Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation

Opioid-Induced Constipation (OIC) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01323790
• Other study ID #: D3820C00005
• Secondary ID: 2011-001986-41
• Status: Completed
• Phase: Phase 3
• First received: March 24, 2011
• Last updated: June 1, 2015
• Start date: March 2011
• Est. completion date: September 2012

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCroatia: Agency for Medicinal Product and Medical DevicesHungary: National Institute of PharmacySpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 84 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Constipation
• Opioid-Induced Constipation (OIC)

Intervention

Drug:
• NKTR-118
12.5 mg oral tablet once daily
• NKTR-118
25 mg oral tablet once daily
• Placebo
Placebo to NKTR-118

Locations

Country	Name	City	State
Belgium	Research Site	Antwerpen
Belgium	Research Site	Edegem
Belgium	Research Site	Leuven
Belgium	Research Site	Moerkerke
Belgium	Research Site	Mouscron
Belgium	Research Site	Roeselare
Croatia	Research Site	Bjelovar
Croatia	Research Site	Osijek
Croatia	Research Site	Susak
Croatia	Research Site	Zagreb
Czech Republic	Research Site	Chocen
Czech Republic	Research Site	Pardubice
Czech Republic	Research Site	Prague
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Zlin
Hungary	Research Site	Baja
Hungary	Research Site	Budapest
Hungary	Research Site	Kecskemet
Hungary	Research Site	Miskolc
Hungary	Research Site	Pusztaszer
Hungary	Research Site	Satoraljaujhely
Hungary	Research Site	Szeged
Hungary	Research Site	Szikszo
Hungary	Research Site	Urhida
Hungary	Research Site	Zalaegerszeg
Spain	Research Site	Almeria
Spain	Research Site	Barcelona	Cataluna
Spain	Research Site	Centelles (barcelona)	Cataluna
Spain	Research Site	Fuenlabrada	Comunidad de Madrid
Spain	Research Site	L' Hospitalet de Llobregat	Catalu?a
Spain	Research Site	Lleida
Spain	Research Site	Madrid
Spain	Research Site	Malaga	Andalucia
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Valencia
Spain	Research Site	Valladolid
Spain	Research Site	VIC	Catalu?a
Sweden	Research Site	Goteborg
Sweden	Research Site	Lund
Sweden	Research Site	Stockholm
Sweden	Research Site	Vallingby
United Kingdom	Research Site	Ayrshire	AYR
United Kingdom	Research Site	Barry	S Glam
United Kingdom	Research Site	Bath	Somer
United Kingdom	Research Site	Chesterfield	Derby
United Kingdom	Research Site	Coventry	Warwks
United Kingdom	Research Site	Derby
United Kingdom	Research Site	Glasgow	Strath
United Kingdom	Research Site	London	Gt Lon
United Kingdom	Research Site	Norwich	Norflk
United Kingdom	Research Site	Plymouth	Devon
United Kingdom	Research Site	Royton	Lancashire
United Kingdom	Research Site	Thornton-cleveleys	Lancashire
United States	Research Site	Anderson	South Carolina
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Bellevue	Ohio
United States	Research Site	Bradenton	Florida
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chestnut Hill	Massachusetts
United States	Research Site	Chino	California
United States	Research Site	Clinton	Utah
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Conyers	Georgia
United States	Research Site	Council Bluffs	Iowa
United States	Research Site	Delray Beach	Florida
United States	Research Site	Downingtown	Pennsylvania
United States	Research Site	Florissant	Missouri
United States	Research Site	Freehold	New Jersey
United States	Research Site	Gainesville	Florida
United States	Research Site	Great Neck	New York
United States	Research Site	Hartsdale	New York
United States	Research Site	Henderson	Nevada
United States	Research Site	Houston	Texas
United States	Research Site	Hurst	Texas
United States	Research Site	Jackson	Tennessee
United States	Research Site	Jenkintown	Pennsylvania
United States	Research Site	John's Creek	Georgia
United States	Research Site	Jonesboro	Arkansas
United States	Research Site	La Jolla	California
United States	Research Site	Lincoln	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Livonia	Michigan
United States	Research Site	Marshall	Texas
United States	Research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	Miami Springs	Florida
United States	Research Site	Milan	Tennessee
United States	Research Site	Mobile	Alabama
United States	Research Site	Modesto	California
United States	Research Site	Morrisville	North Carolina
United States	Research Site	Myrtle Beach	South Carolina
United States	Research Site	North Little Rock	Arkansas
United States	Research Site	North Massapequa	New York
United States	Research Site	Ocala	Florida
United States	Research Site	Pell City	Alabama
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pottstown	Pennsylvania
United States	Research Site	Saint George	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	Sanford	Florida
United States	Research Site	Sherwood	Arkansas
United States	Research Site	Shreveport	Louisiana
United States	Research Site	St. Clair Shores	Michigan
United States	Research Site	St. Petersburg	Florida
United States	Research Site	Stamford	Connecticut
United States	Research Site	Sugarland	Texas
United States	Research Site	Sun Lakes	Arizona
United States	Research Site	Tampa	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	Voorhees	New Jersey
United States	Research Site	Watertown	Massachusetts
United States	Research Site	West Jordan	Utah
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Wichita	Kansas
United States	Research Site	Willingboro	New Jersey
United States	Research Site	Winston-salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Croatia,  Czech Republic,  Hungary,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12	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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12	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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours		12 weeks	No
Secondary	Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12		12 weeks	No
Secondary	Change From Baseline in Degree of Straining	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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Change From Baseline in Stool Consistency (Bristol Stool Scale)	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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)	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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Change From Baseline in Mean Spontaneous Bowel Movements/Week	The number of spontaneous bowel movements/week was determined from the patient's eDiary.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	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 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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)	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.	Baseline (Week 1) to end of treatment (Week 12)	No
Secondary	Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain	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.	Baseline (Week 1) to end of treatment (Week 12)	No

External Links

•   Clinical Study Protocol
•   Clinical_Study_Report_Synopsis_D3820C00005