Clinical trial NCT01443403: A Study of Naldemedine (S-297995) for the Treatment of Opioid-Induced Constipation in Adults With Non-Malignant Chronic Pain Receiving Opioid Therapy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of S-297995 for the Treatment of Opioid-Induced Constipation in Subjects With Non-Malignant Chronic Pain Receiving Opioid Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid-induced Constipation
Keywords: Opioid Therapy
Non-Malignant Chronic Pain
Opioid-Induced Constipation
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2011-09-29
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine efficacy and safety of naldemedine for the treatment of opioid-induced constipation in adults with non-malignant chronic pain receiving opioid therapy for ≥ 3 months.


Eligibility criteria: Inclusion Criteria:

* Subjects aged 18 years or older at time of informed consent with non-malignant chronic pain experiencing opioid-induced constipation
* Subjects with \< 3 spontaneous bowel movements a week and experiencing bowel symptoms
* Subjects receiving chronic opioid therapy due to non-malignant pain for ≥ 3 months

Exclusion Criteria:

* Evidence of clinically significant gastrointestinal disease
* History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation
* Severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation

Primary outcomes:
measure: Change From Baseline to Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
timeFrame: Baseline (2 weeks prior to randomization) and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
Secondary outcomes:
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Spontaneous Bowel Movements Per Week
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Bowel Movements (BMs) Per Week
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Bowel Movements Per Week
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Bowel Movements (CBMs) Per Week
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Bowel Movements Per Week
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements (CSBMs) Per Week
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of Complete Spontaneous Bowel Movements Per Week
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Percentage of Participants With an SBM Response in the Last 2 Weeks of the Treatment Period
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Percentage of Participants With an SBM Response at Weeks 1, 2, 3 and 4
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Percentage of Participants With a CSBM Response in the Last 2 Weeks of the Treatment Period
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Percentage of Participants With a CSBM Response at Weeks 1, 2, 3, and 4
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With SBMs
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With SBMs
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of Days Per Week With CSBMs
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3 and 4 in Number of Days Per Week With CSBMs
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Time to the First Spontaneous Bowel Movement
timeFrame: 28 days
measure: Time to the First Complete Spontaneous Bowel Movement
timeFrame: 28 days
measure: Percentage of Participants With SBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
timeFrame: 4, 8, 12, and 24 hours
measure: Percentage of Participants With CSBMs Within 4, 8, 12, and 24 Hours After the Initial Administration of Study Drug
timeFrame: 4, 8, 12, and 24 hours
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week Rated as 3 or 4 on the Bristol Stool Scale
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in Number of SBMs Rated as 3 or 4 on the Bristol Stool Scale Per Week
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of SBMs Per Week With no Straining
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in the Number of SBMs Per Week Without Straining
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Number of False Start BMs Per Week
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Rescue Use of Laxative Agents Per Week
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Mean Rescue Laxative Use Per Week During the Treatment Period
timeFrame: Weeks 1 to 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Bloating
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Bloating
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in Abdominal Discomfort
timeFrame: Baseline and the last 2 weeks of treatment (Weeks 3 to 4 for participants who completed the 28-day treatment period)
measure: Change From Baseline to Weeks 1, 2, 3, and 4 in Abdominal Discomfort
timeFrame: Baseline and Weeks 1, 2, 3, and 4
measure: Subject Global Satisfaction at End of Treatment
timeFrame: Day 29, or at early termination
measure: Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
timeFrame: Day 1 and Day 28 predose and 1, 2, 4, 8, and 24 hours postdose
measure: Time to Maximum Concentration (Tmax) of Naldemedine and Metabolite Nor-S-297995
timeFrame: Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
measure: Area Under the Concentration-time Curve From Hour 0 to the Time Point of the Last Measurable Concentration Within the Dose Interval (AUC0-τ)
timeFrame: Day 1 and Day 28 predose and 1, 2 , 4, 8, and 24 hours postdose
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug through 28 days after the last dose of study treatment (up to 57 days).
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Shionogi Research Site
state: Arizona
city: Sun Lakes
country: United States
facility: Shionogi Research Site
state: Arizona
city: Little Rock
country: United States
facility: Shionogi Research Site
state: Arkansas
city: Anaheim
country: United States
facility: Shionogi Research Site
state: California
city: Fresno
country: United States
facility: Shionogi Research Site
state: California
city: Lincoln
country: United States
facility: Shionogi Research Site
state: California
city: Lomita
country: United States
facility: Shionogi Research Site
state: California
city: Denver
country: United States
facility: Shionogi Research Site
state: Colorado
city: Brandon
country: United States
facility: Shionogi Research Site
state: Florida
city: Kissimmee
country: United States
facility: Shionogi Research Site
state: Florida
city: New Port Richey
country: United States
facility: Shionogi Research Site
state: Florida
city: North Miami
country: United States
facility: Shionogi Research Site
state: Florida
city: Ocala
country: United States
facility: Shionogi Research Site
state: Florida
city: Orlando
country: United States
facility: Shionogi Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Shionogi Research Site
state: Florida
city: Port Orange
country: United States
facility: Shionogi Research Site
state: Florida
city: Sarasota
country: United States
facility: Shionogi Research Site
state: Florida
city: South Miami
country: United States
facility: Shionogi Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Shionogi Research Site
state: Florida
city: Atlanta
country: United States
facility: Shionogi Research Site
state: Georgia
city: Decatur
country: United States
facility: Shionogi Research Site
state: Georgia
city: Marietta
country: United States
facility: Shionogi Research Site
state: Georgia
city: Evansville
country: United States
facility: Shionogi Research Site
state: Indiana
city: Lexington
country: United States
facility: Shionogi Research Site
state: Kentucky
city: Shreveport
country: United States
facility: Shionogi Research Site
state: Louisiana
city: Owings Mills
country: United States
facility: Shionogi Research Site
state: Maryland
city: Watertown
country: United States
facility: Shionogi Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Shionogi Research Site
state: Massachusetts
city: Traverse City
country: United States
facility: Shionogi Research Site
state: Michigan
city: Edina
country: United States
facility: Shionogi Research Site
state: Minnesota
city: Las Vegas
country: United States
facility: Shionogi Research Site
state: Nevada
city: Newington
country: United States
facility: Shionogi Research Site
state: New Hampshire
city: Berlin
country: United States
facility: Shionogi Research Site
state: New Jersey
city: Willingboro
country: United States
facility: Shionogi Research Site
state: New Jersey
city: Hartsdale
country: United States
facility: Shionogi Research Site
state: New York
city: North Syracuse
country: United States
facility: Shionogi Research Site
state: New York
city: Williamsville
country: United States
facility: Shionogi Research Site
state: New York
city: Wilmington
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Canton
country: United States
facility: Shionogi Research Site
state: Ohio
city: Columbus
country: United States
facility: Shionogi Research Site
state: Ohio
city: Perrysburg
country: United States
facility: Shionogi Research Site
state: Ohio
city: Eugene
country: United States
facility: Shionogi Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Shionogi Research Site
state: Pennsylvania
city: Greer
country: United States
facility: Shionogi Research Site
state: South Carolina
city: Austin
country: United States
facility: Shionogi Research Site
state: Texas
city: Dallas
country: United States
facility: Shionogi Research Site
state: Texas
city: Orem
country: United States
facility: Shionogi Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Shionogi Research Site
state: Utah
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References:
citation: Webster LR, Yamada T, Arjona Ferreira JC. A Phase 2b, Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain. Pain Med. 2017 Dec 1;18(12):2350-2360. doi: 10.1093/pm/pnw325.