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

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)

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.

Study Overview

• Status: Completed
• Conditions: Opioid-Induced Constipation (OIC)
• Intervention / Treatment: Drug: NKTR-118; Drug: NKTR-118; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Broadmeadow, New South Wales, Australia
      • Research Site
    • Darlinghurst, New South Wales, Australia
      • Research Site
    • Port Kembla, New South Wales, Australia
      • Research Site
    • Westmead, New South Wales, Australia
      • Research Site
  • Queensland
    • Greenslopes, Queensland, Australia
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia
      • Research Site
  • Western Australia
    • Fremantle, Western Australia, Australia
      • Research Site
    • Nedlands, Western Australia, Australia
      • Research Site
• Germany
  • Berlin, Germany
    • Research Site
  • Dresden, Germany
    • Research Site
  • BR
    • Potsdam, BR, Germany
      • Research Site
  • HE
    • Dietzenbach, HE, Germany
      • Research Site
    • Huttenberg, HE, Germany
      • Research Site
    • Wetzlar, HE, Germany
      • Research Site
  • HH
    • Hamburg, HH, Germany
      • Research Site
  • MV
    • Schwerin, MV, Germany
      • Research Site
  • NI
    • Celle, NI, Germany
      • Research Site
    • Hannover, NI, Germany
      • Research Site
  • NW
    • Essen, NW, Germany
      • Research Site
  • RP
    • Mainz, RP, Germany
      • Research Site
  • SH
    • Kiel, SH, Germany
      • Research Site
  • SN
    • Leipzig, SN, Germany
      • Research Site
• Slovakia
  • Banska Bystrica, Slovakia
    • Research Site
  • Bratislava, Slovakia
    • Research Site
  • Kosice, Slovakia
    • Research Site
  • Presov, Slovakia
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
    • Calera, Alabama, United States
      • Research Site
  • Arizona
    • Glendale, Arizona, United States
      • Research Site
    • Mesa, Arizona, United States
      • Research Site
    • Phoenix, Arizona, United States
      • Research Site
    • Tucson, Arizona, United States
      • Research Site
  • Arkansas
    • Hot Springs, Arkansas, United States
      • Research Site
    • Malvern, Arkansas, United States
      • Research Site
  • California
    • Anaheim, California, United States
      • Research Site
    • Beverly Hills, California, United States
      • Research Site
    • Burbank, California, United States
      • Research Site
    • Garden Grove, California, United States
      • Research Site
    • Laguana Hills, California, United States
      • Research Site
    • Laguna Hills, California, United States
      • Research Site
    • Long Beach, California, United States
      • Research Site
    • Los Gatos, California, United States
      • Research Site
    • Montebello, California, United States
      • Research Site
    • National City, California, United States
      • Research Site
    • Norwalk, California, United States
      • Research Site
    • Paramount, California, United States
      • Research Site
    • Sacramento, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
    • Santa Ana, California, United States
      • Research Site
  • Colorado
    • Denver, Colorado, United States
      • Research Site
  • Florida
    • Boynton Beach, Florida, United States
      • Research Site
    • Brooksville, Florida, United States
      • Research Site
    • Crystal River, Florida, United States
      • Research Site
    • Deland, Florida, United States
      • Research Site
    • Fort Myers, Florida, United States
      • Research Site
    • Hialeah, Florida, United States
      • Research Site
    • Jacksonville, Florida, United States
      • Research Site
    • Jupiter, Florida, United States
      • Research Site
    • Maitland, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • Naples, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
    • Ormond Beach, Florida, United States
      • Research Site
    • Pembroke Pines, Florida, United States
      • Research Site
    • Plantation, Florida, United States
      • Research Site
    • Tamarac, Florida, United States
      • Research Site
    • Tampa, Florida, United States
      • Research Site
    • Venice, Florida, United States
      • Research Site
    • West Palm Beach, Florida, United States
      • Research Site
    • Winter Park, Florida, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
    • Decatur, Georgia, United States
      • Research Site
  • Idaho
    • Boise, Idaho, United States
      • Research Site
  • Illinois
    • Bloomington, Illinois, United States
      • Research Site
    • Rockford, Illinois, United States
      • Research Site
  • Indiana
    • Avon, Indiana, United States
      • Research Site
    • Evansville, Indiana, United States
      • Research Site
    • Indianapolis, Indiana, United States
      • Reserach Site
  • Iowa
    • West Des Moines, Iowa, United States
      • Research Site
  • Maryland
    • Pikesville, Maryland, United States
      • Research Site
  • Massachusetts
    • Brockton, Massachusetts, United States
      • Research Site
  • Michigan
    • Kalamazoo, Michigan, United States
      • Research Site
  • Mississippi
    • Biloxi, Mississippi, United States
      • Research Site
  • Missouri
    • St Joseph, Missouri, United States
      • Research Site
    • St Louis, Missouri, United States
      • Research Site
  • Montana
    • Missoula, Montana, United States
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New Jersey
    • Trenton, New Jersey, United States
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Research Site
    • Greensboro, North Carolina, United States
      • Research Site
    • Hickory, North Carolina, United States
      • Research Site
    • High Point, North Carolina, United States
      • Research Site
    • Morrisville, North Carolina, United States
      • Research Site
  • Ohio
    • Beavercreek, Ohio, United States
      • Research Site
    • Cincinnati, Ohio, United States
      • Research Site
  • Oregon
    • Medord, Oregon, United States
      • Research Site
  • Pennsylvania
    • Feasterville, Pennsylvania, United States
      • Research Site
    • Huntingdon Valley, Pennsylvania, United States
      • Research Site
    • Levittown, Pennsylvania, United States
      • Research Site
    • Philadelphia, Pennsylvania, United States
      • Research Site
    • Yardley, Pennsylvania, United States
      • Research Site
  • Rhode Island
    • Cumberland, Rhode Island, United States
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Research Site
    • Greer, South Carolina, United States
      • Research Site
    • Orangeburg, South Carolina, United States
      • Research Site
  • Tennessee
    • Clarksville, Tennessee, United States
      • Research Site
  • Texas
    • Austin, Texas, United States
      • Research Site
    • Dallas, Texas, United States
      • Research Site
    • Doral, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
    • North Richland Hills, Texas, United States
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States
      • Research Site
  • Washington
    • Spokane, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral tablet intake once daily
Experimental: NKTR-118 12.5mg	Drug: NKTR-118; 25 mg oral tablet once daily; Drug: NKTR-118; 12.5 mg oral tablet once daily
Experimental: NKTR-118 25mg	Drug: NKTR-118; 25 mg oral tablet once daily; Drug: NKTR-118; 12.5 mg oral tablet once daily

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Clinical_Study_Report_Synopsis_D3820C00007

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 28, 2011
• First Submitted That Met QC Criteria: July 14, 2011
• First Posted (Estimate): July 15, 2011

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Non-Cancer-Related Pain; Opioid-Induced Constipation.
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: D3820C00007