Assessment of Efficacy and Safety in Relieving Opioid-induced Constipation in Patients With Cancer-related Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effect of NKTR-118 with placebo in the treatment of opioid-induced constipation (OIC) in patients with cancer-related pain, including those patients that have inadequate response to laxative therapy (LIR). The study consists of 2 parts; A initial 4-week treatment period (part A) and then a 12 week extension with active treatment (part B).

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NKTR-118 in Relieving Opioid-Induced Constipation (OIC) in Patients With Cancer-Related Pain

Conditions
-----------------
Opioid-Induced Constipation

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of written informed consent prior to any study-specific procedures. Men and women aged 18 or older. Histologically or cytologically confirmed neoplasm causing pain and requiring management with opioids. Self-reported active symptoms of OIC at screening (<3 RFBMs/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 RFBMs/week on average aver the 2-week OIC confirmation period. Receiving a stable maintenance opioid regimen consisting of a total daily dose of >30 mg of oral morphine, or equianalgesic amount(s) of 1 or more opioid therapies for a minimum of 4 weeks prior to screening for cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression. Exclusion Criteria: Patients receiving Opioid regimen for treatment of pain other than related to cancer. Any condition that may have affected the permeability of the blood-brain barrier, eg, known brain metastases, meningeal metastases, brain injury, multiple sclerosis, recent brain injury, uncontrolled epilepsy. Patients with cancer-related pain due to ovarian cancer, leukaemia, or lymphoma are excluded. Patients with multiple myeloma will be allowed. Patients requiring radiation therapy between the diaphragm and pelvis 4 weeks prior to Visit 1 (screening) and/or during Part A of the study are excluded. Any patients with suspected clinically relevant radiation-induced injury of small or large intestine are excluded. Pregnancy or lactation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 (part A and B)<br>Oral treatment | Drug: NKTR-118<br>* 12.5 mg oral tablet once daily<br>|
| Experimental: 2 (part A and B)<br>Oral treatment | Drug: NKTR-118<br>* 25 mg oral tablet once daily<br>|
| Placebo Comparator: 3 (part A only)<br>Oral treatment | Drug: Placebo<br>* Oral treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response (Responder/Non-responder) to Study Drug | Response (responder/non-responder) to study drug, where a responder was defined as having at least 3 rescue-free bowel movements (RFBMs) per week during the 4-week Part A treatment period, with at least 1 RFBM per week increase over baseline for at least 3 out of 4 weeks. An RFBM was defined as a bowel movement (BM) without rescue laxatives in the previous 24 hours. | Baseline to Week 4 | 

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