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Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

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ClinicalTrials.gov Identifier: NCT02270983
Recruitment Status : Completed
First Posted : October 22, 2014
Results First Posted : April 8, 2019
Last Update Posted : April 8, 2019
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Forest Laboratories

Study Description
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Brief Summary:

The purpose of this study was to evaluate the safety and efficacy of linaclotide for the treatment of opioid-induced constipation (OIC), in adults receiving stable opioid treatment for chronic non-cancer pain that has been present for a minimum of 3 months.

This study included up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Patients meeting the entry criteria were randomized to 1 of 2 doses of linaclotide or placebo once per day for 8 weeks. This 8-week study assessed the effects of linaclotide on bowel movement frequency, as well as other bowel symptoms of OIC.


Condition or disease Intervention/treatment Phase
Opioid-Induced Constipation Drug: Linaclotide 145 micrograms Drug: Linaclotide 290 micrograms Drug: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 254 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered Orally for 8 Weeks to Adult Outpatients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain
Actual Study Start Date : October 31, 2014
Actual Primary Completion Date : August 31, 2015
Actual Study Completion Date : October 31, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Constipation

Arms and Interventions
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Arm Intervention/treatment
Experimental: Linaclotide 145 micrograms
Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.
 Drug: Linaclotide 145 micrograms
Other Name: Linzess
Experimental: Linaclotide 290 micrograms
Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.
 Drug: Linaclotide 290 micrograms
Other Name: Linzess
Experimental: Placebo
Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.
 Drug: Placebo
Matching placebo


Outcome Measures
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Primary Outcome Measures :
  1. Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week) [ Time Frame: Baseline (Week 0) to Week 8 ]
    Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.


Secondary Outcome Measures :
  1. Time to First SBM After the First Dose of Investigational Product [ Time Frame: Baseline (Day 0) up to 8 weeks ]
    The median time to the first SBM after the first dose of investigational product

  2. Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria [ Time Frame: 8-week treatment period ]
    A 6/8 Week SBM 3 + 1 responder was a participant who met the weekly SBM 3 + 1 responder criteria for at least 6 out of the 8 weeks of the Treatment Period. For each week in the Treatment Period, a weekly SBM 3 + 1 responder was a patient who had an SBM weekly rate ≥ 3 and an increase ≥ 1 in the SBM weekly rate from baseline for that week.

  3. Change From Baseline in 8-Week Stool Consistency [ Time Frame: Baseline (Week 0) to Week 8 ]

    Stool Consistency was assessed using the 7-Point Bristol Stool Form Scale:

    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
    7. = watery, no solid pieces (entirely liquid)

  4. Change From Baseline in 8-Week Straining [ Time Frame: Baseline (Week 0) to Week 8 ]
    Straining was measured on a 5-point ordinal scale where a value of 1 is "not at all" and a value of 5 is "an extreme amount."

  5. Change From Baseline in 8-Week Abdominal Bloating [ Time Frame: Baseline (Week 0) to Week 8 ]
    Abdominal bloating was collected daily via IVRS calls and measured using an 11-point numerical rating scale, where 0 represents no abdominal bloating and 10 represents very severe abdominal bloating.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has chronic non-cancer pain that has been present for a minimum of 3 months
  • Patient has been receiving a stable oral dose of a full-opioid agonist for at least 4 days per week during the 8 consecutive weeks

  • Patient meets protocol criteria for Opioid-Induced Constipation (OIC): < 3 spontaneous bowel movements (SBMs) per week and reports one of the following symptoms for at least 4 weeks:

    1. Straining during > 25% of BMs
    2. Lumpy or hard stools during > 25% of BMs
    3. Sensation of incomplete evacuation during > 25% of BMs
  • Patient meets the colonoscopy requirements defined by the American Gastroenterological Association guidelines
  • Patient has successfully completed protocol procedures (with no clinically significant findings)
  • Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting
  • Patient has a total of < 6 SBMs in IVRS during the 14 days before and up to the time of Randomization
  • Patient has adequate relief and well-controlled pain with current dose of opioid

Exclusion Criteria:

  • Patient has been using opioids for abdominal pain
  • Patient has symptoms of or been diagnosed with chronic constipation or chronic idiopathic constipation prior to initiation of opioid treatment
  • Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS) prior to initiation of opioid treatment
  • Patient has a history of loose or watery stools for > 25% of BMs during the 3 months before the Screening in the absence of laxatives, suppositories, or enemas
  • 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 would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments
Contacts and Locations
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Information from the National Library of Medicine

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): NCT02270983


Locations
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Sponsors and Collaborators
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
Investigators
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Study Director: Patricia D'Astoli, RN Forest Laboratories, LLC, an Allergan Affiliate
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT02270983    
Other Study ID Numbers: LIN-MD-40
First Posted: October 22, 2014    Key Record Dates
Results First Posted: April 8, 2019
Last Update Posted: April 8, 2019
Last Verified: April 2019
Keywords provided by Forest Laboratories:
Opioid-Induced Constipation
Linaclotide
Linzess
Additional relevant MeSH terms:
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Constipation
Signs and Symptoms, Digestive
Linaclotide
Guanylyl Cyclase C Agonists
 Enzyme Activators
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents