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.
  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: NCT01309841

  Show 117 Study Locations
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 August 02, 2015