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
Condition: Opioid-Induced Constipation
MeSH terms: Constipation; Opioid-Induced Constipation
Intervention: Linaclotide 145 micrograms; Linaclotide 290 micrograms; Placebo
Intervention description: Matching placebo
Intervention MeSH terms: Linaclotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 254.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Opioid-Induced Constipation; Linaclotide; Linzess

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.
    

Eligibility 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