Clinical trial NCT01965158: Efficacy and Safety of Naldemedine in the Treatment of 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: 2013-10-18
Enrollment: 547
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:

1. Subjects aged 18 to 80 years inclusive at the time of informed consent
2. Subjects must have non-malignant chronic pain treated with opioids and must have opioid-induced constipation (OIC)
3. Subjects must be treated with a stable opioid regimen at a total daily dose on average of ≥ 30 mg equivalents of oral morphine sulfate
4. 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
5. Subjects must meet opioid-induced constipation criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary

Exclusion Criteria:

1. Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
2. Evidence of active medical diseases affecting bowel transit
3. History or presence of pelvic disorders that may be a cause of constipation
4. Surgery (except for minor procedures) within 60 days of Screening
5. 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)
6. Subjects who have never taken laxatives for the treatment of OIC
7. 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
8. 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: Phoenix
country: United States
facility: Shionogi Research Site
state: Arizona
city: Fresno
country: United States
facility: Shionogi Research Site
state: California
city: Long Beach
country: United States
facility: Shionogi Research Site
state: California
city: National City
country: United States
facility: Shionogi Research Site
state: California
city: North Hollywood
country: United States
facility: Shionogi Research Site
state: California
city: Oceanside
country: United States
facility: Shionogi Research Site
state: California
city: Golden
country: United States
facility: Shionogi Research Site
state: Colorado
city: Miami Springs
country: United States
facility: Shionogi Research Site
state: Florida
city: Miami
country: United States
facility: Shionogi Research Site
state: Florida
city: Orlando
country: United States
facility: Shionogi Research Site
state: Florida
city: Sarasota
country: United States
facility: Shionogi Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Shionogi Research Site
state: Florida
city: Winter Park
country: United States
facility: Shionogi Research Site
state: Florida
city: Marietta
country: United States
facility: Shionogi Research Site
state: Georgia
city: Shreveport
country: United States
facility: Shionogi Research Site
state: Louisiana
city: Caro
country: United States
facility: Shionogi Research Site
state: Michigan
city: Flint
country: United States
facility: Shionogi Research Site
state: Michigan
city: Hazelwood
country: United States
facility: Shionogi Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Shionogi Research Site
state: Nevada
city: Belvidere
country: United States
facility: Shionogi Research Site
state: New Jersey
city: East Brunswick
country: United States
facility: Shionogi Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Shionogi Research Site
state: New Mexico
city: Great Neck
country: United States
facility: Shionogi Research Site
state: New York
city: Hollis
country: United States
facility: Shionogi Research Site
state: New York
city: New Windsor
country: United States
facility: Shionogi Research Site
state: New York
city: Winston-Salem
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Shionogi Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Shionogi Research Site
state: Oklahoma
city: Medford
country: United States
facility: Shionogi Research Site
state: Oregon
city: West Reading
country: United States
facility: Shionogi Research Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Shionogi Research Site
state: Tennessee
city: Arlington
country: United States
facility: Shionogi Research Site
state: Texas
city: Austin
country: United States
facility: Shionogi Research Site
state: Texas
city: Dallas
country: United States
facility: Shionogi Research Site
state: Texas
city: Houston
country: United States
facility: Shionogi Research Site
state: Texas
city: San Antonio
country: United States
facility: Shionogi Research Site
state: Texas
city: St. Poelten
country: Austria
facility: Shionogi Research Site
city: Vienna
country: Austria
facility: Shionogi Research Site
city: Hradec Kralove
country: Czechia
facility: Shionogi Research Site
city: Liberec
country: Czechia
facility: Shionogi Research Site
city: Pardubice
country: Czechia
facility: Shionogi Research Site
city: Prague
country: Czechia
facility: Shionogi Research Site
city: Vysoke Myto
country: Czechia
facility: Shionogi Research Site
city: Berlin
country: Germany
facility: Shionogi Research Site
city: Eichstaett
country: Germany
facility: Shionogi Research Site
city: Frankfurt am Main
country: Germany
facility: Shionogi Research Site
city: Bialystok
country: Poland
facility: Shionogi Research Site
city: Bydgoszcz
country: Poland
facility: Shionogi Research Site
city: Czeladź
country: Poland
facility: Shionogi Research Site
city: Gorzów Wielkopolski
country: Poland
facility: Shionogi Research Site
city: Warszawa
country: Poland
facility: Shionogi Research Site
city: Alicante
country: Spain
facility: Shionogi Research Site
city: Cádiz
country: Spain
facility: Shionogi Research Site
city: Madrid
country: Spain
facility: Shionogi Research Site
city: Belfast
country: United Kingdom
facility: Shionogi Research Site
city: Bexhill-on-Sea East Sussex
country: United Kingdom
facility: Shionogi Research Site
city: Crownhill Plymouth
country: United Kingdom
facility: Shionogi Research Site
city: Fowey Cornwall
country: United Kingdom
facility: Shionogi Research Site
city: Liskeard Cornwall
country: United Kingdom
facility: Shionogi Research Site
city: London
country: United Kingdom
facility: Shionogi Research Site
city: Penzance Cornwall
country: United Kingdom
facility: Shionogi Research Site
city: Soham Ely Cambs
country: United Kingdom
facility: Shionogi Research Site
city: St Austell Cornwall
country: United Kingdom
facility: Shionogi Research Site
city: Tomairt
country: United Kingdom
facility: Shionogi Research Site
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.