12 Week Efficacy and Safety Trial Followed by a 4 Week Withdrawal Period for Patients with Chronic Idiopathic Constipation.
The present trial was designed to determine the efficacy and safety of elobixibat treatment (at both doses of 5 mg and 10 mg/day) compared to placebo treatment for 12-week Treatment Period followed by a 4-week Withdrawal Period in patients with chronic idiopathic constipation. During Withdrawal Period a sub-group of patients in elobixibat 5 mg and 10 mg treatment arms respectively received placebo treatment, while rest of the patients continued with 5 mg and 10 mg treatment in respective groups. In placebo groups, patients received elobixibat 10 mg treatment during Withdrawal Period. Patients were followed-up for 2 weeks after end of the Withdrawal Period. The assessment of primary and key secondary end points was done for patients who completed the first 12 weeks of treatment period. Incidence of Adverse Events (AEs) were reported till 2 weeks after end of the Withdrawal Period. The trial was early terminated due to a distribution issue with the trial medication.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
314
Overall Complete Spontaneous Bowel Movement (CSBM) Response
This outcome measured the percentage of patients who were CSBM responders. A CSBM responder was defined as a patient with ≥3 CSBMs per week and an increase of ≥1 CSBM per week from Baseline, for at least 9 of the 12 weeks in the 12-week Treatment Period, including at least 3 weeks during Weeks 9-12.
Time frame: During the first 12 weeks
Occurrence of CSBM Response
This outcome measured the percentage of patients who had a CSBM within 24 hours after the first dose of treatment. A CSBM was defined as a spontaneous (occurring without laxative within the preceding 24 hours, including no rescue medication within the preceding 24 hours) bowel movement (as interpreted by the patient, with a beginning and an end, including single or multiple stools), accompanied by a patient reported sense of complete evacuation ('complete').
Time frame: Within first 24 hours of treatment initiation
Change From Baseline in Weekly Frequency of Spontaneous Bowel Movement (SBMs)
The change from Baseline for the continuous variable was estimated using a repeated measures analysis of covariance (ANCOVA) model.
Time frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Change From Baseline in Weekly Stool Consistency of SBMs
The stool consistency is measured using the seven-point ordinal Bristol Stool Form Scale (BSFS) score. The BSFS classifies human stool into seven types and points them accordingly. Type 1: Separate hard lumps, like nuts (hard to pass) Type 2: Sausage-shaped, but lumpy Type 3: Like a sausage but with cracks on its surface Type 4: Like a sausage or snake, smooth and soft Type 5: Soft blobs with clear cut edges (passed easily) Type 6: Fluffy pieces with ragged edges, a mushy stool Type 7: Watery, no solid pieces, entirely liquid Types 1 and 2 indicate constipation, with 3 and 4 represents the ideal stool form (especially the latter), and 5, 6 and 7 tends towards diarrhoea . For a given assessment week, the weekly stool consistency was defined as the sum of non-missing stool consistency score for SBMs during that week divided by the number of non-missing stool consistency score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.
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Birmingham Gastroenterology Associates, PC
Birmingham, Alabama, United States
Genova Clinical Research, Inc.
Tucson, Arizona, United States
Preferred Research Partners
Little Rock, Arkansas, United States
Arkansas Gastroenterology
North Little Rock, Arkansas, United States
David Geffen School of Medicine at University of California, Los Angeles
Los Angeles, California, United States
West Gastroenterology Associates
Los Angeles, California, United States
Sacramento Research Medical Group
Sacramento, California, United States
Precision Research Institute, LLC
San Diego, California, United States
Gastroenterology Associates of Fairfield County
Bridgeport, Connecticut, United States
Zasa Clinical Research
Boynton Beach, Florida, United States
...and 87 more locations
Time frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Total Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score Responder
This outcome measured the percentage of patients who were PAC-QOL score responder at 12-week Treatment Period. A PAC-QOL score responder was defined as a patient with ≥50% reduction in total PAC-QOL score from Baseline at Week 12. PAC-QOL is a 28-item questionnaire for psychometric assessment of disease-specific quality of life. The questionnaire is based on 5-point Likert scale; ranging from 0 \[none of the time or not at all\] to 4 \[all of the time or extremely\]). A lower score indicates a better Quality of Life. The PAC-QOL questionnaire is developed specifically for patients with constipation. Total PAC-QOL score was averaged from the individual item score.
Time frame: At Week 12
Change From Baseline in Weekly Degree of Straining of SBMs
The degree of straining was measured using the five-point ordinal scale (1=Not at all, 2=A little bit, 3=A moderate amount, 4=A great deal, and 5=An extreme amount). For a given assessment week, the weekly degree of straining was defined as the sum of non-missing straining score for SBMs during that week divided by the number of non-missing straining score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.
Time frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Change From Baseline in Weekly Abdominal Bloating Score
The abdominal pain score was measured using the five-point ordinal scale (1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very severe). For a given assessment week, the weekly abdominal bloating score was defined as the sum of non-missing abdominal bloating score for SBMs during that week divided by the number of non-missing abdominal bloating score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.
Time frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period
Change From Baseline in Weekly Abdominal Discomfort Score
The abdominal discomfort score was measured using the five-point ordinal scale (1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very severe). For a given assessment week, the weekly abdominal discomfort score was defined as the sum of non-missing abdominal discomfort score for SBMs during that week divided by the number of non-missing abdominal discomfort score for SBMs during that week. The parameter was analysed using repeated measures ANCOVA model.
Time frame: From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period