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Obeticholic Acid in Bile Acid Diarrhoea (OBADIAH1)

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ClinicalTrials.gov Identifier: NCT01585025
Recruitment Status : Completed
First Posted : April 25, 2012
Results First Posted : September 13, 2019
Last Update Posted : March 10, 2020
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Primary Bile Acid Malabsorption
Secondary Bile Acid Malabsorption
Chronic Diarrhoea
Intervention Drug: Obeticholic acid
Enrollment 35
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection With Crohn's disease or ileal resection Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Period Title: Overall Study
Started 10 13 12
Completed 10 10 8
Not Completed 0 3 4
Reason Not Completed
Withdrawal by Subject             0             3             4
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls Total
Hide Arm/Group Description Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection With Crohn's disease or ileal resection Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection Total of all reporting groups
Overall Number of Baseline Participants 10 10 8 28
Hide Baseline Analysis Population Description
Received any dose of medication
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 8 participants 28 participants
47
(24 to 74)
45
(27 to 71)
39
(25 to 68)
41
(24 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 8 participants 28 participants
Female
7
  70.0%
7
  70.0%
3
  37.5%
17
  60.7%
Male
3
  30.0%
3
  30.0%
5
  62.5%
11
  39.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 10 participants 10 participants 8 participants 28 participants
10 10 8 28
1.Primary Outcome
Title Changes in Fasting FGF19
Hide Description The primary outcome measure is the change over 2 weeks in fasting serum fibroblast growth factor (FGF19) in 3 groups of patients: primary bile acid diarrhoea, secondary bile acid diarrhoea, and a control population of patients with chronic diarrhoea but with normal bile acid retention.
Time Frame Day 0, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 10 10 8
Median (Inter-Quartile Range)
Unit of Measure: percentage increase of baseline
71
(9 to 102)
25
(-6 to 140)
130
(-14 to 304)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Paired comparison of fasting FGF19 at baseline on day 0 and on day 14 of OCA treatment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Paired comparison of fasting FGF19 at baseline on day 0 and on day 14 of OCA treatment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Paired comparison of fasting FGF19 at baseline on day 0 and on day 14 of OCA treatment
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Changes in Non-fasting Response of FGF19 to OCA
Hide Description Change in dynamic response of FGF19 in 6 hours following OCA administration; at start and end of 15 day OCA test period.
Time Frame Day 0, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 10 10 8
Median (Inter-Quartile Range)
Unit of Measure: percentage change
11.6
(-23.6 to 57.8)
14.6
(-22.7 to 49.0)
32.4
(15.1 to 38.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Change in FGF19 AUC
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Change in FGF19 AUC
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Change in FGF19 AUC
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Secondary Outcome
Title Changes in Fasting 7α-hydroxy-4-cholesten-3-one
Hide Description Change in fasting 7α-hydroxy-4-cholesten-3-one before and after 15 day administration of OCA.
Time Frame Day 0, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data in Primary BAD
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 8 10 8
Median (Inter-Quartile Range)
Unit of Measure: microgram/L
-11.5
(-30.0 to -3.5)
-27.5
(-56.3 to 0)
-6.5
(-11.5 to -1.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Change in fasting C4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Change in fasting C4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Change in fasting C4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Changes in Serum Total Bile Acids.
Hide Description Dynamic changes of total bile acids over 6 hour period following OCA administration before and after 15 day OCA period.
Time Frame Day 0, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 10 10 8
Median (Inter-Quartile Range)
Unit of Measure: micromol/L
-18.1
(-33.0 to -5.50)
-2.0
(-17.5 to 0.08)
-15.5
(-17.9 to -14.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Change in bile acid 6h AUC
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Change in bile acid 6h AUC
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Change in bile acid 6h AUC
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Changes in Stool Frequency
Hide Description Change in total number of stool episodes reported per week between week 2 (baseline) and week 4 (week 2 of treatment)
Time Frame Week 2, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data in Idiopathic diarrhoea controls
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 10 10 7
Median (Inter-Quartile Range)
Unit of Measure: stools per week
-4.5
(-9.3 to -1.5)
-2.5
(-15.8 to 1.8)
3.0
(-3.0 to 7.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Comparison of change in number of stools per week
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Comparison of change in number of stools per week
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Comparison of change in number of stools per week
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Changes in Mean Stool Form
Hide Description Change in mean stool form reported per week between week 2 (baseline) and week 4 (week 2 of treatment) using the Bristol Stool Form Scale (range of scores 1 to 7). High scores are a worse outcome (7=liquid stools).
Time Frame Week 2, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data in Idiopathic diarrhoea controls
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 10 10 7
Median (Inter-Quartile Range)
Unit of Measure: Score on Bristol scale
-0.71
(-1.54 to 0.10)
-0.38
(-0.91 to -0.18)
-0.46
(-0.91 to 0.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Change in median stool form
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Change in median stool form
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Change in median stool form
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Change in Stool Index
Hide Description

Change in index calculated on a weekly basis, between week 2 (baseline) and week 4 (week 2 of treatment).

Index calculated as ([weekly stool frequency x mean Bristol Stool Form Scale score] = Loperamide use [weekly mg x 3]).

Individual scores ranged from 25 to 1095, with higher scores being worst.

Time Frame Week 2, Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Missing data in Idiopathic diarrhoea controls
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description:
Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection
With Crohn's disease or ileal resection
Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
Overall Number of Participants Analyzed 10 10 7
Median (Inter-Quartile Range)
Unit of Measure: index score
-37.5
(-52.3 to -22.8)
-32.5
(-158.6 to -13.4)
-5.5
(-30.0 to 20.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Primary BAD
Comments Paired difference in weekly index score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secondary BAD
Comments Paired difference in weekly index score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Idiopathic Diarrhoea Controls
Comments Paired difference in weekly index score
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame Data were collected over the 6 weeks of the trial
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Hide Arm/Group Description Defined as SeHCAT <10% without other causes such as Crohn's disease and/or ileal resection With Crohn's disease or ileal resection Chronic diarrhoea with SeHCAT >15% and no Crohn's or ileal resection
All-Cause Mortality
Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/10 (0.00%)      0/8 (0.00%)    
Hide Serious Adverse Events
Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)      0/8 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Primary BAD Secondary BAD Idiopathic Diarrhoea Controls
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      3/10 (30.00%)      1/8 (12.50%)    
Gastrointestinal disorders       
Constipation/abdominal pain *  0/10 (0.00%)  0 1/10 (10.00%)  1 0/8 (0.00%)  0
Nervous system disorders       
Headache *  0/10 (0.00%)  0 2/10 (20.00%)  2 1/8 (12.50%)  1
*
Indicates events were collected by non-systematic assessment
Recruitment in the idiopathic chronic diarrhoea control group did not reach the prespecified number of 10 due to dropouts. Of the 8 subjects recruited, one failed to return diaries that could be analysed.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof Julian Walters
Organization: Imperial College London
Phone: +442033132361
EMail: julian.walters@imperial.ac.uk
Publications:
Layout table for additonal information
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01585025    
Other Study ID Numbers: CRO1909
2011-003777-28 ( EudraCT Number )
First Submitted: April 23, 2012
First Posted: April 25, 2012
Results First Submitted: March 20, 2019
Results First Posted: September 13, 2019
Last Update Posted: March 10, 2020