Opioid-Induced Constipation (OIC)Phase 3NCT01395524

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 Phase 3 study testing NKTR-118 in people with Opioid-Induced Constipation (OIC), run by AstraZeneca at 116 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 84 years
Conditions the study is for: Opioid-Induced Constipation (OIC)
What is being tested?: NKTR-118
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 302 participants
Where: 116 sitesin 4 countries
Study dates: Jul 2011to Sep 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 84 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

116 sites in 4 countries.

Country

City, postcode or hospital

116 sites in 4 countries

United States90 sites

Research Site
Albuquerque, New Mexico
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Anaheim, California
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Atlanta, Georgia
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Austin, Texas
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Avon, Indiana
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Beavercreek, Ohio
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Beverly Hills, California
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Biloxi, Mississippi
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Birmingham, Alabama
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Bloomington, Illinois
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Boise, Idaho
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Boynton Beach, Florida
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Brockton, Massachusetts
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Brooksville, Florida
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Burbank, California
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Calera, Alabama
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Charleston, South Carolina
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Charlotte, North Carolina
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Cincinnati, Ohio
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Clarksville, Tennessee
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Crystal River, Florida
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Cumberland, Rhode Island
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Dallas, Texas
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Decatur, Georgia
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DeLand, Florida
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Denver, Colorado
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Doral, Texas
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Evansville, Indiana
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Feasterville, Pennsylvania
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Fort Myers, Florida
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Garden Grove, California
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Glendale, Arizona
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Greensboro, North Carolina
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Greer, South Carolina
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Hialeah, Florida
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Hickory, North Carolina
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High Point, North Carolina
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Hot Springs, Arkansas
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Houston, Texas
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Huntingdon Valley, Pennsylvania
Reserach Site
Indianapolis, Indiana
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Jacksonville, Florida
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Jupiter, Florida
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Kalamazoo, Michigan
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Laguana Hills, California
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Laguna Hills, California
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Las Vegas, Nevada
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Levittown, Pennsylvania
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Long Beach, California
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Los Gatos, California
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Maitland, Florida
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Malvern, Arkansas
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Medord, Oregon
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Mesa, Arizona
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Miami, Florida
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Missoula, Montana
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Montebello, California
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Morrisville, North Carolina
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Naples, Florida
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National City, California
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New York, New York
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North Richland Hills, Texas
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Norwalk, California
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Omaha, Nebraska
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Orangeburg, South Carolina
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Orlando, Florida
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Ormond Beach, Florida
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Paramount, California
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Pembroke Pines, Florida
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Philadelphia, Pennsylvania
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Phoenix, Arizona
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Pikesville, Maryland
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Plantation, Florida
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Rockford, Illinois
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Sacramento, California
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Saint Joseph, Missouri
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Salt Lake City, Utah
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San Diego, California
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Santa Ana, California
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Spokane, Washington
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St Louis, Missouri
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Tamarac, Florida
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Tampa, Florida
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Trenton, New Jersey
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Tucson, Arizona
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Venice, Florida
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West Des Moines, Iowa
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West Palm Beach, Florida
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Winter Park, Florida
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Yardley, Pennsylvania

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Germany14 sites

Research Site
Berlin
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Celle, Lower Saxony
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Dietzenbach, Hesse
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Dresden
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Essen, North Rhine-Westphalia
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Hamburg, Free and Hanseatic City of Hamburg
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Hanover, Lower Saxony
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Hüttenberg, Hesse
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Kiel, Schleswig-Holstein
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Leipzig, Saxony
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Mainz, Rhineland-Palatinate
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Potsdam, BR
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Schwerin, Mecklenburg-Vorpommern
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Wetzlar, Hesse

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Australia8 sites

Research Site
Adelaide, South Australia
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Broadmeadow, New South Wales
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Darlinghurst, New South Wales
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Fremantle, Western Australia
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Greenslopes, Queensland
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Nedlands, Western Australia
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Port Kembla, New South Wales
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Westmead, New South Wales

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Slovakia4 sites

Research Site
Banská Bystrica
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Bratislava
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Košice
Research Site
Prešov

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About this study

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)

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.

Conditions: Opioid-Induced Constipation (OIC)
Being tested: NKTR-118, Placebo
Keywords: Non-Cancer-Related Pain, Opioid-Induced Constipation.
Medical subject headings: Opioid-Induced Constipation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NKTR-118Drug
12.5 mg oral tablet once daily
NKTR-118Drug
25 mg oral tablet once daily
PlaceboDrug
Oral tablet intake once daily

Study groups in NCT01395524
Study group	Role	What they receive
NKTR-118 12.5mg	Experimental	Not described Receives: Drug: NKTR-118
NKTR-118 25mg	Experimental	Not described Receives: Drug: NKTR-118
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Baseline (Week 0) to end of the follow-up period (Week 14)

Secondary outcomes (2)

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.
Measured: 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.
Measured: Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2011Sep 2012

First posted15 Jul 2011 (estimated)
Study startJul 2011
Primary completionSep 2012
Study completionSep 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Opioid-Induced Constipation (OIC)Studies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 302 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01395524
Sponsor's protocol ID: D3820C00007
Status last verified: Jan 2017
First submitted: 28 Jun 2011
Last updated: 23 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 28059433
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.
PubMed 27342744

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
Prevention of Opioid-induced Constipation in Patients With Advanced Cancer
Constipation, Opioid-Induced
RecruitingObservational study
Risk of Major Adverse Cardiovascular Events for Naldemedine & Other Medications for Opioid Induced Constipation
Opioid-induced Constipation
RecruitingPhase 1/2
Safety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
Opioid-Induced Constipation (OIC)
Not yet recruitingPhase 3
A Prospective, Multicenter, Randomized, Parallel-controlled, Superiority Trial
OIC
RecruitingObservational study
Naldemedine in Clinical Practice in Cancer Patients With Opioid Induced CONstipation: Clinical Outcomes and Patient Experience
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All Opioid-Induced Constipation (OIC) trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01395524
Acronym / sponsor ID: D3820C00007
Conditions: Opioid-Induced Constipation (OIC)
Keywords: Non-Cancer-Related Pain, Opioid-Induced Constipation.
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 302 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Jul 2011
Primary completion: Sep 2012 (actual)
Study completion: Sep 2012 (actual)
First posted: 15 Jul 2011 (estimated)
Results: Posted 17 Jun 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
NKTR-118 12.5mg	Experimental	Drug: NKTR-118
NKTR-118 25mg	Experimental	Drug: NKTR-118
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 84 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NKTR-11812.5 mg oral tablet once daily	Drug	NKTR-118 12.5mg
NKTR-11825 mg oral tablet once daily	Drug	NKTR-118 25mg
PlaceboOral tablet intake once daily	Drug	Placebo

Primary outcome

Incidence of Patients Experiencing at Least One Adverse Event (AE)
Time frame: Baseline (Week 0) to end of the follow-up period (Week 14)
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)
Time frame: Baseline (Week 0) to end of the follow-up period (Week 14)
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)
Time frame: Baseline (Week 0) to end of the follow-up period (Week 14)
The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated.

2 secondary outcomes

Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
Time frame: 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)
Time frame: Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)

Results and safety

Results posted to the registry on 17 Jun 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NKTR-118 12.5 mg	97	79
NKTR-118 25 mg	99	83
Placebo	106	89

Primary outcome: Incidence of Patients Experiencing at Least One Adverse Event (AE)

Time frame: Baseline (Week 0) to end of the follow-up period (Week 14). Number. Unit: Participants

Measure	NKTR-118 12.5 mg n = 94	NKTR-118 25 mg n = 97	Placebo n = 100
Value	32	40	33

Population analysed: The Safety analysis set included all patients who participated in Study D3820C00004 and received at least 1 dose of study drug in Study D3820C00007, with the exception of patients who were found to have randomized multiple times within the program at different centers.

Primary outcome: Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)

Time frame: Baseline (Week 0) to end of the follow-up period (Week 14). Number. Unit: Participants

Measure	NKTR-118 12.5 mg n = 94	NKTR-118 25 mg n = 97	Placebo n = 100
Value	4	4	3

Primary outcome: Incidence of Patients Experiencing Severe Adverse Events (SAEs)

Time frame: Baseline (Week 0) to end of the follow-up period (Week 14). Number. Unit: Participants

Measure	NKTR-118 12.5 mg n = 94	NKTR-118 25 mg n = 97	Placebo n = 100
Value	6	6	5

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NKTR-118 12.5 mg	6 of 94 (6.4%)	15 of 94 (16%)	Not reported
NKTR-118 25 mg	6 of 97 (6.2%)	27 of 97 (27.8%)	Not reported
Placebo	5 of 100 (5%)	11 of 100 (11%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28059433Webster 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.
Derived from this study: PubMed 27342744Lawson 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.
Clinical\_Study\_Report\_Synopsis\_D3820C00007Link provided by the sponsor.

Related trials for Opioid-Induced Constipation (OIC)

RecruitingPhase 4
Prevention of Opioid-induced Constipation in Patients With Advanced Cancer
Constipation, Opioid-Induced
RecruitingObservational study
Risk of Major Adverse Cardiovascular Events for Naldemedine & Other Medications for Opioid Induced Constipation
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RecruitingPhase 1/2
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Not yet recruitingPhase 3
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RecruitingObservational study
Naldemedine in Clinical Practice in Cancer Patients With Opioid Induced CONstipation: Clinical Outcomes and Patient Experience
Cancer, Opioid Induced Constipation (OIC)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark Sostek study director

AstraZeneca

116 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NKTR-118 in people with Opioid-Induced Constipation (OIC), run by AstraZeneca at 116 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 116 sites in United States, Germany, Australia, Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Patients Experiencing at Least One Adverse Event (AE) (time frame: Baseline (Week 0) to end of the follow-up period (Week 14)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01395524, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2017.