Clinical trial NCT01993940: Efficacy and Safety of Naldemedine in Treating Opioid-induced Constipation
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Naldemedine in the Treatment of Opioid-induced Constipation in Subjects With Non-malignant Chronic Pain Receiving Opioid Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid-induced Constipation
Keywords: Opioid-induced Constipation
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 553
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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 evaluate the efficacy and safety of naldemedine in the treatment of opioid-induced constipation (OIC) in adults with non-malignant chronic pain who are not using laxatives.


Eligibility criteria: Inclusion Criteria:

* Subjects aged 18 to 80 years inclusive at the time of informed consent
* Subjects must have non-malignant chronic pain treated with opioids and must have opioid-induced constipation (OIC)
* Subjects must be treated with a stable opioid regimen at a total daily dose on average of ≥ 30 mg equivalents of oral morphine sulfate
* Subjects must not be currently using laxatives or must be willing to discontinue laxative use at Screening and must be willing to use only the rescue laxatives provided throughout the study duration
* Subjects must meet opioid-induced constipation criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary

Exclusion Criteria:

* Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
* Evidence of active medical diseases affecting bowel transit
* History or presence of pelvic disorders that may be a cause of constipation
* Surgery (except for minor procedures) within 60 days of Screening
* 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 (e.g., mechanical GI obstruction)
* Subjects who have never taken laxatives for the treatment of OIC
* History of active treatment for cancer within the last 2 years (except for basal cell or squamous cell carcinoma of the skin that have been successfully resected) or tamoxifen \[Nolvadex®\] and raloxifene \[Evista®\] when being used for prevention of breast cancer
* Current use of any prohibited medication including opioid antagonists, partial agonists, or mixed agonists/antagonists

Primary outcomes:
measure: Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response
timeFrame: 12-week treatment period
Secondary outcomes:
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week
timeFrame: Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)
measure: Change From Baseline to Week 1 in the Number of Spontaneous Bowel Movements Per Week
timeFrame: Baseline and Week 1
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements Per Week
timeFrame: Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)
measure: Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements With No Straining Per Week
timeFrame: Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Shionogi Research Site
state: Alabama
city: Homewood
country: United States
facility: Shionogi Research Site
state: Alabama
city: Goodyear
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: Buena Park
country: United States
facility: Shionogi Research Site
state: California
city: Corona
country: United States
facility: Shionogi Research Site
state: California
city: Gold River
country: United States
facility: Shionogi Research Site
state: California
city: Los Angeles
country: United States
facility: Shionogi Research Site
state: California
city: Modesto
country: United States
facility: Shionogi Research Site
state: California
city: Pasadena
country: United States
facility: Shionogi Research Site
state: California
city: Coral Gables
country: United States
facility: Shionogi Research Site
state: Florida
city: Hialeah
country: United States
facility: Shionogi Research Site
state: Florida
city: Jacksonville
country: United States
facility: Shionogi Research Site
state: Florida
city: Miami Beach
country: United States
facility: Shionogi Research Site
state: Florida
city: Miami
country: United States
facility: Shionogi Research Site
state: Florida
city: Plantation
country: United States
facility: Shionogi Research Site
state: Florida
city: Columbus
country: United States
facility: Shionogi Research Site
state: Georgia
city: Evansville
country: United States
facility: Shionogi Research Site
state: Indiana
city: Indianapolis
country: United States
facility: Shionogi Research Site
state: Indiana
city: West Des Moines
country: United States
facility: Shionogi Research Site
state: Iowa
city: Edgewood
country: United States
facility: Shionogi Research Site
state: Kentucky
city: Crowley
country: United States
facility: Shionogi Research Site
state: Louisiana
city: Kalamazoo
country: United States
facility: Shionogi Research Site
state: Michigan
city: Traverse City
country: United States
facility: Shionogi Research Site
state: Michigan
city: Butte
country: United States
facility: Shionogi Research Site
state: Montana
city: Omaha
country: United States
facility: Shionogi Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Shionogi Research Site
state: Nevada
city: Omaha
country: United States
facility: Shionogi Research Site
state: Nevada
city: Albuquerque
country: United States
facility: Shionogi Research Site
state: New Mexico
city: Hopewell Junction
country: United States
facility: Shionogi Research Site
state: New York
city: Mooresville
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Dayton
country: United States
facility: Shionogi Research Site
state: Ohio
city: Marion
country: United States
facility: Shionogi Research Site
state: Ohio
city: Media
country: United States
facility: Shionogi Research Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: Shionogi Research Site
state: South Carolina
city: Knoxville
country: United States
facility: Shionogi Research Site
state: Tennessee
city: Tullahoma
country: United States
facility: Shionogi Research Site
state: Tennessee
city: Channelview
country: United States
facility: Shionogi Research Site
state: Texas
city: Fort Worth
country: United States
facility: Shionogi Research Site
state: Texas
city: Groesbeck
country: United States
facility: Shionogi Research Site
state: Texas
city: Houston
country: United States
facility: Shionogi Research Site
state: Texas
city: Plano
country: United States
facility: Shionogi Research Site
state: Texas
city: San Antonio
country: United States
facility: Shionogi Research Site
state: Texas
city: Chesapeake
country: United States
facility: Shionogi Research Site
state: Virginia
city: Chester
country: United States
facility: Shionogi Research Site
state: Virginia
city: Tacoma
country: United States
facility: Shionogi Research Site
state: Washington
city: Clarksburg
country: United States
facility: Shionogi Research Site
state: West Virginia
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References:
citation: Hale ME, Wild JE, Yamada T, Yokota T, Tack J, Andresen V, Drewes AM. Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives. Therap Adv Gastroenterol. 2021 Jul 31;14:17562848211032320. doi: 10.1177/17562848211032320. eCollection 2021.
citation: Camilleri M, Hale M, Morlion B, Tack J, Webster L, Wild J. Naldemedine Improves Patient-Reported Outcomes of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain in the COMPOSE Phase 3 Studies. J Pain Res. 2021 Jul 16;14:2179-2189. doi: 10.2147/JPR.S282738. eCollection 2021.
citation: Tack J, Camilleri M, Hale M, Morlion B, Nalamachu S, Webster L, Wild J. Establishing Minimal Clinically Important Differences in Quality of Life Measures in Opioid-Induced Constipation. Clin Gastroenterol Hepatol. 2022 Apr;20(4):855-863. doi: 10.1016/j.cgh.2021.05.004. Epub 2021 Aug 5.
citation: Webster LR, Hale ME, Yamada T, Wild JE. A Renal Impairment Subgroup Analysis of the Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy. J Pain Res. 2020 Mar 24;13:605-612. doi: 10.2147/JPR.S237833. eCollection 2020.
citation: Wild J, Webster L, Yamada T, Hale M. Safety and Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Non-Cancer Pain Receiving Opioid Therapy: A Subgroup Analysis of Patients >/= 65 Years of Age. Drugs Aging. 2020 Apr;37(4):271-279. doi: 10.1007/s40266-020-00753-2.
citation: Wild J, Yamada T, Arjona Ferreira JC, Hale M. Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials. Pain. 2019 Oct;160(10):2358-2364. doi: 10.1097/j.pain.0000000000001629.
citation: Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC. Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol. 2017 Aug;2(8):555-564. doi: 10.1016/S2468-1253(17)30105-X. Epub 2017 May 30.