A 12-week Extension of the Phase III Study (D3820C00004) to Assess the Effect and Safety of NKTR-118 in Patients With Non-cancer-related Pain and Opioid-induced Constipation

This study has been completed.
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: June 28, 2011
Last updated: September 28, 2012
Last verified: September 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 over a 6-month period.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled 12-Week Extension Study to Assess the Safety and Tolerability 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:
  • Incidence, nature, and intensity of adverse events (AEs), treatment-related AEs, serious adverse events (SAEs), AEs leading to discontinuation, and specific safety areas of interest. Changes in vital signs and physical examination. [ Time Frame: AEs collected throughout the study period, from 1st dose to last visit (14 wks). Vital signs collected and performed throughout the study period (14 wks), at all 5 visits. Physical examinations performed at beginning and end of the study period (14 wks). ] [ Designated as safety issue: Yes ]
  • Change from baseline in mean daily prescribed opioid dose. [ Time Frame: Will be collected throughout the study period (14 weeks) at Visits 1, 2, 3, 4 and 5. ] [ Designated as safety issue: Yes ]
  • Mean bisacodyl dose per week. [ Time Frame: Will be assessed for the following time intervals: between enrollment (Visit 1) to Week 4 (Visit 2) and Week 4 (Visit 2) to Week 12 (Visit 4). ] [ Designated as safety issue: Yes ]
  • Change from baseline in Numeric Rating Scale (NRS) pain score. [ Time Frame: Will be calculated at Weeks 4 (Visit 2), 8 (Visit 3) and 12 (Visit 4). ] [ Designated as safety issue: No ]
  • Observed and change from baseline in composite score of modified Himmelsbach scale. [ Time Frame: Will be collected at Enrollment (Visit 1) and Week 12 (Visit 4). ] [ Designated as safety issue: No ]
  • Changes in laboratory assessments (ie chemistry, hematology and urinalysis ) and electrocardiograms (ECGs). [ Time Frame: Laboratory assessments and ECGs will be collected at Enrollment (Visit 1), Week 12 (Visit 4) and Follow-up (Visit 5). Urinalysis will be performed at Enrollment (Visit 1) and Week 12 (Visit 4). ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in Patient Assessment of Constipation Symptoms (PAC-SYM) [ Time Frame: Will be collected at Enrollment (Visit 1), Week 4 (Visit )2, Week 12 (Visit 4) and Follow-up (Visit 5). ] [ Designated as safety issue: No ]
  • Change from baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) [ Time Frame: Will be collected at Enrollment (Visit 1), Week 4 (Visit )2, Week 12 (Visit 4) and Follow-up (Visit 5). ] [ Designated as safety issue: No ]

Enrollment: 633
Study Start Date: July 2011
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NKTR-118 12.5mg Drug: NKTR-118
12.5 mg oral tablet once daily
Experimental: NKTR-118 25mg Drug: NKTR-118
25 mg oral tablet once daily
Placebo Comparator: Placebo Drug: Placebo
Oral tablet intake once daily


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

Inclusion Criteria:

  • Must have completed the 12-week study D3820C00004 through Visit 8.
  • Provision of written informed consent prior to any study-specific procedures.
  • Men and women who were between the ages of >18 and <85 years at the time of the screening visit for study D3820C00004.
  • Continuing to receive 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.
  • Willingness to continue abstinence from all laxatives and other bowel regimens including prune juice and herbal products throughout this additional 12-week treatment period, and to use only bisacodyl as rescue medication if a bowel movement (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 the screening visit of study D3820C00004 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 related to the gastrointestinal tract that could impose risk to the patient.
  • Pregnancy or lactation.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01395524

  Show 116 Study Locations
Sponsors and Collaborators
Study Director: Mark Sostek AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01395524     History of Changes
Other Study ID Numbers: D3820C00007
Study First Received: June 28, 2011
Last Updated: September 28, 2012
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Germany: Federal Institute for Drugs and Medical Devices
Slovakia: State Institute for Drug Control

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

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

ClinicalTrials.gov processed this record on May 21, 2015