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A Phase 2, Double-Blind, Multiple-Dose Escalation Study to Evaluate NKTR-118 (Oral PEG-Naloxol) in Patients With Opioid-Induced Constipation (OIC)

Phase 2
Completed
Conditions
Opioid Induced Constipation (OIC)
Interventions
Drug: placebo
Registration Number
NCT00600119
Lead Sponsor
AstraZeneca
Brief Summary

Study (07-IN-NX003) is a Phase 2, multi-center, placebo-controlled, double-blind, randomized, dose-escalation trial. It is designed to investigate the safety, efficacy and tolerability of NKTR-118 (PEG-naloxol) in patients with opioid-induced constipation (OIC) and other clinical manifestations of opioid-induced bowel dysfunction (OBD). The objective of this study is to evaluate the safety, effectiveness and pharmacokinetics of NKTR-118 at 4 different doses.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
207
Inclusion Criteria
  • 18 years of age or older, male or female
  • Receiving a stable opioid regimen
  • Documented opioid-induced constipation
  • Willingness to stop all laxatives and other bowel regimens. The use of constipation rescue medication will be allowed during the study.

Main

Exclusion Criteria
  • Life expectancy less than 6 months
  • Active substance abuse
  • Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea or intermittent loose stools or constipation
  • Pregnant or breast-feeding
  • Any receipt of an investigational medication within 30 days of screening
  • History or presence of specific cardiac, neurologic, endocrine and/or psychiatric conditions

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AplaceboPlacebo
BNKTR-118NKTR-118
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1Days 1 through 7

Change from baseline in SBMs/week during Week 1 was defined as SBMs/week during the first week of double-blind study medication (between Visit 4 and Visit 6) minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. An SBM was defined as a BM without the use of laxatives in the previous 24 hours as recorded in the e-diary.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in SBMs/Week Across the 28-day Double-blind PeriodDays 1 through 28

Change from baseline in SBMs/week across the 28-day double-blind period was calculated as SBMs/week during 28-day double-blind study treatment period minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period.

Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) QuestionnaireDays 1 through 28

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 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.

Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) QuestionnaireDays 1 through 28

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 is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement.

Trial Locations

Locations (33)

Northwest Clinical Trials

🇺🇸

Boise, Idaho, United States

Investigative Clinical Research of Indiana, LLC

🇺🇸

Indianapolis, Indiana, United States

Pain & Rehabilitation Clinic of Chicago

🇺🇸

Chicago, Illinois, United States

San Diego Managed Care Group

🇺🇸

San Diego, California, United States

Riverhills Healthcare Research Division

🇺🇸

Cincinnati, Ohio, United States

Lifetree Clinical Research

🇺🇸

Salt Lake City, Utah, United States

PMI Health Research Group

🇺🇸

Atlanta, Georgia, United States

Genova Clinical Research, Inc.

🇺🇸

Tucson, Arizona, United States

Deerfoot Internal Medicine

🇺🇸

Pinson, Alabama, United States

Tennessee Valley Pain Consultants / Center for Pain Management

🇺🇸

Huntsville, Alabama, United States

Therapeutic Research Institute of Orange County

🇺🇸

Laguna Hills, California, United States

Osler Medical, Inc. / Osler Clinical Research

🇺🇸

Melbourne, Florida, United States

Millennium Pain Center

🇺🇸

Bloomington, Illinois, United States

Gulf Coast Reserach

🇺🇸

Baton Rouge, Louisiana, United States

Centennial Medical Group

🇺🇸

Elkridge, Maryland, United States

Lovelace Scientific Resources, Inc.

🇺🇸

Albuquerque, New Mexico, United States

Midwest Pharmaceutical Research, Inc.

🇺🇸

St. Peters, Missouri, United States

Gabrail Cancer Center

🇺🇸

Canton, Ohio, United States

The Center for Clinical Research, LLC

🇺🇸

Winston Salem, North Carolina, United States

ClinSearch, LLC

🇺🇸

Chattanooga, Tennessee, United States

Anderson Gastroenterology Associates, LLC

🇺🇸

Anderson, South Carolina, United States

Palm Beach Research Center

🇺🇸

West Palm Beach, Florida, United States

Gold Coast Research LLC

🇺🇸

Weston, Florida, United States

Southeast Clinical Research

🇺🇸

Chiefland, Florida, United States

MAPS Applied Research Center

🇺🇸

Edina, Minnesota, United States

Pain Treatment Center of the Bluegrass

🇺🇸

Lexington, Kentucky, United States

Arapahoe Gastroenterology, PC

🇺🇸

Littleton, Colorado, United States

Four Seasons Hospice and Palliative Care

🇺🇸

Flat Rock, North Carolina, United States

Long Island Gastrointestinal Research Group

🇺🇸

Great Neck, New York, United States

Options Health Research

🇺🇸

Tulsa, Oklahoma, United States

Medford Medical Clinic

🇺🇸

Medford, Oregon, United States

Spokane Internal Medicine

🇺🇸

Spokane, Washington, United States

Singleton Health Center

🇺🇸

Orangeburg, South Carolina, United States

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