A study to establish whether Linaclotide is effective in reducing abominal distension in men and women with constipation predominant IBS
- Conditions
- Irritable Bowel Syndrome with ConstipationMedDRA version: 20.0Level: LLTClassification code 10066868Term: Constipation predominant irritable bowel syndromeSystem Organ Class: 100000004856Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
- Registration Number
- EUCTR2016-000818-29-GB
- Lead Sponsor
- Ironwood Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1. Participant has provided written informed consent before participating in the study after being given a full description of the study and prior to any study-specific procedures being performed.
2. Participant is a male or non-pregnant, non-breastfeeding female, and is age 18 years or older (no upper age limit).
3. Female participants of childbearing potential must complete a urine pregnancy test with negative results at the Screening Visit (Visit 1) and again at the Randomisation Visit (Visit 4) prior to dosing.
4. Female participants who are pre-menopausal should be enrolled between days 7 and 21 of their menstrual cycle.
5. Sexually active female participants of childbearing potential must agree to use one of the following methods of contraception from the date that they sign the ICF until the end of study:
a. Hormonal contraception (i.e., oral contraceptive, contraceptive implant, or injectable hormonal contraceptive);
b. Intra-uterine device (IUD);
c. A barrier birth control (such as condoms or occlusive cap with spermicidal foam/gel/film/cream/suppository);
d. Surgical sterilisation (i.e., bilateral oophorectomy, hysterectomy, or tubal ligation);
e. Abstinence, when in the opinion of the Investigator, the participant’s occupation or lifestyle gives sufficient evidence that abstinence will be maintained throughout the study and for 1 month thereafter.
6. Participant meets Rome III criteria for IBS-C, as well as abdominal pain score (average of = 3 on 0-10 point numerical rating scale [NRS]), abdominal bloating score (average of = 5 on 0-10 point NRS), and abdominal girth measurement (AIP increase of > 4 cm) criteria during the Pretreatment Period.
7. Participant agrees to refrain from strenuous physical activity for 24 hours prior to each study visit.
8. Participant agrees to refrain from initiating any lifestyle or dietary changes.
9. Participant agrees to refrain from taking any probiotics from 14 days prior to enrolment in the study throughout the Treatment Period.
10. Participant is able to communicate well with the Investigator and to comply with the requirements for the entire study.
11. Participant has a body mass index (BMI) between 18.5 and 34.9 kg/m2 (bounds included) at the Screening Visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Participant reports loose (mushy) or watery stools (BSFS score of 6 or 7) in the absence of any laxative, suppository, enema, or prohibited medicine (as described in Appendix 1) for > 25% of BMs during the 12 weeks before the Screening Visit.
2. Participant has ever had a diagnosis of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or any other form of familial colorectal cancer, or inflammatory bowel disease.
3. Participant currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding, iron-deficiency anaemia or any unexplained anaemia, or weight loss) or systemic signs of infection or colitis.
4. Participant currently has active peptic ulcer disease (i.e., disease that is not adequately treated or stable with therapy).
5. Participant has a history of any chronic GI condition (e.g., diverticulitis) that can be associated with abdominal pain or discomfort.
6. Participant has CNS disease or any organic condition associated with constipation.
7. Participant has had surgery that meets any of the following criteria:
a. Has undergone any surgery within 6 months prior to the Screening Visit;
b. Has had previous abdominal surgery except appendectomy, cholecystectomy, or hysterectomy.
8. Participant has diabetes.
9. Participant reports using a Prohibited Medicine (excluding laxatives, suppositories, and enemas) during the Pretreatment Period or is not willing or able to abide by the restrictions regarding use of Prohibited Medicines defined in Appendix 1. (Note: the use of fibre, bulk laxatives, or stool softeners [such as docusate] is acceptable provided that the participant has been on a stable dose during the 30 days before the Screening Visit and plans to continue on
a stable dose throughout the study.)
10. Participant has taken commercially available linaclotide during the 30 days prior to the Screening Visit.
11. Participant is drinking alcohol above the recommended safe alcohol limit (< 21 units/week) or abusing drugs. In addition, participants will be asked to refrain from drinking alcohol for 24 hours before plethysmography recordings until belt removal.
12. Participant has lactose intolerance.
13. Participant has an acute or chronic condition that, in the Investigator’s opinion, would limit the participant’s ability to complete or participate in this clinical study.
14. Participant is involved in this study as an Investigator, sub-Investigator, study coordinator, other study staff, or Sponsor member.
15. Participant has a known or suspected mechanical gastrointestinal obstruction.
16. Participant has a history of hypersensitivity to linaclotide or to any of the excipients contained in the study drug (active or placebo).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the effect of linaclotide on abdominal girth in irritable bowel syndrome with constipation (IBS-C) participants with baseline symptoms of abdominal bloating and an increased abdominal girth.;Secondary Objective: Not applicable;Primary end point(s): Mean change from randomisation (Visit 4) to the end of the study (Visit 8) in abdominal girth (as measured by AUC) determined by 24-hour AIP between the linaclotide and placebo groups.;Timepoint(s) of evaluation of this end point: Data on abdominal girth will be downloaded and analysed from the data logger by a blinded member of the research team when participants return with the belt at the Randomisation, Day 15, and End of Treatment Visits.<br><br>Comparisons of the mean change in abdominal girth over 24 hours (as measured by AUC) will be made between the baseline and mid-study, and baseline and end-of-treatment assessments.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary efficacy assessments are the diary questions that determine the following:<br>• Daily participant assessment of abdominal pain, discomfort, bloating, and distension;<br>• Whether a BM is an SBM;<br>• Whether an SBM is a CSBM;<br>• Stool consistency (Bristol Stool Form Scale [BSFS]) with each BM.;Timepoint(s) of evaluation of this end point: To determine these secondary outcome measures, participants will be asked to complete paper daily diaries in the evening (or approximately the same time each day).