Clinical trial NCT01309841: 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: 2011-03-07
Enrollment: 652
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.
* Men and women who are between the ages of ≥18 and \<85 years.
* 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: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Calera
country: United States
facility: Research Site
state: Alabama
city: Glendale
country: United States
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state: Arizona
city: Mesa
country: United States
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state: Arizona
city: Phoenix
country: United States
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state: Arizona
city: Tucson
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state: Arizona
city: Hot Springs
country: United States
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state: Arkansas
city: Malvern
country: United States
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state: Arkansas
city: Anaheim
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state: California
city: Beverly Hills
country: United States
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state: California
city: Burbank
country: United States
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state: California
city: Garden Grove
country: United States
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state: California
city: Laguana Hills
country: United States
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state: California
city: Laguna Hills
country: United States
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state: California
city: Long Beach
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state: California
city: Los Gatos
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state: California
city: Montebello
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state: California
city: National City
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city: Norwalk
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city: Paramount
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city: Sacramento
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city: San Diego
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city: Santa Ana
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city: Denver
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state: Colorado
city: Boynton Beach
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state: Florida
city: Brooksville
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city: Deland
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city: Fort Myers
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city: Hialeah
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city: Inverness
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city: Jacksonville
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city: Jackson
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city: Jupiter
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city: Maitland
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city: Miami
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city: Naples
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city: Orlando
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city: Ormond Beach
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city: Pembroke Pines
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city: Plantation
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city: Tamarac
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state: Florida
city: Tampa
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city: Venice
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city: West Palm Beach
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city: Winter Park
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city: Atlanta
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state: Georgia
city: Decatur
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state: Georgia
city: Boise
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state: Idaho
city: Bloomington
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state: Illinois
city: Rockford
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city: Evansville
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state: Indiana
city: Greenfield
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state: Indiana
city: Indianapolis
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city: West Des Moines
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state: Iowa
city: Pikesville
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state: Maryland
city: Brockton
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state: Massachusetts
city: Kalamazoo
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state: Michigan
city: Biloxi
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state: Mississippi
city: St Joseph
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state: Missouri
city: St Louis
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city: Missoula
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state: Montana
city: Omaha
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Trenton
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state: New Jersey
city: Albuquerque
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state: New Mexico
city: New York
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state: New York
city: Charlotte
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state: North Carolina
city: Greensboro
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state: North Carolina
city: Hickory
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state: North Carolina
city: High Point
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state: North Carolina
city: Morrisville
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state: North Carolina
city: Beavercreek
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state: Ohio
city: Cincinnati
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state: Ohio
city: Medord
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state: Oregon
city: Feasterville
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state: Pennsylvania
city: Huntingdon Valley
country: United States
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state: Pennsylvania
city: Levittown
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Yardley
country: United States
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state: Pennsylvania
city: Cumberland
country: United States
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state: Rhode Island
city: Charleston
country: United States
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state: South Carolina
city: Greer
country: United States
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state: South Carolina
city: Orangeburg
country: United States
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state: South Carolina
city: Clarksville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
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state: Texas
city: Dallas
country: United States
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state: Texas
city: Doral
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: North Richland Hills
country: United States
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state: Texas
city: Salt Lake City
country: United States
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state: Utah
city: Spokane
country: United States
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state: Washington
city: Broadmeadow
country: Australia
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state: New South Wales
city: Darlinghurst
country: Australia
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state: New South Wales
city: Port Kembla
country: Australia
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state: New South Wales
city: Westmead
country: Australia
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state: New South Wales
city: Greenslopes
country: Australia
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state: Queensland
city: Adelaide
country: Australia
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state: South Australia
city: Fremantle
country: Australia
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state: Western Australia
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Berlin
country: Germany
facility: Research Site
state: BE
city: Potsdam
country: Germany
facility: Research Site
state: BR
city: Dietzenbach
country: Germany
facility: Research Site
state: HE
city: Huttenberg
country: Germany
facility: Research Site
state: HE
city: Wetzlar
country: Germany
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state: HE
city: Hamburg
country: Germany
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state: HH
city: Schwerin
country: Germany
facility: Research Site
state: MV
city: Celle
country: Germany
facility: Research Site
state: NI
city: Hannover
country: Germany
facility: Research Site
state: NI
city: Essen
country: Germany
facility: Research Site
state: NW
city: Mainz
country: Germany
facility: Research Site
state: RP
city: Kiel
country: Germany
facility: Research Site
state: SH
city: Dresden
country: Germany
facility: Research Site
state: SN
city: Leipzig
country: Germany
facility: Research Site
state: SN
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
Study officials:
affiliation: AstraZeneca Pharmaceuticals, Wilm DE
name: Mark Sostek
role: STUDY_DIRECTOR
References:
citation: Webster L, Tummala R, Diva U, Lappalainen J. A 12-week extension study to assess the safety and tolerability of naloxegol in patients with noncancer pain and opioid-induced constipation. J Opioid Manag. 2016 Nov/Dec;12(6):405-419. doi: 10.5055/jom.2016.0360.
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.