Trial of Linaclotide in Patients With Chronic Idiopathic Constipation
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02291679 |
|
Recruitment Status :
Completed
First Posted : November 14, 2014
Results First Posted : May 19, 2017
Last Update Posted : June 15, 2017
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Idiopathic Constipation | Drug: Linaclotide Drug: Matching Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1223 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide (72 ug or 145 ug) Administered Orally for 12 Weeks to Patients With Chronic Idiopathic Constipation |
| Study Start Date : | October 2014 |
| Actual Primary Completion Date : | August 2015 |
| Actual Study Completion Date : | August 2015 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 72 μg linaclotide
72 μg oral linaclotide, once daily for 12 weeks
|
Drug: Linaclotide
Other Names:
|
|
Experimental: 145 μg linaclotide
145 μg oral linaclotide, once daily for 12 weeks
|
Drug: Linaclotide
Other Names:
|
|
Placebo Comparator: Placebo
matching placebo, once daily for 12 weeks
|
Drug: Matching Placebo |
- Percentage of 12-Week CSBM Overall Responders [ Time Frame: Week 12 ]
A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥ 4 IVRS calls for the specified week.
A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a bowel movement BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Change From Baseline in 12-Week CSBM Frequency Rate [ Time Frame: Baseline, Week 1 to Week 12 ]A participant's 12-week CSBM Frequency Rate is the CSBM rate (CSBMs/week) calculated over the 12 weeks of the Treatment Period. A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Change From Baseline in 12-Week SBM Frequency Rate [ Time Frame: Baseline, Week 1 to Week 12 ]A participant's 12-week SBM Frequency Rate is the SBM rate (SBMs/week) calculated over the 12-weeks of the Treatment Period. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Change From Baseline in 12-Week Stool Consistency Score [ Time Frame: Baseline, Week 1 to Week 12 ]Stool consistency was measured daily using the 7-point ordinal Bristol Stool Form Scale (BSFS; 1 = separate hard lumps like nuts [difficult to pass]; 2 = sausage shaped but lumpy; 3 = like a sausage but with cracks on surface; 4 = like a sausage or snake, smooth and soft; 5 = soft blobs with clear-cut edges [passed easily]; 6 = fluffy pieces with ragged edges, a mushy stool; 7 = watery, no solid pieces [entirely liquid]). The participant's BSFS score for the Treatment Period is the average of the non-missing BSFS scores from the SBMs reported by the participant during the 12-week Treatment Period.
- Change From Baseline in 12-Week Straining Score [ Time Frame: Baseline, Week 1 to Week 12 ]Straining was measured daily using a 5-point ordinal scale (1 = not at all; 2 = a little bit; 3 = a moderate amount; 4 = a great deal; 5 = an extreme amount). The participant's straining score for the Treatment Period is the average of the non-missing straining scores from the SBMs reported by the participant during the 12-week Treatment Period.
- Percentage of 12-Week CSBM Overall Responders (>1 SBM/Week Subpopulation) [ Time Frame: Week 12 ]
A 12-week CSBM Overall Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥4 IVRS calls for the specified week.
A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Percentage of Month 1 CSBM Responders [ Time Frame: Month 1 ]
A Month 1 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 1 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week.
A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Percentage of Month 2 CSBM Responders [ Time Frame: Month 2 ]
A Month 2 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 2 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week.
A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Percentage of Month 3 CSBM Responders [ Time Frame: Month 3 ]
A Month 3 CSBM Responder is a participant who is a CSBM weekly responder for at least 3 of the 4 weeks of Month 3 of the Treatment Period. A CSBM weekly responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline based on a minimum of 4 complete IVRS calls for that week.
A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
- Change From Baseline in 12-Week Abdominal Bloating [ Time Frame: Baseline, Week 1 to Week 12 ]Abdominal bloating was measured daily using an 11-point NRS (0 = none; 10 = very severe). The participant's abdominal bloating score for the Treatment Period is the average of the non-missing daily participant assessments of abdominal bloating scores reported during the 12-week Treatment Period.
- Change From Baseline in 12-Week Abdominal Discomfort [ Time Frame: Baseline, Week 1 to Week 12 ]Abdominal discomfort was measured daily using an 11-point NRS (0 = none; 10 = very severe). The participant's abdominal discomfort score for the Treatment Period is the average of the non-missing daily participant assessments of abdominal discomfort scores reported during the 12-week Treatment Period.
- Percentage of 12-Week CSBM Overall Sustained Responders [ Time Frame: Week 12 ]
A 12-week CSBM Overall Sustained Responder is a participant who was a CSBM Weekly Responder for at least 9 of the 12 weeks of the Treatment Period, including ≥ 3 of the last 4 weeks. A CSBM Weekly Responder is a participant who had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline, and completed ≥ 4 IVRS calls for the specified week.
A CSBM is defined as an SBM that is associated with a sense of complete evacuation. An SBM is defined as a BM that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patient has completed a colonoscopy if one is needed according to the American Gastroenterological Association (AGA) criteria, with no clinically significant findings
- Patient has no clinically significant findings on a physical examination and clinical laboratory tests
- Patient meets protocol criteria for CIC: reports < 3 bowel movements (BMs) per week and reports one or more of the following during ≥ 25% of BMs: straining, lumpy or hard stools, sensation of incomplete evacuation during the 3 months before the diagnosis with the onset at least 6 months before the diagnosis
- Patient is compliant with daily interactive voice response system (IVRS) calls
- Patient reports an average of < 3 complete spontaneous BMs (CSBMs) and ≤ 6 SBMs per week by the IVRS over the 14 calendar days before the Randomization Visit and the calendar day of Randomization.
Exclusion Criteria:
- Patient has history of loose or watery stools
- Patient has symptoms of or been diagnosed with irritable bowel syndrome (IBS)
- Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
- Patient has any protocol-excluded or clinically significant medical or surgical history that could confound the study assessments
- Patient has Bristol Stool Form Scale score of 7 during Pretreatment period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02291679
Show 95 study locations
| Study Chair: | Bernard J Lavins, MD | Ironwood Pharmaceuticals, Inc. |
| Responsible Party: | Ironwood Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT02291679 |
| Other Study ID Numbers: |
MCP-103-309 |
| First Posted: | November 14, 2014 Key Record Dates |
| Results First Posted: | May 19, 2017 |
| Last Update Posted: | June 15, 2017 |
| Last Verified: | May 2017 |
|
Constipation Signs and Symptoms, Digestive Linaclotide Guanylyl Cyclase C Agonists |
Enzyme Activators Molecular Mechanisms of Pharmacological Action Gastrointestinal Agents |