- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01323790
Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
June 1, 2015 updated by: AstraZeneca
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)
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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
700
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Antwerpen, Belgium
- Research Site
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Edegem, Belgium
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Leuven, Belgium
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Moerkerke, Belgium
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Mouscron, Belgium
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Roeselare, Belgium
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Bjelovar, Croatia
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Osijek, Croatia
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Susak, Croatia
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Zagreb, Croatia
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Chocen, Czech Republic
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Pardubice, Czech Republic
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Prague, Czech Republic
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Praha, Czech Republic
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Zlin, Czech Republic
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Baja, Hungary
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Budapest, Hungary
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Kecskemet, Hungary
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Miskolc, Hungary
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Pusztaszer, Hungary
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Satoraljaujhely, Hungary
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Szeged, Hungary
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Szikszo, Hungary
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Urhida, Hungary
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Zalaegerszeg, Hungary
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Almeria, Spain
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Lleida, Spain
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Madrid, Spain
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Santiago de Compostela, Spain
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Valencia, Spain
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Valladolid, Spain
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Andalucia
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Malaga, Andalucia, Spain
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Catalu?a
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L' Hospitalet de Llobregat, Catalu?a, Spain
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VIC, Catalu?a, Spain
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Cataluna
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Barcelona, Cataluna, Spain
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Centelles (barcelona), Cataluna, Spain
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Comunidad de Madrid
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Fuenlabrada, Comunidad de Madrid, Spain
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Goteborg, Sweden
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Lund, Sweden
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Stockholm, Sweden
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Vallingby, Sweden
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Derby, United Kingdom
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AYR
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Ayrshire, AYR, United Kingdom
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Derby
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Chesterfield, Derby, United Kingdom
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Devon
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Plymouth, Devon, United Kingdom
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Gt Lon
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London, Gt Lon, United Kingdom
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Lancashire
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Royton, Lancashire, United Kingdom
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Thornton-cleveleys, Lancashire, United Kingdom
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Norflk
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Norwich, Norflk, United Kingdom
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S Glam
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Barry, S Glam, United Kingdom
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Somer
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Bath, Somer, United Kingdom
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Strath
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Glasgow, Strath, United Kingdom
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Warwks
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Coventry, Warwks, United Kingdom
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Alabama
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Mobile, Alabama, United States
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Pell City, Alabama, United States
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Arizona
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Mesa, Arizona, United States
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Phoenix, Arizona, United States
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Sun Lakes, Arizona, United States
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Tucson, Arizona, United States
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Arkansas
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Jonesboro, Arkansas, United States
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Little Rock, Arkansas, United States
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North Little Rock, Arkansas, United States
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Sherwood, Arkansas, United States
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California
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Chino, California, United States
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La Jolla, California, United States
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Lincoln, California, United States
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Modesto, California, United States
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Colorado
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Colorado Springs, Colorado, United States
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Connecticut
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Stamford, Connecticut, United States
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Florida
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Bradenton, Florida, United States
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Delray Beach, Florida, United States
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Gainesville, Florida, United States
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Miami, Florida, United States
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Miami Springs, Florida, United States
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Ocala, Florida, United States
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Sanford, Florida, United States
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St. Petersburg, Florida, United States
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Tampa, Florida, United States
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West Palm Beach, Florida, United States
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Georgia
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Conyers, Georgia, United States
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John's Creek, Georgia, United States
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Illinois
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Peoria, Illinois, United States
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Iowa
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Council Bluffs, Iowa, United States
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Kansas
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Wichita, Kansas, United States
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Louisiana
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Baton Rouge, Louisiana, United States
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Shreveport, Louisiana, United States
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Maryland
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Baltimore, Maryland, United States
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Massachusetts
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Chestnut Hill, Massachusetts, United States
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Watertown, Massachusetts, United States
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Michigan
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Livonia, Michigan, United States
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St. Clair Shores, Michigan, United States
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Missouri
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Florissant, Missouri, United States
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Nevada
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Henderson, Nevada, United States
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New Jersey
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Freehold, New Jersey, United States
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Voorhees, New Jersey, United States
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Willingboro, New Jersey, United States
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New York
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Great Neck, New York, United States
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Hartsdale, New York, United States
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North Massapequa, New York, United States
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North Carolina
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Chapel Hill, North Carolina, United States
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Morrisville, North Carolina, United States
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Winston-salem, North Carolina, United States
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Ohio
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Bellevue, Ohio, United States
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Pennsylvania
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Downingtown, Pennsylvania, United States
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Jenkintown, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Pottstown, Pennsylvania, United States
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South Carolina
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Anderson, South Carolina, United States
- Research Site
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Myrtle Beach, South Carolina, United States
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Tennessee
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Chattanooga, Tennessee, United States
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Jackson, Tennessee, United States
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Milan, Tennessee, United States
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Texas
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Austin, Texas, United States
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Houston, Texas, United States
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Hurst, Texas, United States
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Marshall, Texas, United States
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San Antonio, Texas, United States
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Sugarland, Texas, United States
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Utah
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Clinton, Utah, United States
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Saint George, Utah, United States
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West Jordan, Utah, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 84 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1
Oral treatment
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25 mg oral tablet once daily
12.5 mg oral tablet once daily
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Experimental: 2
Oral treatment
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25 mg oral tablet once daily
12.5 mg oral tablet once daily
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Placebo Comparator: 3
Oral treatment
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Placebo to NKTR-118
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period.
An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication.
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Baseline (Week 1) to end of treatment (Week 12)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks.
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Baseline (Week 1) to end of treatment (Week 12)
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Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours
Time Frame: 12 weeks
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12 weeks
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Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12
Time Frame: 12 weeks
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12 weeks
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Change From Baseline in Degree of Straining
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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A single-item straining question was asked via the eDiary: "How much did you strain during your bowel movement?"
Patients responded on a 5 point Likert scale: 1=Not at all; 2=A little bit; 3=A moderate amount; 4=A great deal; 5=An extreme amount.
A negative change from baseline indicates improvement.
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Baseline (Week 1) to end of treatment (Week 12)
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Change From Baseline in Stool Consistency (Bristol Stool Scale)
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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Patients rated stool consistency through completion of the BSS after each BM.
The 7 stool types are: 1. Separate hard lumps, like nuts (hard to pass); 2. Sausage-shaped, but lumpy; 3. Like sausage, but with cracks on its surface; 4. Like a sausage or snake, smooth and soft; 5. Soft blobs with clear cut edges (passed easily); 6. Fluffy pieces with ragged edges, a mushy stool; 7. Watery, no solid pieces.
A positive change from baseline indicates improvement.
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Baseline (Week 1) to end of treatment (Week 12)
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Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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A single-item question on the completeness of evacuation, developed and validated through 1:1 interviews with OIC patients, was asked via the eDiary: "Did you feel like your bowels were completely empty after the bowel movement?"
Patients provided a yes or a no response.
A positive change from baseline indicates improvement.
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Baseline (Week 1) to end of treatment (Week 12)
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Change From Baseline in Mean Spontaneous Bowel Movements/Week
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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The number of spontaneous bowel movements/week was determined from the patient's eDiary.
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Baseline (Week 1) to end of treatment (Week 12)
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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
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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Time to first post-dose laxation without the use of rescue laxatives within the last 24 hours was calculated in hours as: Date/Time of first post-dose laxation without rescue - First dose date/time.
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Baseline (Week 1) to end of treatment (Week 12)
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Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe) in the 2 weeks (14 days) prior to assessment.
Each domain score is the mean of the non-missing items for that domain.
The total score is the mean of all non-missing items (ie, symptoms).
The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item).
A negative change from baseline indicates improvement.
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Baseline (Week 1) to end of treatment (Week 12)
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Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain
Time Frame: Baseline (Week 1) to end of treatment (Week 12)
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The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment.
Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely).
The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items).
Each domain score is the mean of the non-missing items for that domain.
The total score is the mean of all non-missing items.
The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item).
A negative change from baseline indicates improvement.
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Baseline (Week 1) to end of treatment (Week 12)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2011
Primary Completion (Actual)
September 1, 2012
Study Completion (Actual)
September 1, 2012
Study Registration Dates
First Submitted
March 24, 2011
First Submitted That Met QC Criteria
March 25, 2011
First Posted (Estimate)
March 28, 2011
Study Record Updates
Last Update Posted (Estimate)
June 2, 2015
Last Update Submitted That Met QC Criteria
June 1, 2015
Last Verified
May 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D3820C00005
- 2011-001986-41 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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AstraZenecaNektar TherapeuticsCompletedOpioid Induced Constipation (OIC)United States
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ShionogiRecruitingOpioid-Induced Constipation (OIC)France
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Theravance BiopharmaCompletedOpioid-induced Constipation (OIC)United States
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Methodist Health SystemWithdrawn
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Amsterdam UMC, location VUmcRadboud University Medical Center; University Medical Center Groningen; UMC Utrecht and other collaboratorsRecruitingConstipation, Opioid-InducedNetherlands
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-
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AstraZenecaCompletedOpioid-Induced Constipation (OIC)United States, Germany, Australia, Slovakia
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AstraZenecaNektar TherapeuticsCompletedOpioid Induced Constipation (OIC)United States
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AstraZenecaCompletedHepatic; Functional DisturbanceUnited States
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