Dose-ranging Study to Assess Safety and Efficacy of SP-333 for the Treatment of Opioid-induced Constipation (OIC) (OIC)

A Randomized, 4-Week, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Safety and Efficacy of SP-333 for the Treatment of Opioid-induced Constipation (OIC) in Patients With Non-malignant Chronic Pain Receiving Opioid Therapy

The purpose of this study is to evaluate the safety and efficacy of a range of oral SP-333 doses for the treatment of opioid-induced constipation (OIC) in adults with non-cancer pain taking opioids.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: Placebo; Drug: SP-333 1 mg; Drug: SP-333 3 mg; Drug: SP-333 6 mg

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Synergy Research Site
    • Mobile, Alabama, United States, 36608
      • Synergy Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Synergy Research Site
  • California
    • Artesia, California, United States, 90701
      • Synergy Research Site
    • Laguna Hills, California, United States, 92653
      • Synergy Research Site
    • Oceanside, California, United States, 92056
      • Synergy Research Site
    • Sacramento, California, United States, 95831
      • Synergy Research Site
    • San Diego, California, United States, 92103
      • Synergy Research Site
    • San Diego, California, United States, 92108
      • Synergy Research Site
    • San Francisco, California, United States, 94103
      • Synergy Research Site
  • Florida
    • Hialeah, Florida, United States, 33012
      • Synergy Research Site
    • Miami, Florida, United States, 33173
      • Synergy Research Site
    • Miami Beach, Florida, United States, 33140
      • Synergy Research Site
    • Plant City, Florida, United States, 33563
      • Synergy Research Site
    • Plantation, Florida, United States, 33317
      • Synergy Research Site
    • Port Orange, Florida, United States, 32129
      • Synergy Research Site
    • Sarasota, Florida, United States, 34239
      • Synergy Research Site
    • West Palm Beach, Florida, United States, 33409
      • Synergy Research Site
    • Winter Haven, Florida, United States, 33880
      • Synergy Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Synergy Research Site
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • Synergy Research Site
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Synergy Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Synergy Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Synergy Research Site
  • New York
    • Great Neck, New York, United States, 11023
      • Synergy Research Site
    • New York, New York, United States, 10016
      • Synergy Research Site
  • North Carolina
    • Concord, North Carolina, United States, 28025
      • Synergy Research Site
    • Greensboro, North Carolina, United States, 27403
      • Synergy Research Site
    • Salisbury, North Carolina, United States, 28144
      • Synergy Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Synergy Research Site
  • Ohio
    • Dayton, Ohio, United States, 45424
      • Synergy Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Synergy Research Site
    • Oklahoma City, Oklahoma, United States, 73101
      • Synergy Research Site
    • Oklahoma City, Oklahoma, United States, 73119
      • Synergy Research Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Synergy Research Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Synergy Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Synergy Research Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Synergy Research Site
    • Dallas, Texas, United States, 75231
      • Synergy Research Site
    • Dallas, Texas, United States, 75218
      • Synergy Research Site
    • Houston, Texas, United States, 77081
      • Synergy Research Site
    • San Antonio, Texas, United States, 78209
      • Synergy Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be receiving chronic, stable opioid therapy to treat non-malignant pain for at least 3 months prior to screening
• Must have active OIC at screening
• Active OIC must be confirmed during baseline screening bowel habit and symptom diary
• Must be on stable diet

Exclusion Criteria:

• Has history of chronic therapy for chronic constipation prior to start of opioid therapy, or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation (i.e., mechanical obstruction or pseudo-obstruction)
• Use of medications that might affect bowel movement frequency or constipation-related symptoms (e.g., prokinetics, anti-diarrheal agents, laxatives other than study-defined rescue laxative)
• Has history of or current cancer (other than basal cell or squamous cell carcinoma of the skin) unless the malignancy has been in complete remission without maintenance chemotherapy for at least 5 years
• Unstable thyroid disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SP-333 1 mg; 1 mg SP-333 orally once daily for 4-week Treatment Period	Drug: SP-333 1 mg; Tablet
Experimental: SP-333 3 mg; 3 mg SP-333 orally once daily for 4-week Treatment Period	Drug: SP-333 3 mg; Tablet
Experimental: SP-333 6 mg; 6 mg SP-333 orally once daily for 4-week Treatment Period	Drug: SP-333 6 mg; Tablet
Placebo Comparator: Placebo; Placebo orally once daily for 4-week Treatment Period	Drug: Placebo; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the number of spontaneous bowel movements during Week 4 of the 4-week treatment period	Compare SP-333 (1, 3 & 6 mg) with placebo in the treatment of OIC as measured by the change from baseline in the number of spontaneous bowel movements during Week 4 of the 4-week treatment period	4 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess safety and tolerability of SP-333 in the treatment of non-malignant OIC	Compare the safety and tolerability of SP-333 (1, 3 & 6 mg) with placebo as measured by rates of adverse events, clinical laboratory abnormalities and significant changes in vital signs and ECGs.	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate stool consistency over the 4-week Treatment Period	Compare SP-333 (1, 3 & 6 mg) with placebo in rates of change from baseline in stool consistency over the 4 weeks of treatment.	4 weeks
To evaluate constipation-related symptoms over the 4-week Treatment Period	Compare SP-333 (1, 3 & 6 mg) with placebo in rates of change from baseline in constipation-related symptoms over the 4 weeks of treatment.	4 weeks
To evaluate bowel movement frequency responder rates [Complete Spontaneous Bowel Movements (CSBMs) and Spontaneous Bowel Movements (SBMs)] over the 4-week Treatment Period.	Compare SP-333 (1, 3 & 6 mg) with placebo in rates of change from baseline for bowel movement frequency responder rates [Complete Spontaneous Bowel Movements (CSBMs) and Spontaneous Bowel Movements (SBMs)] over the 4 weeks of treatment.	4 weeks

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Study Director: Renata Tenenbaum, Synergy Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: October 29, 2013
• First Submitted That Met QC Criteria: November 6, 2013
• First Posted (Estimate): November 13, 2013

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Constipation; Pain; Opioid; GC C Agonist
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Dolcanatide
• Other Study ID Numbers: SP333201-01