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Opioid-induced ConstipationPhase 3NCT01993940

Efficacy and Safety of Naldemedine in Treating Opioid-induced Constipation

A Phase 3 study testing Naldemedine in people with Opioid-induced Constipation, run by Shionogi at 49 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Opioid-induced Constipation
What is being tested?
Naldemedine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
553 participants
Where
49 sitesUnited States
Study dates
4 Nov 2013to 9 Jun 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

49 sites in 1 country.

49 sites in 1 country

United States49 sites
  • Shionogi Research Site

    Albuquerque, New Mexico

  • Shionogi Research Site

    Anaheim, California

  • Shionogi Research Site

    Birmingham, Alabama

  • Shionogi Research Site

    Buena Park, California

  • Shionogi Research Site

    Butte, Montana

  • Shionogi Research Site

    Channelview, Texas

  • Shionogi Research Site

    Chesapeake, Virginia

  • Shionogi Research Site

    Chester, Virginia

  • Shionogi Research Site

    Clarksburg, West Virginia

  • Shionogi Research Site

    Columbus, Georgia

  • Shionogi Research Site

    Coral Gables, Florida

  • Shionogi Research Site

    Corona, California

  • Shionogi Research Site

    Crowley, Louisiana

  • Shionogi Research Site

    Dayton, Ohio

  • Shionogi Research Site

    Edgewood, Kentucky

  • Shionogi Research Site

    Evansville, Indiana

  • Shionogi Research Site

    Fort Worth, Texas

  • Shionogi Research Site

    Gold River, California

  • Shionogi Research Site

    Goodyear, Arizona

  • Shionogi Research Site

    Groesbeck, Texas

  • Shionogi Research Site

    Hialeah, Florida

  • Shionogi Research Site

    Homewood, Alabama

  • Shionogi Research Site

    Hopewell Junction, New York

  • Shionogi Research Site

    Houston, Texas

  • Shionogi Research Site

    Indianapolis, Indiana

  • Shionogi Research Site

    Jacksonville, Florida

  • Shionogi Research Site

    Kalamazoo, Michigan

  • Shionogi Research Site

    Knoxville, Tennessee

  • Shionogi Research Site

    Las Vegas, Nevada

  • Shionogi Research Site

    Little Rock, Arkansas

  • Shionogi Research Site

    Los Angeles, California

  • Shionogi Research Site

    Marion, Ohio

  • Shionogi Research Site

    Media, Pennsylvania

  • Shionogi Research Site

    Miami, Florida

  • Shionogi Research Site

    Miami Beach, Florida

  • Shionogi Research Site

    Modesto, California

  • Shionogi Research Site

    Mooresville, North Carolina

  • Shionogi Research Site

    Omaha, Nebraska

  • Shionogi Research Site

    Omaha, Nevada

  • Shionogi Research Site

    Pasadena, California

  • Shionogi Research Site

    Plano, Texas

  • Shionogi Research Site

    Plantation, Florida

  • Shionogi Research Site

    San Antonio, Texas

  • Shionogi Research Site

    Spartanburg, South Carolina

  • Shionogi Research Site

    Tacoma, Washington

  • Shionogi Research Site

    Traverse City, Michigan

  • Shionogi Research Site

    Tullahoma, Tennessee

  • Shionogi Research Site

    West Des Moines, Iowa

  • Shionogi Research Site

    Winston-Salem, North Carolina

Other trials in United States

About this study

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

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.

Being tested
Naldemedine, Placebo
Keywords
Opioid-induced Constipation
Medical subject headings
Opioid-Induced Constipation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NaldemedineDrug

    Also called S-297995, Symproic®

    Naldemedine 0.2 mg tablet taken orally once a day

  • PlaceboDrug

    Placebo tablet taken orally once a day

Study groups in NCT01993940
Study groupRoleWhat they receive
NaldemedineExperimentalParticipants received 0.2 mg naldemedine orally once daily for 12 weeks.
Receives: Drug: Naldemedine
PlaceboPlacebo comparatorParticipants received matching placebo orally once daily for 12 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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 the 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

    Measured: 12-week treatment period

Secondary outcomes (4)
  1. Change From Baseline to the Last 2 Weeks of the Treatment Period in the Number of Spontaneous Bowel Movements Per Week

    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 a rescue laxative therapy during the 24 hours prior to the BM. Baseline was defined as the 14 days in the screening period prior to study drug administration.

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

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

    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 a rescue laxative therapy during the 24 hours prior to the BM. Baseline was defined as the 14 days in the screening period prior to study drug administration.

    Measured: Baseline and Week 1

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

    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. A complete spontaneous bowel movement (CSBM) was defined as an SBM which was accompanied by the feeling of complete evacuation.

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

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

    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. The severity of straining with each bowel movement was assessed on the following scale: 0=no straining, 1=mild straining, 2=moderate straining, 3=severe straining, 4=very severe straining. SBMs without straining were defined as SBMs with a straining score of 0.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2013 (estimated)
  2. Study start4 Nov 2013
  3. Primary completion9 Jun 2015
  4. Study completion9 Jun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
553 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01993940
Sponsor's protocol ID
1315V9232
Other IDs
2013-002948-91
Status last verified
May 2016
First submitted
19 Nov 2013
Last updated
30 May 2017
Data monitoring committee
Yes

Publications

  • 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. Ther Adv Gastroenterol. 2021 Jul 31;14:17562848211032320. doi: 10.1177/17562848211032320. eCollection 2021.

    PubMed 34377150
  • 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.

    PubMed 34295186
  • 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.

    PubMed 33965574
  • 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.

    PubMed 32280263
  • 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.

    PubMed 32086791
  • 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.

    PubMed 31145214
  • 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.

    PubMed 28576452

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Naldemedine in people with Opioid-induced Constipation, run by Shionogi at 49 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With a Spontaneous Bowel Movement (SBM) Response (time frame: 12-week treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01993940, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.

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