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Opioid-Induced Constipation (OIC)Phase 3NCT01309841

Assessment of Efficacy and Safety 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 117 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, including those patients that have inadequate response to laxative therapy (LIR). 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
652 participants
Where
117 sitesin 4 countries
Study dates
Mar 2011to Aug 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

  • Provision of written informed consent prior to any study-specific procedures.
  • Men and women who are between the ages of ≥18 and <85 years.
  • Self-reported active symptoms of OIC at screening (<3 SBMs/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 SBMs/week on average over the 2-week OIC confirmation period.
  • Receiving 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 for a minimum of 4 weeks prior to screening for non-cancer-related pain with no anticipated change in opioid dose requirement over the proposed study period as a result of disease progression.
  • Willingness to stop all laxatives and other bowel regimens including prune juice and herbal products throughout the 2-week OIC confirmation period and the 12-week treatment period, and to use only bisacodyl as rescue medication if a 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 first study visit 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 to the gastrointestinal tract that could impose a risk to the patient.
  • Pregnancy or lactation.

Trial locations and contacts

117 sites in 4 countries.

117 sites in 4 countries

United States91 sites

  • Research Site

    Albuquerque, New Mexico

  • Research Site

    Anaheim, California

  • Research Site

    Atlanta, Georgia

  • Research Site

    Austin, Texas

  • Research Site

    Beavercreek, Ohio

  • Research Site

    Beverly Hills, California

  • Research Site

    Biloxi, Mississippi

  • Research Site

    Birmingham, Alabama

  • Research Site

    Bloomington, Illinois

  • Research Site

    Boise, Idaho

  • Research Site

    Boynton Beach, Florida

  • Research Site

    Brockton, Massachusetts

  • Research Site

    Brooksville, Florida

  • Research Site

    Burbank, California

  • Research Site

    Calera, Alabama

  • Research Site

    Charleston, South Carolina

  • Research Site

    Charlotte, North Carolina

  • Research Site

    Cincinnati, Ohio

  • Research Site

    Clarksville, Tennessee

  • Research Site

    Cumberland, Rhode Island

  • Research Site

    Dallas, Texas

  • Research Site

    Decatur, Georgia

  • Research Site

    DeLand, Florida

  • Research Site

    Denver, Colorado

  • Research Site

    Doral, Texas

  • Research Site

    Evansville, Indiana

  • Research Site

    Feasterville, Pennsylvania

  • Research Site

    Fort Myers, Florida

  • Research Site

    Garden Grove, California

  • Research Site

    Glendale, Arizona

  • Research Site

    Greenfield, Indiana

  • Research Site

    Greensboro, North Carolina

  • Research Site

    Greer, South Carolina

  • Research Site

    Hialeah, Florida

  • Research Site

    Hickory, North Carolina

  • Research Site

    High Point, North Carolina

  • Research Site

    Hot Springs, Arkansas

  • Research Site

    Houston, Texas

  • Research Site

    Huntingdon Valley, Pennsylvania

  • Research Site

    Indianapolis, Indiana

  • Research Site

    Inverness, Florida

  • Research Site

    Jackson, Florida

  • Research Site

    Jacksonville, Florida

  • Research Site

    Jupiter, Florida

  • Research Site

    Kalamazoo, Michigan

  • Research Site

    Laguana Hills, California

  • Research Site

    Laguna Hills, California

  • Research Site

    Las Vegas, Nevada

  • Research Site

    Levittown, Pennsylvania

  • Research Site

    Long Beach, California

  • Research Site

    Los Gatos, California

  • Research Site

    Maitland, Florida

  • Research Site

    Malvern, Arkansas

  • Research Site

    Medord, Oregon

  • Research Site

    Mesa, Arizona

  • Research Site

    Miami, Florida

  • Research Site

    Missoula, Montana

  • Research Site

    Montebello, California

  • Research Site

    Morrisville, North Carolina

  • Research Site

    Naples, Florida

  • Research Site

    National City, California

  • Research Site

    New York, New York

  • Research Site

    North Richland Hills, Texas

  • Research Site

    Norwalk, California

  • Research Site

    Omaha, Nebraska

  • Research Site

    Orangeburg, South Carolina

  • Research Site

    Orlando, Florida

  • Research Site

    Ormond Beach, Florida

  • Research Site

    Paramount, California

  • Research Site

    Pembroke Pines, Florida

  • Research Site

    Philadelphia, Pennsylvania

  • Research Site

    Phoenix, Arizona

  • Research Site

    Pikesville, Maryland

  • Research Site

    Plantation, Florida

  • Research Site

    Rockford, Illinois

  • Research Site

    Sacramento, California

  • Research Site

    Saint Joseph, Missouri

  • Research Site

    Salt Lake City, Utah

  • Research Site

    San Diego, California

  • Research Site

    Santa Ana, California

  • Research Site

    Spokane, Washington

  • Research Site

    St Louis, Missouri

  • Research Site

    Tamarac, Florida

  • Research Site

    Tampa, Florida

  • Research Site

    Trenton, New Jersey

  • Research Site

    Tucson, Arizona

  • Research Site

    Venice, Florida

  • Research Site

    West Des Moines, Iowa

  • Research Site

    West Palm Beach, Florida

  • Research Site

    Winter Park, Florida

  • Research Site

    Yardley, Pennsylvania

Other trials in United States

Germany14 sites

  • Research Site

    Berlin, State of Berlin

  • Research Site

    Celle, Lower Saxony

  • Research Site

    Dietzenbach, Hesse

  • Research Site

    Dresden, Saxony

  • Research Site

    Essen, North Rhine-Westphalia

  • Research Site

    Hamburg, Free and Hanseatic City of Hamburg

  • Research Site

    Hanover, Lower Saxony

  • Research Site

    Hüttenberg, Hesse

  • Research Site

    Kiel, Schleswig-Holstein

  • Research Site

    Leipzig, Saxony

  • Research Site

    Mainz, Rhineland-Palatinate

  • Research Site

    Potsdam, BR

  • Research Site

    Schwerin, Mecklenburg-Vorpommern

  • Research Site

    Wetzlar, Hesse

Other trials in Germany

Australia8 sites

  • Research Site

    Adelaide, South Australia

  • Research Site

    Broadmeadow, New South Wales

  • Research Site

    Darlinghurst, New South Wales

  • Research Site

    Fremantle, Western Australia

  • Research Site

    Greenslopes, Queensland

  • Research Site

    Nedlands, Western Australia

  • Research Site

    Port Kembla, New South Wales

  • Research Site

    Westmead, New South Wales

Other trials in Australia

Slovakia4 sites

  • Research Site

    Banská Bystrica

  • Research Site

    Bratislava

  • Research Site

    Košice

  • Research Site

    Prešov

Other trials in Slovakia

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety 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, including those patients that have inadequate response to laxative therapy (LIR).

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 once daily

Study groups in NCT01309841
Study groupRoleWhat they receive
1ExperimentalOral treatment
Receives: Drug: NKTR-118
2ExperimentalOral treatment
Receives: Drug: NKTR-118
3Placebo comparatorOral treatment
Receives: Drug: Placebo

What is being measured

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

  1. Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12

    Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period. An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

Secondary outcomes (10)

  1. Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12

    Responder is defined as having at least 3 SBMs/week, with at least 1 SBM/week increase over baseline for at least 9 out of 12 weeks and at least 3 out of the last 4 weeks.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

  2. Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours

    Measured: 12 weeks

  3. Change From Baseline in Mean Number of Days Per Week With at Least 1 SBM During Weeks 1 to 12

    Measured: 12 weeks

  4. Change From Baseline in Degree of Straining

    A single-item straining question was asked via the eDiary: "How much did you strain during your bowel movement?" Patients responded on a 5 point Likert scale: 1=Not at all; 2=A little bit; 3=A moderate amount; 4=A great deal; 5=An extreme amount. A negative change from baseline indicates improvement.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

  5. Change From Baseline in Stool Consistency (Bristol Stool Scale)

    Patients rated stool consistency through completion of the BSS after each BM. The 7 stool types are: 1. Separate hard lumps, like nuts (hard to pass); 2. Sausage-shaped, but lumpy; 3. Like sausage, but with cracks on its surface; 4. Like a sausage or snake, smooth and soft; 5. Soft blobs with clear cut edges (passed easily); 6. Fluffy pieces with ragged edges, a mushy stool; 7. Watery, no solid pieces. A positive change from baseline indicates improvement.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

  6. Change From Baseline in Percent Numbers of Days With a CSBM (Complete Spontaneous Bowel Movement)

    A single-item question on the completeness of evacuation, developed and validated through 1:1 interviews with OIC patients, was asked via the eDiary: "Did you feel like your bowels were completely empty after the bowel movement?" Patients provided a yes or a no response. A positive change from baseline indicates improvement.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

  7. Change From Baseline in Mean Spontaneous Bowel Movements/Week

    The number of spontaneous bowel movements/week was determined from the patient's eDiary.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

  8. Time (in Hours) to First Post-dose Laxation Without the Use of Rescue Laxatives Within the Previous 24 Hours in the Laxative Inadequate Response (LIR) Subgroup

    Time to first post-dose laxation without the use of rescue laxatives within the last 24 hours was calculated in hours as: Date/Time of first post-dose laxation without rescue - First dose date/time.

    Measured: Baseline (Week 1) to end of treatment (Week 12)

  9. 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 (Week 1) to end of treatment (Week 12)

  10. Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL) Satisfaction Domain

    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 (Week 1) to end of treatment (Week 12)

Timeline

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

  1. First posted7 Mar 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionAug 2012
  4. Study completionAug 2012

Resources

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
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
652 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01309841
Sponsor's protocol ID
D3820C00004
Other IDs
2011-001987-24
Status last verified
May 2015
First submitted
4 Mar 2011
Last updated
1 Jun 2015
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

  • Tack J, Lappalainen J, Diva U, Tummala R, Sostek M. Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United European Gastroenterol J. 2015 Oct;3(5):471-80. doi: 10.1177/2050640615604543.

    PubMed 26535126

  • Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for opioid-induced constipation in patients with noncancer pain. N Engl J Med. 2014 Jun 19;370(25):2387-96. doi: 10.1056/NEJMoa1310246. Epub 2014 Jun 4.

    PubMed 24896818

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 117 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 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 117 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 1 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?

Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12 (time frame: Baseline (Week 1) to end of treatment (Week 12)). 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 NCT01309841, which also lists 4 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 1 Jun 2015.

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