Assessment of Efficacy and Safety 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:
NCT01309841
First received: March 4, 2011
Last updated: May 29, 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, 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:
  • Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12 [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period. An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication.


Secondary Outcome Measures:
  • Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12 [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks.

  • 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 ]
  • Change From Baseline in 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 ]
  • Change From Baseline in Degree of Straining [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    A single-item straining question was asked via the eDiary: "How much did you strain during your bowel movement?" Patients responded on a 5 point Likert scale: 1=Not at all; 2=A little bit; 3=A moderate amount; 4=A great deal; 5=An extreme amount. A negative change from baseline indicates improvement.

  • Change From Baseline in Stool Consistency (Bristol Stool Scale) [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    Patients rated stool consistency through completion of the BSS after each BM. The 7 stool types are: 1. Separate hard lumps, like nuts (hard to pass); 2. Sausage-shaped, but lumpy; 3. Like sausage, but with cracks on its surface; 4. Like a sausage or snake, smooth and soft; 5. Soft blobs with clear cut edges (passed easily); 6. Fluffy pieces with ragged edges, a mushy stool; 7. Watery, no solid pieces. A positive change from baseline indicates improvement.

  • Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement) [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    A single-item question on the completeness of evacuation, developed and validated through 1:1 interviews with OIC patients, was asked via the eDiary: "Did you feel like your bowels were completely empty after the bowel movement?" Patients provided a yes or a no response. A positive change from baseline indicates improvement.

  • Change From Baseline in Mean Spontaneous Bowel Movements/Week [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    The number of spontaneous bowel movements/week was determined from the patient's eDiary.

  • Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup [ Time Frame: Baseline (Week 1) to end of treatment (Week 12) ] [ Designated as safety issue: No ]
    Time to first post-dose laxation without the use of rescue laxatives within the last 24 hours was calculated in hours as: Date/Time of first post-dose laxation without rescue - First dose date/time.

  • Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM) [ Time Frame: Baseline (Week 1) to end of treatment (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) Satisfaction Domain [ Time Frame: Baseline (Week 1) to end of treatment (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: 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

  Eligibility

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

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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01309841

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Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Mark Sostek AstraZeneca Pharmaceuticals, Wilm DE
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01309841     History of Changes
Other Study ID Numbers: D3820C00004, 2011-001987-24
Study First Received: March 4, 2011
Results First Received: October 13, 2014
Last Updated: May 29, 2015
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:
Constipation
Signs and Symptoms
Signs and Symptoms, Digestive

ClinicalTrials.gov processed this record on September 03, 2015