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

This study has been completed.
Information provided by (Responsible Party):
AstraZeneca Identifier:
First received: March 4, 2011
Last updated: August 29, 2012
Last verified: August 2012

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).

Condition Intervention Phase
Opioid-Induced Constipation (OIC)
Drug: NKTR-118
Drug: Placebo
Phase 3

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

Resource links provided by NLM:

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The primary efficacy endpoint is response (responder/non-responder) to study drug during Weeks 1 to 12, for at least 9 out of 12 weeks, and at least 3 out of the last 4 weeks. [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Responder is defined as having at least 3 SBMs/week with at least 1 SBM/week increase over baseline.

Secondary Outcome Measures:
  • Response (responder/non-responder) to study drug in the LIR subgroup during Weeks 1 to 12, for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks. [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline.

  • Time (in hours) to first post-dose laxation without the use of rescue laxatives within the previous 24 hours. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Mean number of days per week with at least 1 SBM during Weeks 1 to 12. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 652
Study Start Date: March 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Oral treatment
Drug: NKTR-118
12.5 mg oral tablet once daily
Experimental: 2
Oral treatment
Drug: NKTR-118
25 mg oral tablet once daily
Placebo Comparator: 3
Oral treatment
Drug: Placebo
Oral tablet once daily


Ages Eligible for Study:   18 Years to 84 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01309841

  Show 117 Study Locations
Sponsors and Collaborators
Study Director: Mark Sostek AstraZeneca Pharmaceuticals, Wilm DE
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: AstraZeneca Identifier: NCT01309841     History of Changes
Other Study ID Numbers: D3820C00004, 2011-001987-24
Study First Received: March 4, 2011
Last Updated: August 29, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Germany: Federal Institute for Drugs and Medical Devices
Slovakia: State Institute for Drug Control
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Non-Cancer-Related Pain, Opioid-Induced Constipation

Additional relevant MeSH terms:
Signs and Symptoms
Signs and Symptoms, Digestive processed this record on May 26, 2015