Back to resultsA 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
Primary Purpose
Opioid-Induced Constipation (OIC)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
NKTR-118
NKTR-118
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Opioid-Induced Constipation (OIC) focused on measuring Non-Cancer-Related Pain, Opioid-Induced Constipation.
Eligibility 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.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
NKTR-118 12.5mg
NKTR-118 25mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Patients Experiencing at Least One Adverse Event (AE)
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)
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)
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)
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01395524
Brief Title
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
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-Induced Constipation (OIC)
Keywords
Non-Cancer-Related Pain, Opioid-Induced Constipation.
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
302 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NKTR-118 12.5mg
Arm Type
Experimental
Arm Title
NKTR-118 25mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
NKTR-118
Intervention Description
12.5 mg oral tablet once daily
Intervention Type
Drug
Intervention Name(s)
NKTR-118
Intervention Description
25 mg oral tablet once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral tablet intake once daily
Primary Outcome Measure Information:
Title
Incidence of Patients Experiencing at Least One Adverse Event (AE)
Description
The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated.
Time Frame
Baseline (Week 0) to end of the follow-up period (Week 14)
Title
Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
Description
The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.
Time Frame
Baseline (Week 0) to end of the follow-up period (Week 14)
Title
Incidence of Patients Experiencing Severe Adverse Events (SAEs)
Description
The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated.
Time Frame
Baseline (Week 0) to end of the follow-up period (Week 14)
Secondary Outcome Measure Information:
Title
Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
Description
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.
Time Frame
Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)
Title
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL)
Description
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.
Time Frame
Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
84 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Sostek
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
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Birmingham
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Alabama
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United States
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Calera
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Alabama
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United States
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Glendale
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Mesa
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Phoenix
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Anaheim
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Burbank
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Garden Grove
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Laguana Hills
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Laguna Hills
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Long Beach
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Los Gatos
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Montebello
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National City
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Norwalk
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Paramount
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Sacramento
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San Diego
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Santa Ana
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Denver
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Boynton Beach
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Brooksville
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Crystal River
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Deland
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Fort Myers
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Hialeah
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Jacksonville
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Maitland
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Miami
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Naples
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Orlando
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Ormond Beach
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Pembroke Pines
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Plantation
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Tamarac
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Tampa
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Venice
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West Palm Beach
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Rockford
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Avon
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Evansville
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Indianapolis
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West Des Moines
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Pikesville
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St Louis
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Missoula
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Omaha
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Las Vegas
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Trenton
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Albuquerque
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New York
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Charlotte
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Greensboro
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Hickory
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High Point
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Morrisville
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North Carolina
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Beavercreek
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Ohio
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Cincinnati
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Ohio
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Medord
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Oregon
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United States
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Feasterville
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United States
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Huntingdon Valley
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Pennsylvania
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United States
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Levittown
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Pennsylvania
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United States
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Philadelphia
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Pennsylvania
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United States
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Yardley
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Pennsylvania
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United States
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Cumberland
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Rhode Island
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United States
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Charleston
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South Carolina
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United States
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Greer
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South Carolina
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Orangeburg
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South Carolina
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Clarksville
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Tennessee
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United States
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Austin
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Dallas
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Texas
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Doral
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Texas
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Houston
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Texas
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North Richland Hills
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Salt Lake City
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Utah
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United States
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Spokane
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Washington
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United States
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Broadmeadow
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New South Wales
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Australia
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Darlinghurst
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New South Wales
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Australia
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Port Kembla
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New South Wales
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Australia
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Westmead
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New South Wales
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Australia
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Greenslopes
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Queensland
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Australia
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Adelaide
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South Australia
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Australia
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Fremantle
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Western Australia
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Australia
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Nedlands
State/Province
Western Australia
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Australia
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Potsdam
State/Province
BR
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Germany
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Dietzenbach
State/Province
HE
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Germany
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Huttenberg
State/Province
HE
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Germany
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City
Wetzlar
State/Province
HE
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Germany
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Hamburg
State/Province
HH
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Germany
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Schwerin
State/Province
MV
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Germany
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Celle
State/Province
NI
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Germany
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Hannover
State/Province
NI
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Germany
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Essen
State/Province
NW
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Germany
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Mainz
State/Province
RP
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Germany
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Kiel
State/Province
SH
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Germany
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Leipzig
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SN
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Banska Bystrica
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Slovakia
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Bratislava
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Slovakia
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City
Kosice
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Slovakia
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City
Presov
Country
Slovakia
12. IPD Sharing Statement
Citations:
PubMed Identifier
28059433
Citation
Webster L, Tummala R, Diva U, Lappalainen J. A 12-week extension study to assess the safety and tolerability of naloxegol in patients with noncancer pain and opioid-induced constipation. J Opioid Manag. 2016 Nov/Dec;12(6):405-419. doi: 10.5055/jom.2016.0360.
Results Reference
background
PubMed Identifier
27342744
Citation
Lawson R, King F, Marsh K, Altincatal A, Cimen A. Impact of Treatment with Naloxegol for Opioid-Induced Constipation on Patients' Health State Utility. Adv Ther. 2016 Aug;33(8):1331-46. doi: 10.1007/s12325-016-0365-y. Epub 2016 Jun 24.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1389&filename=Clinical_Study_Report_Synopsis_D3820C00007.pdf
Description
Clinical_Study_Report_Synopsis_D3820C00007
Learn more about this trial
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
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