Long Term Safety of Naldemedine

NCT01965652 | Completed Phase 3 Results DMC

• 1 other identifier: 1326V9235
• Study Type: interventional
• Target: 1,246
• Locations: 15 countries
• Sites: 177

Brief Summary

The purpose of this study is to evaluate the long-term safety of naldemedine for the treatment of constipation due to opioid therapy.

Conditions

Opioid-induced Constipation

Keywords

Opioid Induced Constipation

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  A serious adverse event was defined as any adverse event (AE) that resulted in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life threatening, or require hospitalization were considered an SAE when, based upon appropriate medical judgment, they jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. Adverse drug reactions (ADRs) were defined as adverse events that were considered by the investigator to be definitely, probably, or possibly related to study drug. Serious ADRs were defined as serious AEs considered by the investigator to be definitely, probably, or possibly related to study drug.

  From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).

Secondary Outcomes (12)

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

  Baseline and Weeks 12, 24, 36, and 52

• Percentage of Participants Meeting Each Criterion of Laxative Use

  From 28 days prior to screening until the end of the treatment period (total of 56 weeks)

• Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms

  Baseline and Weeks 2, 12, 24, 36, and 52

• Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score

  Baseline and Weeks 2, 12, 24, 36, and 52

• Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score

  Baseline and Weeks 2, 12, 24, 36, and 52

Study Arms (2)

Naldemedine

EXPERIMENTAL

Participants received 0.2 mg naldemedine tablets orally once daily for 52 weeks.

Drug: Naldemedine

Placebo

PLACEBO COMPARATOR

Participants received matching placebo tablets orally once daily for 52 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 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 may or may not be on a routine laxative regimen at the time of Screening

You may not qualify if:

• Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
• Evidence of active medical diseases affecting bowel transit
• History 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
• Current use of any prohibited medication including opioid antagonists, partial or mixed agonists/antagonists

Sponsors & Collaborators

• Shionogi: lead

Study Sites (186)

Shionogi Research Site

Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Chandler, Arizona, United States

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Glendale, Arizona, United States

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Goodyear, Arizona, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Fountain Valley, California, United States

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Garden Grove, California, United States

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Glendale, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Oceanside, California, United States

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Sacramento, California, United States

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Santa Ana, California, United States

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Upland, California, United States

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Colorado Springs, Colorado, United States

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Boynton Beach, Florida, United States

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Brandon, Florida, United States

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Brooksville, Florida, United States

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Clearwater, Florida, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Lake City, Florida, United States

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Lakeland, Florida, United States

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Orlando, Florida, United States

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South Miami, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Blue Ridge, Georgia, United States

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Decatur, Georgia, United States

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Savannah, Georgia, United States

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Boise, Idaho, United States

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Aurora, Illinois, United States

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Bloomington, Illinois, United States

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Decatur, Illinois, United States

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Rockford, Illinois, United States

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Schaumburg, Illinois, United States

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Evansville, Indiana, United States

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Lafayette, Indiana, United States

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Valparaiso, Indiana, United States

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Augusta, Kansas, United States

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Newton, Kansas, United States

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Wichita, Kansas, United States

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Hartford, Kentucky, United States

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Eunice, Louisiana, United States

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Lake Charles, Louisiana, United States

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Mandeville, Louisiana, United States

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Brockton, Massachusetts, United States

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Fall River, Massachusetts, United States

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New Bedford, Massachusetts, United States

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Rochester, Michigan, United States

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Saginaw, Michigan, United States

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Traverse City, Michigan, United States

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Biloxi, Mississippi, United States

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Fremont, Nebraska, United States

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Omaha, Nebraska, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Trenton, New Jersey, United States

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Albuquerque, New Mexico, United States

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New York, New York, United States

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Greensboro, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Akron, Ohio, United States

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Canton, Ohio, United States

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Columbus, Ohio, United States

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Groveport, Ohio, United States

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Kettering, Ohio, United States

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Lebanon, Ohio, United States

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Marion, Ohio, United States

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Munroe Falls, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Huntingdon Valley, Pennsylvania, United States

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Jenkintown, Pennsylvania, United States

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Lansdale, Pennsylvania, United States

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Charleston, South Carolina, United States

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Greer, South Carolina, United States

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Myrtle Beach, South Carolina, United States

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Summerville, South Carolina, United States

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Bristol, Tennessee, United States

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Milan, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Hurst, Texas, United States

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Sugar Land, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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South Ogden, Utah, United States

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Richmond, Virginia, United States

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Bellevue, Washington, United States

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Edmonds, Washington, United States

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Adelaide, Australia

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Bedford Park, Australia

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Camperdown, Australia

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Carina Heights, Australia

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Caulfield South, Australia

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Malvern East, Australia

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Nambour, Australia

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Sherwood, Australia

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St Leonards, Australia

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Linz, Austria

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Vienna, Austria

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Zams, Austria

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London, Canada

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Mirabel, Canada

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Sarnia, Canada

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Sherbrooke, Canada

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Toronto, Canada

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Vancouver, Canada

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Benešov, Czechia

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Olomouc, Czechia

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Ostrava, Czechia

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Pardubice, Czechia

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Pribram V- Zdabor, Czechia

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Glostrup Municipality, Denmark

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Hellerup, Denmark

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Odense, Denmark

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Soulaine Sur Aubance, France

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Berlin, Germany

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Dresden, Germany

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Halle, Germany

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Hamburg, Germany

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Hanover, Germany

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Kassel, Germany

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Leipzig, Germany

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Lünen, Germany

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Mainz, Germany

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Münster, Germany

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Stadtroda, Germany

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Balatonfüred, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Hatvan, Hungary

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Szikszó, Hungary

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Beersheba, Israel

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Haifa, Israel

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Tel Aviv, Israel

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Tel Litwinsky, Israel

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Asti, Italy

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Catania, Italy

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Chieti, Italy

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Florence, Italy

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Napoli, Italy

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Rionero in Vulture, Italy

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Roma, Italy

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Rome, Italy

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Chorzów, Poland

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Gdansk, Poland

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Katowice, Poland

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Lublin, Poland

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Alberton, South Africa

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Lyttelton Centurion, South Africa

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Muckleneuk Pretoria, South Africa

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Pretoria West Pretoria, South Africa

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Worcester, South Africa

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Barcelona, Spain

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Girona, Spain

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Seville, Spain

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Skene, Sweden

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Stockholm, Sweden

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Bath, United Kingdom

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Belfast, United Kingdom

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Bexhill on Sea East Sussex, United Kingdom

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Chesterfield, United Kingdom

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Chestfield Kent, United Kingdom

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Daventry Northants, United Kingdom

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Devon, United Kingdom

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Epworth Doncaster, United Kingdom

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Harrogate, United Kingdom

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Hinckley, United Kingdom

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Liverpool, United Kingdom

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Norwich, United Kingdom

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Oldham, United Kingdom

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Peterborough, United Kingdom

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Randalstown, County Antrim, United Kingdom

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Spiro Close, Pulborough West Sussex, United Kingdom

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Wellingborough Northamptonshire, United Kingdom

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York, United Kingdom

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Related Publications (3)

• 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

• 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

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: October 15, 2013
• First Posted: October 18, 2013
• Study Start: September 24, 2013
• Primary Completion: January 12, 2016
• Study Completion: January 12, 2016
• Last Updated: April 18, 2018
• Results First Posted: May 30, 2017

Record last verified: 2018-04

Locations

IL (4); ZA (5); PL (4); HU (5); IT (8); ES (3); CA (6); DK (3); SE (2); US (99); AU (3); DE (11); FR (1); CZ (5); GB (18)