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Opioid-Induced Constipation (OIC)Phase 3NCT01323790

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 120 sites in 8 countries.

Completed

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

Official record
Search all trials

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
700 participants
Where
120 sitesin 8 countries
Study dates
Mar 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

  • Provision of written informed consent prior to any study-specific procedures.
  • 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

120 sites in 8 countries.

120 sites in 8 countries

United States68 sites

  • Research Site

    Anderson, South Carolina

  • Research Site

    Austin, Texas

  • Research Site

    Baltimore, Maryland

  • Research Site

    Baton Rouge, Louisiana

  • Research Site

    Bellevue, Ohio

  • Research Site

    Bradenton, Florida

  • Research Site

    Chapel Hill, North Carolina

  • Research Site

    Chattanooga, Tennessee

  • Research Site

    Chestnut Hill, Massachusetts

  • Research Site

    Chino, California

  • Research Site

    Clinton, Utah

  • Research Site

    Colorado Springs, Colorado

  • Research Site

    Conyers, Georgia

  • Research Site

    Council Bluffs, Iowa

  • Research Site

    Delray Beach, Florida

  • Research Site

    Downingtown, Pennsylvania

  • Research Site

    Florissant, Missouri

  • Research Site

    Freehold, New Jersey

  • Research Site

    Gainesville, Florida

  • Research Site

    Great Neck, New York

  • Research Site

    Hartsdale, New York

  • Research Site

    Henderson, Nevada

  • Research Site

    Houston, Texas

  • Research Site

    Hurst, Texas

  • Research Site

    Jackson, Tennessee

  • Research Site

    Jenkintown, Pennsylvania

  • Research Site

    John's Creek, Georgia

  • Research Site

    Jonesboro, Arkansas

  • Research Site

    La Jolla, California

  • Research Site

    Lincoln, California

  • Research Site

    Little Rock, Arkansas

  • Research Site

    Livonia, Michigan

  • Research Site

    Marshall, Texas

  • Research Site

    Mesa, Arizona

  • Research Site

    Miami, Florida

  • Research Site

    Miami Springs, Florida

  • Research Site

    Milan, Tennessee

  • Research Site

    Mobile, Alabama

  • Research Site

    Modesto, California

  • Research Site

    Morrisville, North Carolina

  • Research Site

    Myrtle Beach, South Carolina

  • Research Site

    North Little Rock, Arkansas

  • Research Site

    North Massapequa, New York

  • Research Site

    Ocala, Florida

  • Research Site

    Pell City, Alabama

  • Research Site

    Peoria, Illinois

  • Research Site

    Philadelphia, Pennsylvania

  • Research Site

    Phoenix, Arizona

  • Research Site

    Pottstown, Pennsylvania

  • Research Site

    Saint Clair Shores, Michigan

  • Research Site

    San Antonio, Texas

  • Research Site

    Sanford, Florida

  • Research Site

    Sherwood, Arkansas

  • Research Site

    Shreveport, Louisiana

  • Research Site

    St. George, Utah

  • Research Site

    St. Petersburg, Florida

  • Research Site

    Stamford, Connecticut

  • Research Site

    Sugarland, Texas

  • Research Site

    Sun Lakes, Arizona

  • Research Site

    Tampa, Florida

  • Research Site

    Tucson, Arizona

  • Research Site

    Voorhees Township, New Jersey

  • Research Site

    Watertown, Massachusetts

  • Research Site

    West Jordan, Utah

  • Research Site

    West Palm Beach, Florida

  • Research Site

    Wichita, Kansas

  • Research Site

    Willingboro, New Jersey

  • Research Site

    Winston-Salem, North Carolina

Other trials in United States

Spain12 sites

  • Research Site

    Almería

  • Research Site

    Barcelona, Catalonia

  • Research Site

    Centelles (barcelona), Catalonia

  • Research Site

    Fuenlabrada, Madrid

  • Research Site

    L'Hospitalet de Llobregat, Catalu?a

  • Research Site

    Lleida

  • Research Site

    Madrid

  • Research Site

    Málaga, Andalusia

  • Research Site

    Santiago de Compostela

  • Research Site

    Valencia

  • Research Site

    Valladolid

  • Research Site

    Vic, Catalu?a

Other trials in Spain

United Kingdom12 sites

  • Research Site

    Ayrshire, AYR

  • Research Site

    Barry, S Glam

  • Research Site

    Bath, Somer

  • Research Site

    Chesterfield, Derby

  • Research Site

    Coventry, Warwks

  • Research Site

    Derby, Derby

  • Research Site

    Glasgow, Strath

  • Research Site

    London, Gt Lon

  • Research Site

    Norwich, Norflk

  • Research Site

    Plymouth, Devon

  • Research Site

    Royton, Lancashire

  • Research Site

    Thornton-Cleveleys, Lancashire

Other trials in United Kingdom

Hungary10 sites

  • Research Site

    Baja

  • Research Site

    Budapest

  • Research Site

    Kecskemét

  • Research Site

    Miskolc

  • Research Site

    Pusztaszer

  • Research Site

    Sátoraljaújhely

  • Research Site

    Szeged

  • Research Site

    Szikszó

  • Research Site

    Úrhida

  • Research Site

    Zalaegerszeg

Other trials in Hungary

Belgium6 sites

  • Research Site

    Antwerp

  • Research Site

    Edegem, Belgium

  • Research Site

    Leuven

  • Research Site

    Moerkerke

  • Research Site

    Mouscron

  • Research Site

    Roeselare, Belgium

Other trials in Belgium

Croatia4 sites

  • Research Site

    Bjelovar

  • Research Site

    Osijek

  • Research Site

    Susak

  • Research Site

    Zagreb

Other trials in Croatia

Czechia4 sites

  • Research Site

    Choceň

  • Research Site

    Pardubice

  • Research Site

    Prague

  • Research Site

    Zlín

Other trials in Czechia

Sweden4 sites

  • Research Site

    Gothenburg

  • Research Site

    Lund

  • Research Site

    Stockholm

  • Research Site

    Vällingby

Other trials in Sweden

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

    Placebo to NKTR-118

Study groups in NCT01323790
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 posted28 Mar 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionSep 2012
  4. Study completionSep 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
700 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01323790
Sponsor's protocol ID
D3820C00005
Other IDs
2011-001986-41
Status last verified
May 2015
First submitted
24 Mar 2011
Last updated
2 Jun 2015
Data monitoring committee
No

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.

    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 120 sites in 8 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 4 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 2 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 120 sites in United States, Spain, United Kingdom, Hungary, Belgium and 3 more countries. 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 2 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 NCT01323790, which also lists 3 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 2 Jun 2015.

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