A Phase 2, Double-Blind, Multiple-Dose Escalation Study to Evaluate NKTR-118 (Oral PEG-Naloxol) in Patients With Opioid-Induced Constipation (OIC)

Study Overview
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Brief Summary
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Study (07-IN-NX003) is a Phase 2, multi-center, placebo-controlled, double-blind, randomized, dose-escalation trial. It is designed to investigate the safety, efficacy and tolerability of NKTR-118 (PEG-naloxol) in patients with opioid-induced constipation (OIC) and other clinical manifestations of opioid-induced bowel dysfunction (OBD). The objective of this study is to evaluate the safety, effectiveness and pharmacokinetics of NKTR-118 at 4 different doses.

Official Title
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A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose, Dose Escalation Study to Evaluate the Efficacy, Safety and Tolerability of NKTR-118 in Patients With Opioid-Induced Constipation (OIC)

Conditions
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Opioid Induced Constipation (OIC)

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


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: 18 years of age or older, male or female Receiving a stable opioid regimen Documented opioid-induced constipation Willingness to stop all laxatives and other bowel regimens. The use of constipation rescue medication will be allowed during the study. Main Exclusion Criteria: Life expectancy less than 6 months Active substance abuse Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea or intermittent loose stools or constipation Pregnant or breast-feeding Any receipt of an investigational medication within 30 days of screening History or presence of specific cardiac, neurologic, endocrine and/or psychiatric conditions

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>Placebo | Drug: placebo<br>* placebo, oral, once daily (QD)<br>|
| Experimental: B<br>NKTR-118 | Drug: NKTR-118<br>* 5 mg, 25 mg, 50 mg or 100 mg, oral,once daily (QD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1 | Change from baseline in SBMs/week during Week 1 was defined as SBMs/week during the first week of double-blind study medication (between Visit 4 and Visit 6) minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. An SBM was defined as a BM without the use of laxatives in the previous 24 hours as recorded in the e-diary. | Days 1 through 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in SBMs/Week Across the 28-day Double-blind Period | Change from baseline in SBMs/week across the 28-day double-blind period was calculated as SBMs/week during 28-day double-blind study treatment period minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. | Days 1 through 28 | 
| Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire | 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 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. | Days 1 through 28 | 
| Change From Baseline in Patient Assessment of Constipation-Symptoms (PAC-SYM) Questionnaire | 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 is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement. | Days 1 through 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NKTR, constipation, opioid, induced, bowel, dysfunction, Naloxol, Naloxone, Narcan, PEG naloxol, OIC, OBD, Nektar