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

This study has been completed.
Sponsor:
Collaborator:
Nektar Therapeutics
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00600119
First received: January 11, 2008
Last updated: May 28, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Opioid Induced Constipation (OIC)
Drug: placebo
Drug: NKTR-118
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose, Dose Escalation Study to Evaluate the Efficacy, Safety and Tolerability of NKTR-118 in Patients With Opioid-Induced Constipation (OIC)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 [ Time Frame: Days 1 through 7 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in SBMs/Week Across the 28-day Double-blind Period [ Time Frame: Days 1 through 28 ] [ Designated as safety issue: No ]
    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) Questionnaire [ Time Frame: Days 1 through 28 ] [ Designated as safety issue: No ]
    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) Questionnaire [ Time Frame: Days 1 through 28 ] [ Designated as safety issue: No ]
    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.


Enrollment: 207
Study Start Date: December 2007
Study Completion Date: April 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A
Placebo
Drug: placebo
placebo, oral, once daily (QD)
Experimental: B
NKTR-118
Drug: NKTR-118
5 mg, 25 mg, 50 mg or 100 mg, oral,once daily (QD)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Main 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00600119

  Show 33 Study Locations
Sponsors and Collaborators
AstraZeneca
Nektar Therapeutics
Investigators
Study Director: Mark Sostek AstraZeneca Pharmaceuticals, Wilm DE
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00600119     History of Changes
Other Study ID Numbers: 07-IN-NX003
Study First Received: January 11, 2008
Results First Received: October 13, 2014
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: BfArM
Romania: Romanian MOH

Keywords provided by AstraZeneca:
NKTR, constipation, opioid, induced, bowel, dysfunction, Naloxol, Naloxone, Narcan, PEG naloxol, OIC, OBD, Nektar

Additional relevant MeSH terms:
Constipation
Signs and Symptoms
Signs and Symptoms, Digestive

ClinicalTrials.gov processed this record on September 03, 2015