease (NAFLD) activity score (NAS). The NAS grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and ballooning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=11 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=11 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=8 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=13 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Number of Subjects Achieving Binary Response on Liver Histology Between Volixibat (SHP626) and Placebo at Week 48
|
4 Participants
|
2 Participants
|
3 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set for subjects with liver biopsy at both Baseline and Week 48 (post hoc analysis) at the time of the interim analysis
Change in liver histology will be measured by the individual NAS components (ballooning, inflammation, steatosis). The NAS grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and ballooning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis (assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=11 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=11 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=8 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=13 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Liver Histology
NAS - steatosis
|
-0.5 score on a scale
Standard Deviation 0.82
|
-0.2 score on a scale
Standard Deviation 0.87
|
-0.5 score on a scale
Standard Deviation 0.93
|
-0.3 score on a scale
Standard Deviation 0.85
|
|
Change From Baseline to Week 48 on Liver Histology
NAS - ballooning
|
-0.3 score on a scale
Standard Deviation 0.9
|
-0.2 score on a scale
Standard Deviation 0.75
|
0.0 score on a scale
Standard Deviation 0.93
|
-0.7 score on a scale
Standard Deviation 0.85
|
|
Change From Baseline to Week 48 on Liver Histology
NAS - inflammation
|
-0.2 score on a scale
Standard Deviation 0.75
|
-0.5 score on a scale
Standard Deviation 0.93
|
-0.5 score on a scale
Standard Deviation 0.76
|
-0.7 score on a scale
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set (post hoc analysis) - for subjects with Week 48 data at the time of interim analysis
Change in hepatic steatosis will be evaluated by measuring the reduction of liver fat with magnetic resonance imaging-proton density fat-fraction (MRI-PDFF) and stratified by treatment group.
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=13 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=12 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=8 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=13 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Hepatic Steatosis
|
-2.68 absolute percentage
Standard Deviation 4.801
|
-1.31 absolute percentage
Standard Deviation 7.555
|
-3.89 absolute percentage
Standard Deviation 4.474
|
-1.34 absolute percentage
Standard Deviation 5.478
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Full Analysis Set for subjects with liver biopsy at both Baseline and Week 48 (post hoc analysis) at the time of the interim analysis
Change in liver histology will be measured by fibrosis stage. Fibrosis stage is assessed on a scale of 0-4 with higher scores indicating more severe disease and lower scores indicating less severe disease (F0 = no fibrosis, F4 = cirrhosis).
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=11 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=11 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=8 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=13 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Liver Histology
Fibrosis Score Baseline
|
1.8 units on a scale
Standard Deviation 1.08
|
2.2 units on a scale
Standard Deviation 0.98
|
1.5 units on a scale
Standard Deviation 1.07
|
1.4 units on a scale
Standard Deviation 0.96
|
|
Change From Baseline to Week 48 on Liver Histology
Fibrosis Score Week 48
|
1.5 units on a scale
Standard Deviation 1.13
|
2.2 units on a scale
Standard Deviation 1.25
|
2.1 units on a scale
Standard Deviation 1.25
|
1.3 units on a scale
Standard Deviation 0.95
|
SECONDARY outcome
Timeframe: Week 48Population: Safety Analysis Set for subjects with liver biopsy at both Baseline and Week 48 (post hoc analysis) at the time of the interim analysis
Resolution of NASH is defined as total absence of ballooning \[score = 0\], absent or mild inflammation \[score 0-1\], steatosis can be present \[score 0-3\]) without worsening of fibrosis as assessed by liver histology at Week 48.
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=11 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=11 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=8 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=13 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Number of Participants With Resolution of NASH at Week 48
|
2 Participants
|
3 Participants
|
2 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set (post hoc analysis) - for subjects with Week 48 data at the time of interim analysis
Serum liver-related biochemistry will be analysed by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT).
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=18 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=16 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=15 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=20 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Serum Liver-related Biochemistry
GGT change from Baseline
|
8.8 U/L
Standard Deviation 46.24
|
5.2 U/L
Standard Deviation 47.24
|
-8.8 U/L
Standard Deviation 45.43
|
-8.5 U/L
Standard Deviation 41.11
|
|
Change From Baseline to Week 48 on Serum Liver-related Biochemistry
ALT change from Baseline
|
1.2 U/L
Standard Deviation 25.83
|
4.2 U/L
Standard Deviation 33.65
|
-6.9 U/L
Standard Deviation 37.91
|
-0.2 U/L
Standard Deviation 24.93
|
|
Change From Baseline to Week 48 on Serum Liver-related Biochemistry
AST change from Baseline
|
7.6 U/L
Standard Deviation 16.57
|
10.6 U/L
Standard Deviation 31.23
|
-7.2 U/L
Standard Deviation 27.08
|
-0.8 U/L
Standard Deviation 14.45
|
|
Change From Baseline to Week 48 on Serum Liver-related Biochemistry
ALP change from Baseline
|
5.3 U/L
Standard Deviation 9.62
|
-0.9 U/L
Standard Deviation 27.37
|
-0.1 U/L
Standard Deviation 14.82
|
-0.7 U/L
Standard Deviation 10.66
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set (post hoc analysis) - for subjects with Week 48 data at the time of interim analysis
Serum liver-related biochemistry will be analysed by measuring total bilirubin (TB).
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=18 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=16 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=15 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=20 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Serum Liver-related Biochemistry
|
0.019 mg/dL
Standard Deviation 0.2198
|
0.124 mg/dL
Standard Deviation 0.2872
|
0.060 mg/dL
Standard Deviation 0.2730
|
0.058 mg/dL
Standard Deviation 0.1762
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set (post hoc analysis) - for subjects with Week 48 data at the time of interim analysis. For insulin levels, samples were collected but due to study termination for futility after the interim analysis, an analysis of this outcome measure was not performed.
Metabolic indicators will be assessed by measuring fasting serum glucose levels and insulin levels.
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=18 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=16 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=15 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=20 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Metabolic Indicators
|
3.5 mg/dL
Standard Deviation 40.07
|
-5.0 mg/dL
Standard Deviation 23.11
|
1.6 mg/dL
Standard Deviation 21.31
|
15.6 mg/dL
Standard Deviation 45.84
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set (post hoc analysis) - for subjects with Week 48 data at the time of interim analysis.
Metabolic indicators will be assessed by measuring hemoglobin A1c (HbA1c).
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=18 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=16 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=15 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=20 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Metabolic Indicators
|
-0.0003 percentage of glycated hemoglobin
Standard Deviation 0.00559
|
-0.0008 percentage of glycated hemoglobin
Standard Deviation 0.00552
|
-0.0020 percentage of glycated hemoglobin
Standard Deviation 0.00426
|
0.0033 percentage of glycated hemoglobin
Standard Deviation 0.00701
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Safety Analysis Set (post hoc analysis) - for subjects with Week 48 data at the time of interim analysis
Serum lipids level will be measured by calculating fasting total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides.
Outcome measures
| Measure |
SHP626 5 Milligram (mg)
n=18 Participants
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=16 Participants
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=15 Participants
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=20 Participants
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Change From Baseline to Week 48 on Serum Lipids
Triglycerides change from Baseline
|
-9.5 mg/dL
Standard Deviation 37.05
|
-0.2 mg/dL
Standard Deviation 92.34
|
-7.2 mg/dL
Standard Deviation 71.62
|
28.7 mg/dL
Standard Deviation 52.48
|
|
Change From Baseline to Week 48 on Serum Lipids
Fasting total cholesterol change from Baseline
|
-13.4 mg/dL
Standard Deviation 32.06
|
-19.1 mg/dL
Standard Deviation 38.26
|
-7.6 mg/dL
Standard Deviation 26.94
|
4.7 mg/dL
Standard Deviation 30.38
|
|
Change From Baseline to Week 48 on Serum Lipids
HDL-C change from Baseline
|
1.8 mg/dL
Standard Deviation 6.72
|
2.2 mg/dL
Standard Deviation 10.36
|
2.7 mg/dL
Standard Deviation 6.56
|
0.0 mg/dL
Standard Deviation 6.74
|
|
Change From Baseline to Week 48 on Serum Lipids
LDL-C change from Baseline
|
-13.4 mg/dL
Standard Deviation 27.38
|
-19.5 mg/dL
Standard Deviation 31.78
|
-9.0 mg/dL
Standard Deviation 22.37
|
-0.8 mg/dL
Standard Deviation 26.12
|
Adverse Events
SHP626 5 Milligram (mg)
Serious events: 1 serious events
Other events: 44 other events
Deaths: 0 deaths
SHP626 10 Milligram (mg)
Serious events: 2 serious events
Other events: 44 other events
Deaths: 0 deaths
SHP626 20 Milligram (mg)
Serious events: 0 serious events
Other events: 42 other events
Deaths: 0 deaths
Placebo (PBO)
Serious events: 1 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SHP626 5 Milligram (mg)
n=49 participants at risk
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=49 participants at risk
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=49 participants at risk
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=49 participants at risk
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
General disorders
Chest pain
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Nervous system disorders
Seizures
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Nervous system disorders
Syncope
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
Other adverse events
| Measure |
SHP626 5 Milligram (mg)
n=49 participants at risk
Subject will be administered 5 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 10 Milligram (mg)
n=49 participants at risk
Subject will be administered 10 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
SHP626 20 Milligram (mg)
n=49 participants at risk
Subject will be administered 20 mg SHP626 capsule by orally once daily in a double-blinded fashion
SHP626: 5 mg, 10 mg, and 20 mg of SHP626 capsule by orally once daily in a double-blinded fashion
|
Placebo (PBO)
n=49 participants at risk
Subject will be administered SHP626 matching PBO capsule by orally once daily in a double-blinded fashion
Placebo: Matching placebo
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
77.6%
38/49 • Number of events 43 • Up to Visit 10 (Week 52)
|
71.4%
35/49 • Number of events 46 • Up to Visit 10 (Week 52)
|
71.4%
35/49 • Number of events 47 • Up to Visit 10 (Week 52)
|
20.4%
10/49 • Number of events 11 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Abdominal pain
|
20.4%
10/49 • Number of events 11 • Up to Visit 10 (Week 52)
|
18.4%
9/49 • Number of events 10 • Up to Visit 10 (Week 52)
|
12.2%
6/49 • Number of events 6 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Nausea
|
10.2%
5/49 • Number of events 6 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 6 • Up to Visit 10 (Week 52)
|
14.3%
7/49 • Number of events 7 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Constipation
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Frequent bowel movements
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Gastrointestinal disorders
Abdominal distension
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Urinary tract infection
|
2.0%
1/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
14.3%
7/49 • Number of events 8 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Upper respiratory tract infection
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Influenza
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Nasopharyngitis
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 5 • Up to Visit 10 (Week 52)
|
|
Infections and infestations
Sinusitis
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Investigations
Vitamin D decreased
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
|
Investigations
Blood creatine phosphokinase increased
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
General disorders
Fatigue
|
6.1%
3/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
|
General disorders
Oedema peripheral
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Nervous system disorders
Dizziness
|
4.1%
2/49 • Number of events 2 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 5 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
|
Nervous system disorders
Headache
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
8.2%
4/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
4.1%
2/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
2.0%
1/49 • Number of events 1 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 4 • Up to Visit 10 (Week 52)
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
6.1%
3/49 • Number of events 3 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
0.00%
0/49 • Up to Visit 10 (Week 52)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place