E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic idiopathic constipation |
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E.1.1.1 | Medical condition in easily understood language |
Chronic idiopathic constipation is a condition of infrequent bowel movements and difficult passage of stools which does not go away |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072118 |
E.1.2 | Term | Chronic idiopathic constipation |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy, as determined by overall complete spontaneous bowel movement (CSBM) response, of repeated daily doses of 5 mg and 10 mg elobixibat for the first 12 weeks in patients with chronic idiopathic constipation (CIC). |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the efficacy of repeated daily doses of 5 mg and 10 mg elobixibat on other bowel movement (BM) parameters, CIC symptoms, constipation affected work productivity and activity impairment, health care resource use, and patient assessments of effectiveness based on selected quality of life measurements.
To assess the safety and tolerability of repeated daily doses of 5 mg and 10 mg elobixibat for 26 weeks in patients with CIC.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.The patient reports having understood and has signed the Informed Consent Form (ICF) and is willing to comply with all trial visits and assessments 2.The patient is a male or female ≥18 years of age 3.The patient has a body mass index (BMI) ≥18.5 but <35.0 4.The patient is ambulatory and community dwelling 5.The patient meets modified Rome III criteria: reports <3 spontaneous BM (SBM; defined as a BM occurring in the absence of any laxative intake in the form of a tablet, a suppository or an enema during the preceding 24 hours) per week and reports one or more of the following symptoms for the last 3 months with symptom onset at least 6 months before the Screening Visit or before starting chronic therapy with any laxative e.g. tegaserod, lubiprostone, linaclotide, polyethylene glycol 3350, prucalopride: a.Straining during at least 25% of defecations b.Lumpy or hard stools during at least 25% of defecations c.Sensation of incomplete evacuation during at least 25% of defecations 6.The patient reports an average of <3 complete SBMs (CSBMs; defined as an SBM associated with a sense of complete evacuation) and ≤6 SBMs per week by the PDA during the 14 full days before the randomisation visit 7.An initial colonoscopy is required if this is recommended according to national guidelines. If no national guidelines are available, a colonoscopy is performed if recommended according to modified American College of Gastroenterology Guidelines for Colorectal Cancer Screening 8.The patient is compliant with PDA by having adequately responded to the PDA questions on ≥10 of the most recent 14 full days before randomisation vist, recording BMs, stool consistency, and gastrointestinal (GI) symptoms (pain, straining, and discomfort) 9.The patient agrees to refrain from making any new, major life-style changes that may affect CIC symptoms (i.e., starting a new diet, changing an exercise plan) from the time of signing the ICF through to the last trial visit.
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E.4 | Principal exclusion criteria |
1.The patient reports loose (mushy) or watery stools (Bristol Stool Form Scale [BSFS] score of 6 or 7) in the absence of any laxative intake in the form of a tablet, a suppository or an enema, or prohibited medicine for >25% of BMs during the 12 weeks prior to the Screening Visit 2.The patient reports a BSFS of 6 or 7 on any day during the Pretreatment Period, unless this occurred within 24 hours of having taken rescue medication. 3.The patient has irritable bowel syndrome (IBS) with pain/discomfort as predominant symptoms as defined by the Rome III criteria: reports abdominal discomfort or pain that has two or more of the following three features the last 3 months with symptom onset at least 6 months before the Screening Visit: a.Improvement with defecation b.Onset associated with a change in frequency of stool c.Onset associated with a change in form (appearance) of stool 4.The patient has a structural abnormality of the GI tract or a disease or condition that can affect GI motility. 5. The patient has a history of any gastro-intestinal disease not considered to be CIC.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the overall CSBM Response, where a responder is 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 first 12 weeks of the 26-week Treatment Period, including at least 3 weeks in Weeks 9-12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Occurrence of a CSBM within 24 hours of treatment initiation •Change from Baseline in weekly frequency of spontaneous bowel movements (SBMs) for the overall first 12 weeks of the 26-week Treatment Period •Change from Baseline in weekly stool consistency of SBMs for the overall first 12 weeks of the 26-week Treatment Period •Total PAC-QOL score responder at Week 12 •Change from Baseline in weekly degree of straining of SBMs for the overall first 12 weeks of the 26-week Treatment Period •Change from Baseline in weekly abdominal bloating score for the overall first 12 weeks of the 26-week Treatment Period •Change from Baseline in weekly abdominal discomfort score for the overall first 12 weeks of the 26-week Treatment Period •Safety: adverse events (AEs), clinical safety laboratory variables (haematology, clinical chemistry, urinalysis), ECGs, vital signs, and concomitant medications |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Brazil |
Czech Republic |
Germany |
Israel |
Poland |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |