Efficacy and Safety of Naldemedine in the Treatment of Opioid-induced Constipation

NCT01965158 | Completed Phase 3 Results DMC

• 2 other identifiers: 1314V92312013-002241-11
• Study Type: interventional
• Target: 547
• Locations: 7 countries
• Sites: 65

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.

Conditions

Opioid-induced Constipation

Keywords

Opioid-induced Constipation

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response

  A bowel movement and constipation assessment (BMCA) was completed by participants every day during the screening and treatment periods to record information about bowel movements (BMs) and constipation. An SBM was defined as a bowel movement that occurred without the use of rescue laxative therapy during the 24 hours prior to the BM. A responder was defined as a participant having 9 or more positive response weeks out of the 12-week Treatment Period and 3 positive response weeks out of last 4 weeks of the 12-week Treatment Period. A positive response week was defined as ≥ 3 SBMs per week and an increase from baseline of ≥ 1 SBM per week for that week. If a participant had less than 4 days of diary entries for a week, that week was treated as a "non-response" week. Any participant with insufficient primary endpoint data (data for less than 9 out of 12 weeks of the Treatment Period or less than 3 out of the last 4 weeks of the 12-week Treatment Period) was treated as a non-responder.

  12-week treatment period

Secondary Outcomes (4)

• Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week

  Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)

• Change From Baseline to Week 1 in the Number of Spontaneous Bowel Movements Per Week

  Baseline and Week 1

• Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Complete Spontaneous Bowel Movements Per Week

  Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)

• Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements With No Straining Per Week

  Baseline and the last 2 weeks of the treatment period (Weeks 11 and 12 for participants who completed 12 weeks of treatment)

Study Arms (2)

Naldemedine

EXPERIMENTAL

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

Drug: Naldemedine

Placebo

PLACEBO COMPARATOR

Participants received matching placebo orally once daily for 12 weeks.

Drug: Placebo

Interventions

Naldemedine DRUG

Naldemedine 0.2 mg tablet taken orally once a day

Also known as: S 297995, Symproic®

Naldemedine

Placebo DRUG

Placebo tablet taken orally once a day

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shionogi: lead

Study Sites (65)

Shionogi Research Site

Birmingham, Alabama, United States

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Shionogi Research Site

Phoenix, Arizona, United States

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Shionogi Research Site

Fresno, California, United States

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Shionogi Research Site

Long Beach, California, United States

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Shionogi Research Site

National City, California, United States

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Shionogi Research Site

North Hollywood, California, United States

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Shionogi Research Site

Oceanside, California, United States

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Shionogi Research Site

Golden, Colorado, United States

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Shionogi Research Site

Miami, Florida, United States

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Shionogi Research Site

Miami Springs, Florida, United States

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Shionogi Research Site

Orlando, Florida, United States

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Shionogi Research Site

Sarasota, Florida, United States

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Shionogi Research Site

West Palm Beach, Florida, United States

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Shionogi Research Site

Winter Park, Florida, United States

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Shionogi Research Site

Marietta, Georgia, United States

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Shionogi Research Site

Shreveport, Louisiana, United States

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Shionogi Research Site

Caro, Michigan, United States

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Shionogi Research Site

Flint, Michigan, United States

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Shionogi Research Site

Hazelwood, Missouri, United States

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Shionogi Research Site

Las Vegas, Nevada, United States

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Shionogi Research Site

Belvidere, New Jersey, United States

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Shionogi Research Site

East Brunswick, New Jersey, United States

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Shionogi Research Site

Albuquerque, New Mexico, United States

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Shionogi Research Site

Great Neck, New York, United States

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Shionogi Research Site

Hollis, New York, United States

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Shionogi Research Site

New Windsor, New York, United States

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Shionogi Research Site

Winston-Salem, North Carolina, United States

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Shionogi Research Site

Cincinnati, Ohio, United States

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Shionogi Research Site

Oklahoma City, Oklahoma, United States

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Shionogi Research Site

Medford, Oregon, United States

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Shionogi Research Site

West Reading, Pennsylvania, United States

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Shionogi Research Site

Chattanooga, Tennessee, United States

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Shionogi Research Site

Arlington, Texas, United States

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Shionogi Research Site

Austin, Texas, United States

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Shionogi Research Site

Dallas, Texas, United States

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Shionogi Research Site

Houston, Texas, United States

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Shionogi Research Site

San Antonio, Texas, United States

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Shionogi Research Site

Sankt Pölten, Austria

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Shionogi Research Site

Vienna, Austria

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Shionogi Research Site

Hradec Králové, Czechia

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Shionogi Research Site

Liberec, Czechia

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Shionogi Research Site

Pardubice, Czechia

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Shionogi Research Site

Prague, Czechia

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Shionogi Research Site

Vysoké Mýto, Czechia

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Shionogi Research Site

Berlin, Germany

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Shionogi Research Site

Eichstätt, Germany

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Shionogi Research Site

Frankfurt am Main, Germany

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Shionogi Research Site

Bialystok, Poland

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Shionogi Research Site

Bydgoszcz, Poland

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Shionogi Research Site

Czeladź, Poland

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Shionogi Research Site

Gorzów Wielkopolski, Poland

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Shionogi Research Site

Warsaw, Poland

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Shionogi Research Site

Alicante, Spain

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Shionogi Research Site

Cadiz, Spain

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Shionogi Research Site

Madrid, Spain

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Shionogi Research Site

Belfast, United Kingdom

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Shionogi Research Site

Bexhill-on-Sea East Sussex, United Kingdom

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Shionogi Research Site

Crownhill Plymouth, United Kingdom

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Shionogi Research Site

Fowey Cornwall, United Kingdom

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Shionogi Research Site

Liskeard Cornwall, United Kingdom

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Shionogi Research Site

London, United Kingdom

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Shionogi Research Site

Penzance Cornwall, United Kingdom

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Shionogi Research Site

Saint Austell Cornwall, United Kingdom

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Shionogi Research Site

Soham Ely Cambs, United Kingdom

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Shionogi Research Site

Tomairt, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 34377150 DERIVED

• 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.

  PMID: 34295186 DERIVED

• 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.

  PMID: 33965574 DERIVED

• 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.

  PMID: 32280263 DERIVED

• 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.

  PMID: 32086791 DERIVED

• 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.

  PMID: 31145214 DERIVED

• 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.

  PMID: 28576452 DERIVED

MeSH Terms

Conditions

Opioid-Induced Constipation

Interventions

naldemedine

Condition Hierarchy (Ancestors)

Constipation; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Shionogi Clinical Trials Administrator
• Organization: Shionogi Inc.

shionogiclintrials-admin@shionogi.co.jp

800-849-9707

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2013
• First Posted: October 18, 2013
• Study Start: August 29, 2013
• Primary Completion: January 22, 2015
• Study Completion: January 22, 2015
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2016-04

Locations

DE (3); CZ (5); PL (5); ES (3); GB (10); US (37); AU (2)