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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Opioid-Induced Constipation (OIC)

Intervention / Treatment
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* Drug: NKTR-118
* Drug: NKTR-118
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-118 12.5mg<br> | Drug: NKTR-118<br>* 12.5 mg oral tablet once daily<br>|
| Experimental: NKTR-118 25mg<br> | Drug: NKTR-118<br>* 25 mg oral tablet once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral tablet intake once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Week 0) to end of the follow-up period (Week 14) | 
| 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. | Baseline (Week 0) to end of the follow-up period (Week 14) | 
| Incidence of Patients Experiencing Severe Adverse Events (SAEs) | The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated. | Baseline (Week 0) to end of the follow-up period (Week 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (prior to treatment) to last on-treatment assessment (up to Week 12) | 
| 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. | Baseline (prior to treatment) to last on-treatment assessment (up to Week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Cancer-Related Pain, Opioid-Induced Constipation.