Efficacy and Safety of Naldemedine in Treating Opioid-induced Constipation

NCT ID: NCT01993940

Last Updated: 2017-05-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

553 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-04

Study Completion Date

2015-06-09

Brief Summary

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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.

Detailed Description

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Conditions

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Opioid-induced Constipation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Naldemedine

Participants received 0.2 mg naldemedine orally once daily for 12 weeks.

Group Type EXPERIMENTAL

Naldemedine

Intervention Type DRUG

Naldemedine 0.2 mg tablet taken orally once a day

Placebo

Participants received matching placebo orally once daily for 12 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo tablet taken orally once a day

Interventions

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Naldemedine

Naldemedine 0.2 mg tablet taken orally once a day

Intervention Type DRUG

Placebo

Placebo tablet taken orally once a day

Intervention Type DRUG

Other Intervention Names

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S-297995 Symproic®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shionogi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shionogi Clinical Trials Administrator Clinical Support Help Line

Role: STUDY_DIRECTOR

Shionogi

Locations

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Shionogi Research Site

Birmingham, Alabama, United States

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Homewood, Alabama, United States

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Goodyear, Arizona, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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Buena Park, California, United States

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Corona, California, United States

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Gold River, California, United States

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Los Angeles, California, United States

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Modesto, California, United States

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Pasadena, California, United States

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Coral Gables, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Miami Beach, Florida, United States

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Plantation, Florida, United States

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Columbus, Georgia, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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West Des Moines, Iowa, United States

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Edgewood, Kentucky, United States

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Crowley, Louisiana, United States

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Kalamazoo, Michigan, United States

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Traverse City, Michigan, United States

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Butte, Montana, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Omaha, Nevada, United States

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Albuquerque, New Mexico, United States

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Hopewell Junction, New York, United States

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Mooresville, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Dayton, Ohio, United States

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Marion, Ohio, United States

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Media, Pennsylvania, United States

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Spartanburg, South Carolina, United States

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Knoxville, Tennessee, United States

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Tullahoma, Tennessee, United States

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Channelview, Texas, United States

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Fort Worth, Texas, United States

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Groesbeck, Texas, United States

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Houston, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Chesapeake, Virginia, United States

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Chester, Virginia, United States

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Tacoma, Washington, United States

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Shionogi Research Site

Clarksburg, West Virginia, United States

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Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34377150 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34295186 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33965574 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32280263 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32086791 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31145214 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28576452 (View on PubMed)

Other Identifiers

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2013-002948-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1315V9232

Identifier Type: -

Identifier Source: org_study_id

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