Clinical trial NCT01965652: Long Term Safety of Naldemedine
Official title: A Randomized Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study to Evaluate the Long-term Safety of Naldemedine for 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: 1246
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 long-term safety of naldemedine for the treatment of constipation due to opioid therapy.


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 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 may or may not be on a routine laxative regimen at the time of Screening

Exclusion Criteria

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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of study drug up to 14 days after the last dose of study drug (54 weeks).
Secondary outcomes:
measure: Change From Baseline in the Number of Bowel Movements Per Week
timeFrame: Baseline and Weeks 12, 24, 36, and 52
measure: Percentage of Participants Meeting Each Criterion of Laxative Use
timeFrame: From 28 days prior to screening until the end of the treatment period (total of 56 weeks)
measure: Change From Baseline in the Overall Score for Patient Assessment of Constipation Symptoms
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the PAC-SYM Abdominal-symptoms Domain Score
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the PAC-SYM Rectal-symptoms Domain Score
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the PAC-SYM Stool-symptoms Domain Score
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the Patient Assessment of Constipation Quality of Life Overall Score
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the Physical Discomfort Domain of PAC-QOL
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the Psychosocial Discomfort Domain of PAC-QOL
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the Worries and Concerns Domain of PAC-QOL
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Change From Baseline in the Satisfaction Domain of PAC-QOL
timeFrame: Baseline and Weeks 2, 12, 24, 36, and 52
measure: Participant Global Satisfaction
timeFrame: Week 52 or early termination visit
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Shionogi Research Site
state: Alabama
city: Mobile
country: United States
facility: Shionogi Research Site
state: Alabama
city: Chandler
country: United States
facility: Shionogi Research Site
state: Arizona
city: Glendale
country: United States
facility: Shionogi Research Site
state: Arizona
city: Goodyear
country: United States
facility: Shionogi Research Site
state: Arizona
city: Mesa
country: United States
facility: Shionogi Research Site
state: Arizona
city: Phoenix
country: United States
facility: Shionogi Research Site
state: Arizona
city: Tucson
country: United States
facility: Shionogi Research Site
state: Arizona
city: Fountain Valley
country: United States
facility: Shionogi Research Site
state: California
city: Garden Grove
country: United States
facility: Shionogi Research Site
state: California
city: Glendale
country: United States
facility: Shionogi Research Site
state: California
city: Long Beach
country: United States
facility: Shionogi Research Site
state: California
city: Los Angeles
country: United States
facility: Shionogi Research Site
state: California
city: Oceanside
country: United States
facility: Shionogi Research Site
state: California
city: Sacramento
country: United States
facility: Shionogi Research Site
state: California
city: Santa Ana
country: United States
facility: Shionogi Research Site
state: California
city: Upland
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facility: Shionogi Research Site
state: California
city: Colorado Springs
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facility: Shionogi Research Site
state: Colorado
city: Boynton Beach
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facility: Shionogi Research Site
state: Florida
city: Brandon
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facility: Shionogi Research Site
state: Florida
city: Brooksville
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facility: Shionogi Research Site
state: Florida
city: Clearwater
country: United States
facility: Shionogi Research Site
state: Florida
city: Fort Myers
country: United States
facility: Shionogi Research Site
state: Florida
city: Jacksonville
country: United States
facility: Shionogi Research Site
state: Florida
city: Lake City
country: United States
facility: Shionogi Research Site
state: Florida
city: Lakeland
country: United States
facility: Shionogi Research Site
state: Florida
city: Orlando
country: United States
facility: Shionogi Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Shionogi Research Site
state: Florida
city: South Miami
country: United States
facility: Shionogi Research Site
state: Florida
city: Tampa
country: United States
facility: Shionogi Research Site
state: Florida
city: Atlanta
country: United States
facility: Shionogi Research Site
state: Georgia
city: Blue Ridge
country: United States
facility: Shionogi Research Site
state: Georgia
city: Decatur
country: United States
facility: Shionogi Research Site
state: Georgia
city: Savannah
country: United States
facility: Shionogi Research Site
state: Georgia
city: Boise
country: United States
facility: Shionogi Research Site
state: Idaho
city: Aurora
country: United States
facility: Shionogi Research Site
state: Illinois
city: Bloomington
country: United States
facility: Shionogi Research Site
state: Illinois
city: Decatur
country: United States
facility: Shionogi Research Site
state: Illinois
city: Rockford
country: United States
facility: Shionogi Research Site
state: Illinois
city: Schaumburg
country: United States
facility: Shionogi Research Site
state: Illinois
city: Evansville
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facility: Shionogi Research Site
state: Indiana
city: Lafayette
country: United States
facility: Shionogi Research Site
state: Indiana
city: Valparaiso
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facility: Shionogi Research Site
state: Indiana
city: Augusta
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facility: Shionogi Research Site
state: Kansas
city: Newton
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facility: Shionogi Research Site
state: Kansas
city: Wichita
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facility: Shionogi Research Site
state: Kansas
city: Hartford
country: United States
facility: Shionogi Research Site
state: Kentucky
city: Eunice
country: United States
facility: Shionogi Research Site
state: Louisiana
city: Lake Charles
country: United States
facility: Shionogi Research Site
state: Louisiana
city: Mandeville
country: United States
facility: Shionogi Research Site
state: Louisiana
city: Brockton
country: United States
facility: Shionogi Research Site
state: Massachusetts
city: Fall River
country: United States
facility: Shionogi Research Site
state: Massachusetts
city: New Bedford
country: United States
facility: Shionogi Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Shionogi Research Site
state: Michigan
city: Saginaw
country: United States
facility: Shionogi Research Site
state: Michigan
city: Traverse City
country: United States
facility: Shionogi Research Site
state: Michigan
city: Biloxi
country: United States
facility: Shionogi Research Site
state: Mississippi
city: Fremont
country: United States
facility: Shionogi Research Site
state: Nebraska
city: Omaha
country: United States
facility: Shionogi Research Site
state: Nebraska
city: Henderson
country: United States
facility: Shionogi Research Site
state: Nevada
city: Las Vegas
country: United States
facility: Shionogi Research Site
state: Nevada
city: Trenton
country: United States
facility: Shionogi Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Shionogi Research Site
state: New Mexico
city: New York
country: United States
facility: Shionogi Research Site
state: New York
city: Greensboro
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Shionogi Research Site
state: North Carolina
city: Akron
country: United States
facility: Shionogi Research Site
state: Ohio
city: Canton
country: United States
facility: Shionogi Research Site
state: Ohio
city: Columbus
country: United States
facility: Shionogi Research Site
state: Ohio
city: Groveport
country: United States
facility: Shionogi Research Site
state: Ohio
city: Kettering
country: United States
facility: Shionogi Research Site
state: Ohio
city: Lebanon
country: United States
facility: Shionogi Research Site
state: Ohio
city: Marion
country: United States
facility: Shionogi Research Site
state: Ohio
city: Munroe Falls
country: United States
facility: Shionogi Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Shionogi Research Site
state: Oklahoma
city: Tulsa
country: United States
facility: Shionogi Research Site
state: Oklahoma
city: Portland
country: United States
facility: Shionogi Research Site
state: Oregon
city: Huntingdon Valley
country: United States
facility: Shionogi Research Site
state: Pennsylvania
city: Jenkintown
country: United States
facility: Shionogi Research Site
state: Pennsylvania
city: Lansdale
country: United States
facility: Shionogi Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Shionogi Research Site
state: South Carolina
city: Greer
country: United States
facility: Shionogi Research Site
state: South Carolina
city: Myrtle Beach
country: United States
facility: Shionogi Research Site
state: South Carolina
city: Summerville
country: United States
facility: Shionogi Research Site
state: South Carolina
city: Bristol
country: United States
facility: Shionogi Research Site
state: Tennessee
city: Milan
country: United States
facility: Shionogi Research Site
state: Tennessee
city: Nashville
country: United States
facility: Shionogi Research Site
state: Tennessee
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: Hurst
country: United States
facility: Shionogi Research Site
state: Texas
city: Sugar Land
country: United States
facility: Shionogi Research Site
state: Texas
city: Bountiful
country: United States
facility: Shionogi Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Shionogi Research Site
state: Utah
city: South Ogden
country: United States
facility: Shionogi Research Site
state: Utah
city: Richmond
country: United States
facility: Shionogi Research Site
state: Virginia
city: Bellevue
country: United States
facility: Shionogi Research Site
state: Washington
city: Edmonds
country: United States
facility: Shionogi Research Site
state: Washington
city: Adelaide
country: Australia
facility: Shionogi Research Site
city: Bedford Park
country: Australia
facility: Shionogi Research Site
city: Camperdown
country: Australia
facility: Shionogi Research Site
city: Carina Heights
country: Australia
facility: Shionogi Research Site
city: Caulfield South
country: Australia
facility: Shionogi Research Site
city: Malvern East
country: Australia
facility: Shionogi Research Site
city: Nambour
country: Australia
facility: Shionogi Research Site
city: Sherwood
country: Australia
facility: Shionogi Research Site
city: St Leonards
country: Australia
facility: Shionogi Research Site
city: Linz
country: Austria
facility: Shionogi Research Site
city: Vienna
country: Austria
facility: Shionogi Research Site
city: Zams
country: Austria
facility: Shionogi Research Site
city: London
country: Canada
facility: Shionogi Research Site
city: Mirabel
country: Canada
facility: Shionogi Research Site
city: Sarnia
country: Canada
facility: Shionogi Research Site
city: Sherbrooke
country: Canada
facility: Shionogi Research Site
city: Toronto
country: Canada
facility: Shionogi Research Site
city: Vancouver
country: Canada
facility: Shionogi Research Site
city: Benesov
country: Czechia
facility: Shionogi Research Site
city: Olomouc
country: Czechia
facility: Shionogi Research Site
city: Ostrava
country: Czechia
facility: Shionogi Research Site
city: Pardubice
country: Czechia
facility: Shionogi Research Site
city: Pribram V- Zdabor
country: Czechia
facility: Shionogi Research Site
city: Glostrup
country: Denmark
facility: Shionogi Research Site
city: Hellerup
country: Denmark
facility: Shionogi Research Site
city: Odense
country: Denmark
facility: Shionogi Research Site
city: Soulaine Sur Aubance
country: France
facility: Shionogi Research Site
city: Berlin
country: Germany
facility: Shionogi Research Site
city: Dresden
country: Germany
facility: Shionogi Research Site
city: Halle
country: Germany
facility: Shionogi Research Site
city: Hamburg
country: Germany
facility: Shionogi Research Site
city: Hannover
country: Germany
facility: Shionogi Research Site
city: Kassel
country: Germany
facility: Shionogi Research Site
city: Leipzig
country: Germany
facility: Shionogi Research Site
city: Luenen
country: Germany
facility: Shionogi Research Site
city: Mainz
country: Germany
facility: Shionogi Research Site
city: Muenster
country: Germany
facility: Shionogi Research Site
city: Stadtroda
country: Germany
facility: Shionogi Research Site
city: Balatonfuered
country: Hungary
facility: Shionogi Research Site
city: Budapest
country: Hungary
facility: Shionogi Research Site
city: Debrecen
country: Hungary
facility: Shionogi Research Site
city: Hatvan
country: Hungary
facility: Shionogi Research Site
city: Szikszo
country: Hungary
facility: Shionogi Research Site
city: Beer Sheva
country: Israel
facility: Shionogi Research Site
city: Haifa
country: Israel
facility: Shionogi Research Site
city: Tel Aviv
country: Israel
facility: Shionogi Research Site
city: Tel Hashomer
country: Israel
facility: Shionogi Research Site
city: Asti
country: Italy
facility: Shionogi Research Site
city: Catania
country: Italy
facility: Shionogi Research Site
city: Chieti
country: Italy
facility: Shionogi Research Site
city: Firenze
country: Italy
facility: Shionogi Research Site
city: Napoli
country: Italy
facility: Shionogi Research Site
city: Rionero in Vulture
country: Italy
facility: Shionogi Research Site
city: Roma
country: Italy
facility: Shionogi Research Site
city: Rome
country: Italy
facility: Shionogi Research Site
city: Chorzów
country: Poland
facility: Shionogi Research Site
city: Gdańsk
country: Poland
facility: Shionogi Research Site
city: Katowice
country: Poland
facility: Shionogi Research Site
city: Lublin
country: Poland
facility: Shionogi Research Site
city: Alberton
country: South Africa
facility: Shionogi Research Site
city: Lyttelton Centurion
country: South Africa
facility: Shionogi Research Site
city: Muckleneuk Pretoria
country: South Africa
facility: Shionogi Research Site
city: Pretoria West Pretoria
country: South Africa
facility: Shionogi Research Site
city: Worcester
country: South Africa
facility: Shionogi Research Site
city: Barcelona
country: Spain
facility: Shionogi Research Site
city: Girona
country: Spain
facility: Shionogi Research Site
city: Sevilla
country: Spain
facility: Shionogi Research Site
city: Skene
country: Sweden
facility: Shionogi Research Site
city: Stockholm
country: Sweden
facility: Shionogi Research Site
city: Bath
country: United Kingdom
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: Chesterfield
country: United Kingdom
facility: Shionogi Research Site
city: Chestfield Kent
country: United Kingdom
facility: Shionogi Research Site
city: Daventry Northants
country: United Kingdom
facility: Shionogi Research Site
city: Devon
country: United Kingdom
facility: Shionogi Research Site
city: Epworth Doncaster
country: United Kingdom
facility: Shionogi Research Site
city: Harrogate
country: United Kingdom
facility: Shionogi Research Site
city: Hinckley
country: United Kingdom
facility: Shionogi Research Site
city: Liverpool
country: United Kingdom
facility: Shionogi Research Site
city: Norwich
country: United Kingdom
facility: Shionogi Research Site
city: Oldham
country: United Kingdom
facility: Shionogi Research Site
city: Peterborough
country: United Kingdom
facility: Shionogi Research Site
city: Randalstown, County Antrim
country: United Kingdom
facility: Shionogi Research Site
city: Spiro Close, Pulborough West Sussex
country: United Kingdom
facility: Shionogi Research Site
city: Wellingborough Northamptonshire
country: United Kingdom
facility: Shionogi Research Site
city: York
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: 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: 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.