Clinical trial NCT01323790: Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Patients With Non-Cancer-Related Pain and Opioid-Induced Constipation (OIC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid-Induced Constipation (OIC)
Keywords: Non-Cancer-Related Pain
Opioid-Induced Constipation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-03-28
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
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 effect and safety of NKTR-118 treatment of opioid-induced constipation in patients with non-cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR).


Eligibility criteria: Inclusion Criteria:

* Provision of written informed consent prior to any study-specific procedures.
* Self-reported active symptoms of OIC at screening (\<3 SBMs/week and experiencing ≥1 reported symptom of hard/lumpy stools, straining, or sensation of incomplete evacuation/anorectal obstruction in at least 25% of BMs over the previous 4 weeks); and Documented confirmed OIC (\<3 SBMs/week on average over the 2-week OIC confirmation period.
* Receiving a stable maintenance opioid regimen consisting of a total daily dose of 30 mg to 1000 mg of oral morphine, or equianalgesic amount(s) of 1 or more other opioid therapies for a minimum of 4 weeks prior to screening for non-cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.
* Willingness to stop all laxatives and other bowel regimens including prune juice and herbal products throughout the 2-week OIC confirmation period and the 12-week treatment period, and to use only bisacodyl as rescue medication if a BM has not occurred within at least 72 hours of the last recorded BM.

Exclusion Criteria:

* Patients receiving Opioid regimen for treatment of pain related to cancer.
* History of cancer within 5 years from first study visit with the exception of basal cell cancer and squamous cell skin cancer.
* Medical conditions and treatments associated with diarrhea, intermittent loose stools, or constipation.
* Other issues to the gastrointestinal tract that could impose a risk to the patient.
* Pregnancy or lactation.

Primary outcomes:
measure: Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
Secondary outcomes:
measure: Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
timeFrame: 12 weeks
measure: Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
timeFrame: 12 weeks
measure: Change From Baseline in Degree of Straining
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Change From Baseline in Stool Consistency (Bristol Stool Scale)
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Change From Baseline in Mean Spontaneous Bowel Movements/Week
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
measure: Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
timeFrame: Baseline (Week 1) to end of treatment (Week 12)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Pell City
country: United States
facility: Research Site
state: Alabama
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
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state: Arizona
city: Sun Lakes
country: United States
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state: Arizona
city: Tucson
country: United States
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state: Arizona
city: Jonesboro
country: United States
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state: Arkansas
city: Little Rock
country: United States
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state: Arkansas
city: North Little Rock
country: United States
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state: Arkansas
city: Sherwood
country: United States
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state: Arkansas
city: Chino
country: United States
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state: California
city: La Jolla
country: United States
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state: California
city: Lincoln
country: United States
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state: California
city: Modesto
country: United States
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state: California
city: Colorado Springs
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state: Colorado
city: Stamford
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state: Connecticut
city: Bradenton
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state: Florida
city: Delray Beach
country: United States
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city: Gainesville
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city: Miami Springs
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city: Miami
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city: Ocala
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city: Sanford
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city: St. Petersburg
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city: Tampa
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city: West Palm Beach
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city: Conyers
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state: Georgia
city: John's Creek
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state: Georgia
city: Peoria
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state: Illinois
city: Council Bluffs
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state: Iowa
city: Wichita
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state: Kansas
city: Baton Rouge
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state: Louisiana
city: Shreveport
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city: Baltimore
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state: Maryland
city: Chestnut Hill
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state: Massachusetts
city: Watertown
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city: Livonia
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state: Michigan
city: St. Clair Shores
country: United States
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state: Michigan
city: Florissant
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state: Missouri
city: Henderson
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city: Freehold
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city: Voorhees
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city: Willingboro
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city: Great Neck
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city: Hartsdale
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state: New York
city: North Massapequa
country: United States
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state: New York
city: Chapel Hill
country: United States
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state: North Carolina
city: Morrisville
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state: North Carolina
city: Winston-salem
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state: North Carolina
city: Bellevue
country: United States
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state: Ohio
city: Downingtown
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state: Pennsylvania
city: Jenkintown
country: United States
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Pottstown
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state: Pennsylvania
city: Anderson
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state: South Carolina
city: Myrtle Beach
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state: South Carolina
city: Chattanooga
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state: Tennessee
city: Jackson
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state: Tennessee
city: Milan
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city: Austin
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city: Houston
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city: Hurst
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state: Utah
city: Saint George
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city: West Jordan
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state: Utah
city: Antwerpen
country: Belgium
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city: Edegem
country: Belgium
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city: Leuven
country: Belgium
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city: Moerkerke
country: Belgium
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city: Mouscron
country: Belgium
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city: Roeselare
country: Belgium
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city: Bjelovar
country: Croatia
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city: Osijek
country: Croatia
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city: Susak
country: Croatia
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city: Zagreb
country: Croatia
facility: Research Site
city: Chocen
country: Czech Republic
facility: Research Site
city: Pardubice
country: Czech Republic
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city: Prague
country: Czech Republic
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city: Praha
country: Czech Republic
facility: Research Site
city: Zlin
country: Czech Republic
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Kecskemet
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Pusztaszer
country: Hungary
facility: Research Site
city: Satoraljaujhely
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
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city: Szikszo
country: Hungary
facility: Research Site
city: Urhida
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
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city: Malaga
country: Spain
facility: Research Site
state: Andalucia
city: L' Hospitalet de Llobregat
country: Spain
facility: Research Site
state: Catalu?a
city: VIC
country: Spain
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state: Catalu?a
city: Barcelona
country: Spain
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state: Cataluna
city: Centelles (barcelona)
country: Spain
facility: Research Site
state: Cataluna
city: Fuenlabrada
country: Spain
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state: Comunidad de Madrid
city: Almeria
country: Spain
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city: Lleida
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
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city: Valencia
country: Spain
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city: Valladolid
country: Spain
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city: Goteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Vallingby
country: Sweden
facility: Research Site
city: Ayrshire
country: United Kingdom
facility: Research Site
state: AYR
city: Chesterfield
country: United Kingdom
facility: Research Site
state: Derby
city: Plymouth
country: United Kingdom
facility: Research Site
state: Devon
city: London
country: United Kingdom
facility: Research Site
state: Gt Lon
city: Royton
country: United Kingdom
facility: Research Site
state: Lancashire
city: Thornton-cleveleys
country: United Kingdom
facility: Research Site
state: Lancashire
city: Norwich
country: United Kingdom
facility: Research Site
state: Norflk
city: Barry
country: United Kingdom
facility: Research Site
state: S Glam
city: Bath
country: United Kingdom
facility: Research Site
state: Somer
city: Glasgow
country: United Kingdom
facility: Research Site
state: Strath
city: Coventry
country: United Kingdom
facility: Research Site
state: Warwks
city: Derby
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Mark Sostek
role: STUDY_DIRECTOR
References:
citation: Lawson R, King F, Marsh K, Altincatal A, Cimen A. Impact of Treatment with Naloxegol for Opioid-Induced Constipation on Patients' Health State Utility. Adv Ther. 2016 Aug;33(8):1331-46. doi: 10.1007/s12325-016-0365-y. Epub 2016 Jun 24.
citation: Tack J, Lappalainen J, Diva U, Tummala R, Sostek M. Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United European Gastroenterol J. 2015 Oct;3(5):471-80. doi: 10.1177/2050640615604543.
citation: Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014 Jun 19;370(25):2387-96. doi: 10.1056/NEJMoa1310246. Epub 2014 Jun 4.