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Study of INT-747 as Monotherapy in Patients With PBC

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ClinicalTrials.gov Identifier: NCT00570765
Recruitment Status : Completed
First Posted : December 11, 2007
Results First Posted : July 7, 2011
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Liver Cirrhosis, Biliary
Interventions Drug: Placebo
Drug: INT-747
Enrollment 59
Recruitment Details Recruitment started Dec. 2007 and completed June 2010. Due to positive Phase 2 data in another study (747-202), power calculations were revised and recruitment ended early.
Pre-assignment Details Screening interim allowed for pre-randomization eligibility assessment of 1 to 4 weeks. Other than 3-month (pre-Screening) washout for ursodeoxycholic acid (UDCA) and other medications, no washout or run-in period was defined between Screening and randomization.
Arm/Group Title 10 mg 50 mg Placebo
Hide Arm/Group Description INT-747 10 mg by mouth, daily INT-747 50 mg by mouth, daily Placebo by mouth, daily
Period Title: Overall Study
Started 20 16 23
Completed 16 9 23
Not Completed 4 7 0
Arm/Group Title 10 mg 50 mg Placebo Total
Hide Arm/Group Description INT-747 10 mg by mouth, daily INT-747 50 mg by mouth, daily Placebo by mouth, daily Total of all reporting groups
Overall Number of Baseline Participants 20 16 23 59
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 16 participants 23 participants 59 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
16
  80.0%
15
  93.8%
18
  78.3%
49
  83.1%
>=65 years
4
  20.0%
1
   6.3%
5
  21.7%
10
  16.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 16 participants 23 participants 59 participants
54.8  (10.9) 54.1  (7.3) 55.3  (10.0) 54.8  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 16 participants 23 participants 59 participants
Female
14
  70.0%
16
 100.0%
20
  87.0%
50
  84.7%
Male
6
  30.0%
0
   0.0%
3
  13.0%
9
  15.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants 16 participants 23 participants 59 participants
France 2 1 1 4
United States 4 5 8 17
Canada 3 2 4 9
Spain 0 1 1 2
Germany 4 1 3 8
United Kingdom 7 6 6 19
1.Primary Outcome
Title Alkaline Phosphatase (AP) Levels
Hide Description Percent (%) Change in Serum Alkaline Phosphatase from baseline to end of study (EOS)at Day 85.
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Per Statistical Analysis Plan (SAP): patients will be analyzed by the treatment group to which they were randomly assigned - intention to treat (ITT) principle.
Arm/Group Title 10 mg 50 mg Placebo
Hide Arm/Group Description:
INT-747 10 mg by mouth, daily
INT-747 50 mg by mouth, daily
Placebo by mouth, daily
Overall Number of Participants Analyzed 20 16 23
Mean (Standard Error)
Unit of Measure: Percent change
-44.5  (5.5) -37.6  (5.3) 0.4  (3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10 mg, 50 mg, Placebo
Comments Hierarchical testing strategy is proposed to account for multiple comparisons. The statistical significance will be evaluated as follows: if statistical significance at alpha=0.05 is shown for the 10mg INT-747 vs. placebo, then we may proceed to evaluate the statistical significance at alpha=0.05 for the 50mg INT-747 versus placebo. If no stat. significance is shown at alpha=0.05 at the first step, then the subsequent comparison should not be considered statistically significant.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Tx arms will be compared using the 2-sided Wilcoxon-Mann-Whitney test, at 5% significance level. Tx groups will be pairwise compared vs. placebo.
2.Secondary Outcome
Title Hepatocellular Injury and Liver Function: GGT
Hide Description Percent change of gamma-glutamyl transferase (GGT)from Baseline (Day 0) vs. Day 85/ or early termination (ET) visit.
Time Frame Baeline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 10 mg 50 mg Placebo
Hide Arm/Group Description:
INT-747 10 mg by mouth, daily
INT-747 50 mg by mouth, daily
Placebo by mouth, daily
Overall Number of Participants Analyzed 20 16 23
Mean (Standard Error)
Unit of Measure: Percent change
-73  (4) -65  (6) -3  (5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10 mg, 50 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Tx arms will be compared using the 2-sided Wilcoxon-Mann-Whitney test, at 5% significance level. Tx groups will be pairwise compared vs. placebo.
3.Secondary Outcome
Title Hepatocellular Injury and Liver Function: ALT
Hide Description Percent change of alanine transaminase(ALT)from Baseline (Day 0) vs. Day 85/ or early termination.
Time Frame Baeline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 10 mg 50 mg Placebo
Hide Arm/Group Description:
INT-747 10 mg by mouth, daily
INT-747 50 mg by mouth, daily
Placebo by mouth, daily
Overall Number of Participants Analyzed 20 16 23
Mean (Standard Error)
Unit of Measure: Percent change
-37  (8) -35  (7) -4  (9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10 mg, 50 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Tx arms will be compared using the 2-sided Wilcoxon-Mann-Whitney test, at 5% significance level. Tx groups will be pairwise compared vs. placebo.
4.Secondary Outcome
Title Plasma Trough Concentrations of INT-747 and Its Major, Known Metabolites
Hide Description [Not Specified]
Time Frame 12 weeks
Outcome Measure Data Not Reported
Time Frame Adverse events were collected starting when the patient took the first dose of study medication (following Day 0) and during study participation, through the follow-up visit at Day 99.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 10 mg 50 mg Placebo
Hide Arm/Group Description INT-747 10 mg by mouth, daily INT-747 50 mg by mouth, daily Placebo by mouth, daily
All-Cause Mortality
10 mg 50 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
10 mg 50 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      0/16 (0.00%)      1/23 (4.35%)    
Skin and subcutaneous tissue disorders       
rash * 1 [1]  0/20 (0.00%)  0 0/16 (0.00%)  0 1/23 (4.35%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
[1]
Patient hospitalized due to hypersensitivity to opioid.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
10 mg 50 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/20 (70.00%)      15/16 (93.75%)      8/23 (34.78%)    
Gastrointestinal disorders       
abdominal pain * 1  1/20 (5.00%)  1 2/16 (12.50%)  2 1/23 (4.35%)  1
diarrhoea * 1  0/20 (0.00%)  0 2/16 (12.50%)  2 1/23 (4.35%)  1
nausea * 1  0/20 (0.00%)  0 4/16 (25.00%)  4 4/23 (17.39%)  5
vomiting * 1  1/20 (5.00%)  1 1/16 (6.25%)  1 1/23 (4.35%)  1
General disorders       
fatigue * 1  0/20 (0.00%)  0 1/16 (6.25%)  1 3/23 (13.04%)  3
influenza like illness * 1  0/20 (0.00%)  0 1/16 (6.25%)  1 2/23 (8.70%)  2
Infections and infestations       
nasopharyngitis * 1  3/20 (15.00%)  3 1/16 (6.25%)  1 2/23 (8.70%)  2
urinary tract infection * 1  3/20 (15.00%)  3 1/16 (6.25%)  1 0/23 (0.00%)  0
Musculoskeletal and connective tissue disorders       
back pain * 1  0/20 (0.00%)  0 0/16 (0.00%)  0 4/23 (17.39%)  4
Nervous system disorders       
dizziness * 1  0/20 (0.00%)  0 0/16 (0.00%)  0 4/23 (17.39%)  5
headache * 1  4/20 (20.00%)  5 2/16 (12.50%)  3 5/23 (21.74%)  6
Psychiatric disorders       
insomnia * 1  1/20 (5.00%)  2 2/16 (12.50%)  2 1/23 (4.35%)  1
Respiratory, thoracic and mediastinal disorders       
cough * 1  1/20 (5.00%)  1 1/16 (6.25%)  1 1/23 (4.35%)  1
Skin and subcutaneous tissue disorders       
pruritus * 1  14/20 (70.00%)  24 15/16 (93.75%)  22 8/23 (34.78%)  12
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Per protocol, Intercept retains ownership of the study data. Proposed publications based on the study shall be approved prior to submission for publications and will not be unreasonably withheld.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Cathi Sciacca, Sr. Director, Clinical Operations
Organization: Intercept Pharmaceuticals, Inc.
Phone: 858-652-6803
EMail: csciacca@interceptpharma.com
Layout table for additonal information
Responsible Party: Intercept Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00570765     History of Changes
Other Study ID Numbers: 747-201
First Submitted: December 7, 2007
First Posted: December 11, 2007
Results First Submitted: June 9, 2011
Results First Posted: July 7, 2011
Last Update Posted: April 3, 2018