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: NCT01309841
• Other study ID #: D3820C00004
• Secondary ID: 2011-001987-24
• Status: Completed
• Phase: Phase 3
• First received: March 4, 2011
• Last updated: May 29, 2015
• Start date: March 2011
• Est. completion date: August 2012

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationGermany: Federal Institute for Drugs and Medical DevicesSlovakia: State Institute for Drug ControlUnited 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: 652
• Est. completion date: August 2012
• Est. primary completion date: August 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.

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety 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
Oral tablet once daily

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Broadmeadow	New South Wales
Australia	Research Site	Darlinghurst	New South Wales
Australia	Research Site	Fremantle	Western Australia
Australia	Research Site	Greenslopes	Queensland
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	Port Kembla	New South Wales
Australia	Research Site	Westmead	New South Wales
Germany	Research Site	Berlin	BE
Germany	Research Site	Celle	NI
Germany	Research Site	Dietzenbach	HE
Germany	Research Site	Dresden	SN
Germany	Research Site	Essen	NW
Germany	Research Site	Hamburg	HH
Germany	Research Site	Hannover	NI
Germany	Research Site	Huttenberg	HE
Germany	Research Site	Kiel	SH
Germany	Research Site	Leipzig	SN
Germany	Research Site	Mainz	RP
Germany	Research Site	Potsdam	BR
Germany	Research Site	Schwerin	MV
Germany	Research Site	Wetzlar	HE
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Kosice
Slovakia	Research Site	Presov
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Anaheim	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Beavercreek	Ohio
United States	Research Site	Beverly Hills	California
United States	Research Site	Biloxi	Mississippi
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bloomington	Illinois
United States	Research Site	Boise	Idaho
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Brockton	Massachusetts
United States	Research Site	Brooksville	Florida
United States	Research Site	Burbank	California
United States	Research Site	Calera	Alabama
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clarksville	Tennessee
United States	Research Site	Cumberland	Rhode Island
United States	Research Site	Dallas	Texas
United States	Research Site	Decatur	Georgia
United States	Research Site	Deland	Florida
United States	Research Site	Denver	Colorado
United States	Research Site	Doral	Texas
United States	Research Site	Evansville	Indiana
United States	Research Site	Feasterville	Pennsylvania
United States	Research Site	Fort Myers	Florida
United States	Research Site	Garden Grove	California
United States	Research Site	Glendale	Arizona
United States	Research Site	Greenfield	Indiana
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greer	South Carolina
United States	Research Site	Hialeah	Florida
United States	Research Site	Hickory	North Carolina
United States	Research Site	High Point	North Carolina
United States	Research Site	Hot Springs	Arkansas
United States	Research Site	Houston	Texas
United States	Research Site	Huntingdon Valley	Pennsylvania
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Inverness	Florida
United States	Research Site	Jackson	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jupiter	Florida
United States	Research Site	Kalamazoo	Michigan
United States	Research Site	Laguana Hills	California
United States	Research Site	Laguna Hills	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Levittown	Pennsylvania
United States	Research Site	Long Beach	California
United States	Research Site	Los Gatos	California
United States	Research Site	Maitland	Florida
United States	Research Site	Malvern	Arkansas
United States	Research Site	Medord	Oregon
United States	Research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	Missoula	Montana
United States	Research Site	Montebello	California
United States	Research Site	Morrisville	North Carolina
United States	Research Site	Naples	Florida
United States	Research Site	National City	California
United States	Research Site	New York	New York
United States	Research Site	North Richland Hills	Texas
United States	Research Site	Norwalk	California
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Orlando	Florida
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Paramount	California
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pikesville	Maryland
United States	Research Site	Plantation	Florida
United States	Research Site	Rockford	Illinois
United States	Research Site	Sacramento	California
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Diego	California
United States	Research Site	Santa Ana	California
United States	Research Site	Spokane	Washington
United States	Research Site	St Joseph	Missouri
United States	Research Site	St Louis	Missouri
United States	Research Site	Tamarac	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Trenton	New Jersey
United States	Research Site	Tucson	Arizona
United States	Research Site	Venice	Florida
United States	Research Site	West Des Moines	Iowa
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Winter Park	Florida
United States	Research Site	Yardley	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Slovakia, 

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

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