Trial of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation
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Purpose
The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with irritable bowel syndrome with constipation (IBS-C).
The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder.
| Condition | Intervention | Phase |
|---|---|---|
|
Irritable Bowel Syndrome Characterized by Constipation |
Drug: Linaclotide 290 micrograms Drug: Matching placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks Followed by a 4-Week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With Constipation |
- Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
A patient is considered to be an APC responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs, experienced an increase of at least 1 CSBM from baseline, and experienced a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week.
The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP.
A CSBM is defined as a spontaneous bowel movement, associated with a sense of complete evacuation.
- Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week.
A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation.
An SBM was 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.
- Abdominal Pain Responder, 9 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week.
The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
- Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
A patient is considered an APC responder if, for at least 6 of the 12 weeks of the treatment, the patient experienced an increase of at least 1 Complete Spontaneous Bowel Movement (CSBM) from baseline and experienced a decrease of at least 30 percent in their Abdominal Pain (AP)score during a particular week.
The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP.
A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation.
- 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]The number of CSBMs per week.
- 12-Week Spontaneous Bowl Movement (SBM) Frequency Rate [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]The number of Spontaneous Bowl Movements experienced per week.
- 12-Week Stool Consistency [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7.
- = separate hard lumps like nuts [difficult to pass]
- = sausage shaped but lumpy
- = like a sausage but with cracks on surface
- = like a sausage or snake, smooth and soft
- = soft blobs with clear-cut edges [passed easily]
- = fluffy pieces with ragged edges, a mushy stool
- = watery, no solid pieces [entirely liquid]).
- 12-Week Severity of Straining [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]Straining is measured on a 5-point scale where a value of 1 is "not at all" and a value of 5 is "an extreme amount.
- 12-Week Change in Abdominal Pain Score [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
- 12-Week Change in Abdominal Discomfort [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]Abdominal Discomfort is measured on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe."
- 12-Week Change in Bloating [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]Bloating was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".
- Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.
- Abdominal Pain Responder for 6 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
A patient is considered to be an abdominal pain responder if, for at least 6 out of the 12 weeks of the treatment period, they experienced a decrease of 30 percent or more in the abdominal pain score from baseline.
The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
- 12-Week Percent of Abdominal Pain-free (APF) Days [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst
Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
| Enrollment: | 803 |
| Study Start Date: | July 2009 |
| Study Completion Date: | August 2010 |
| Primary Completion Date: | July 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Linaclotide
Linaclotide 290 micrograms
|
Drug: Linaclotide 290 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
|
|
Placebo Comparator: Placebo
Matching placebo
|
Drug: Matching placebo
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patient meets protocol criteria for IBS: reports abdominal discomfort or pain that has two or more of the following three features:
- Relieved with defecation
- Onset associated with a change in frequency of stool
- Onset associated with a change in form (appearance) of stool
- Patient reports < 3 bowel movements (BMs) per week (in the absence of any laxative, suppository, or enema use during the preceding 24 hours) and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during > 25% of BMs
- Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests (some patients may require a colonoscopy per American Gastroenterological Association (AGA) guidelines)
- Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting of BM habits and IBS symptoms
Exclusion Criteria:
- Patient has history of loose or watery stools for >25% of BMs
- Patient has a structural abnormality of the gastrointestinal (GI) tract or a history of a disease or condition that can affect GI motility
- Patient has any protocol-excluded or clinically significant medical or surgical history or concomitant medication use that could confound the study assessments
Contacts and Locations
Show 118 Study Locations| Study Director: | Paul F.C. Eng, PhD | Forest Research Institute, a subsidiary of Forest Laboratories Inc. |
More Information
No publications provided by Forest Laboratories
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Forest Laboratories |
| ClinicalTrials.gov Identifier: | NCT00948818 History of Changes |
| Other Study ID Numbers: | LIN-MD-31 |
| Study First Received: | July 28, 2009 |
| Results First Received: | September 28, 2012 |
| Last Updated: | December 19, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Forest Laboratories:
|
Irritable Bowel Syndrome Constipation Linaclotide |
Additional relevant MeSH terms:
|
Constipation Irritable Bowel Syndrome Signs and Symptoms, Digestive Signs and Symptoms Colonic Diseases, Functional |
Colonic Diseases Intestinal Diseases Gastrointestinal Diseases Digestive System Diseases |
ClinicalTrials.gov processed this record on May 19, 2013