Functional Constipation
Conditions
Keywords
Pradigastat, Proof of Concept, Functional Constipation
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of pradigastat 20 and 40 mg as compared to placebo in patients with Functional Constipation.
Detailed description
This multicenter, randomized, placebo-controlled, double-blind study is designed to demonstrate the efficacy, safety and tolerability of pradigastat relative to placebo across 2 doses (20 and 40 mg) for up to 6 weeks (4-week treatment, 2-week Follow-up) in patients with Functional Constipation. The primary endpoint is the change from baseline in the number of weekly spontaneous bowel movement (SBM), the key secondary endpoint is the change from baseline in the number of weekly complete spontaneous bowel movement (CSBM).An SBM is defined as a stool not induced by rescue medication, whereas a CSBM is defined as an SBM associated with a sensation of complete evacuation. Summary of Protocol Amendments: * Original Protocol: 06 January 2020 * Amendment 1: 30 July 2020 (Reason: To respond Health Authority requests) * Amendment 2: 05 March 2021 (Reason: Sponsor decided to amend the protocol. Key changes: inclusion/exclusion criteria, criteria for Discountinuation from study/Discontinuation from Study Medication, adding the instruction for evaluating and managing diarrhea AEs. )
Interventions
DRUGPradigastat Tablets 20mg
20mg, once daily, oral administration
DRUGPradigastat Tablets 40mg
40mg, once daily, oral administration
DRUGPradigastat Tablets 20mg matching Placebo
once daily, oral administration
DRUGPradigastat Tablets 40mg matching Placebo
once daily, oral administration
Sponsors
Covance
Anji Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double blind, placebo-controlled
Intervention model description
Randomized, double-blind and placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained before any assessment is performed. 2. Male and female patients aged 18 to 70 years of age, inclusive. 3. Patients with FC as defined by the ROME IV diagnostic criteria for FC. Diagnostic criteria for FC\*: * Must include 2 or more of the following: 1. Straining during more than one-fourth (25%) of defecations 2. Lumpy or hard stools (Bristol Stool Form Scale 1 or 2) more than one-fourth (25%) of defecations 3. Sensation of incomplete evacuation more than one-fourth (25%) of defecations 4. Sensation of anorectal obstruction/blockage more than one-fourth (25%) of defecations 5. Manual maneuvers to facilitate more than one-fourth (25%) of defecations (such as digital evacuation, or support of the pelvic floor) 6. Fewer than 3 SBMs per week * Loose stools are rarely present without the use of laxatives * Insufficient criteria for irritable bowel syndrome (IBS). \*Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. 4. Patient has less than 3 SBMs/week within 2 weeks prior to the Screening Visit. 5. Patient has completed a colonoscopy with no clinically significant findings which meet other
Exclusion criteria
within 12 months prior to Screening or at the Screening Visit. 6. Patient must agree that after the Visit 2 (Run-in Visit) they will discontinue any prohibited medications, laxatives (prescription and over-the-counter), supplemental fibers, or traditional medicine taken for abdominal symptoms or constipation as defined per protocol except the rescue medication, provided by the study site and following the Investigator's instructions for its use. Patient should not take rescue medication (bisacodyl) on the calendar day before and the calendar day of the start of the Treatment Period (Visit 3). If the wash-out criteria are not achieved on Visit 3, the Visit could be postponed once. 7. Patient must agree to use and comply with the diet guidance provided in applicable Chronic Constipation Treatment Guideline starting after the Screening Visit and during the study until End of Study. 8. Ability of patient to swallow tablets. 9. A co-operative attitude and ability to perform all study related procedures and to correctly use the diary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of pradigastat in changing the weekly spontaneous bowel movement (SBM) number compared with placebo in patients with functional constipation (FC) | Week 4 | Number change from baseline in the weekly SBM at Week 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of pradigastat in changing the weekly complete spontaneous bowel movement (CSBM) number compared with placebo in patients with FC | Week 4 | Number change from baseline in the weekly CSBM at Week 4 |
| Safety assessed by incidence of Adverse Events | Each visit through Week 4 | Safety assessed by incidence of Adverse Events |
| Efficacy of pradigastat in changing the responder rate compared with placebo in patients with FC | From baseline to every week until Week 4 | Weekly response rate for SBM |
| Change in weekly score for overall assessment of constipation symptoms and accompanied GI symptoms | From baseline to every week until Week 4 | Change in weekly score for overall assessment of constipation symptoms and accompanied GI symptoms (Weekly score includes 10 questions with the range of the total score from 10 to 68, and lower scores mean a better outcome.) |
| Trough pradigastat plasma concentrations | Week 1 and Week 4 | Mean plasma pradigastat concentration |
Countries
China, United States
Outcome results
None listed