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.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01395524
First received: June 28, 2011
Last updated: June 15, 2015
Last verified: May 2015
  Purpose

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 of Patients Experiencing at Least One Adverse Event (AE) [ Time Frame: Baseline (Week 0) to end of the follow-up period (Week 14) ] [ Designated as safety issue: Yes ]
    The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated.

  • Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP) [ Time Frame: Baseline (Week 0) to end of the follow-up period (Week 14) ] [ Designated as safety issue: Yes ]
    The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.

  • Incidence of Patients Experiencing Severe Adverse Events (SAEs) [ Time Frame: Baseline (Week 0) to end of the follow-up period (Week 14) ] [ Designated as safety issue: Yes ]
    The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated.


Secondary Outcome Measures:
  • Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM) [ Time Frame: Baseline (prior to treatment) to last on-treatment assessment (up to Week 12) ] [ 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 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.

  • Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) [ Time Frame: Baseline (prior to treatment) to last on-treatment assessment (up to Week 12) ] [ 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 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.


Enrollment: 302
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

  Eligibility

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

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.
  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: NCT01395524

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

Additional 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
Results First Received: October 13, 2014
Last Updated: June 15, 2015
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:
Constipation
Signs and Symptoms
Signs and Symptoms, Digestive

ClinicalTrials.gov processed this record on September 02, 2015