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

NCT01384292 | Terminated Phase 3 Results

• 2 other identifiers: D3820C000062011-001985-16
• Study Type: interventional
• Target: 14
• Locations: 14 countries
• Sites: 140

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).

Conditions

Opioid-Induced Constipation

Keywords

Cancer-Related Pain; Opioid-Induced Constipation; OIC

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

1 (part A and B)

EXPERIMENTAL

Oral treatment

Drug: NKTR-118

2 (part A and B)

EXPERIMENTAL

Oral treatment

Drug: NKTR-118

3 (part A only)

PLACEBO COMPARATOR

Oral treatment

Drug: Placebo

Interventions

NKTR-118 DRUG

12.5 mg oral tablet once daily

1 (part A and B)

Placebo DRUG

Oral treatment

3 (part A only)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (140)

Research Site

Huntsville, Alabama, United States

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Casa Grande, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Fort Smith, Arkansas, United States

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Hot Springs, Arkansas, United States

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North Little Rock, Arkansas, United States

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Encino, California, United States

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Fountain Valley, California, United States

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Gilroy, California, United States

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Laguna Hills, California, United States

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Montebello, California, United States

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Orange, California, United States

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Riverside, California, United States

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San Bernardino, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Baypines, Florida, United States

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Boynton Beach, Florida, United States

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Celebration, Florida, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Lake Worth, Florida, United States

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Lakeland, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Naples, Florida, United States

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Plantation, Florida, United States

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Tavares, Florida, United States

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Albany, Georgia, United States

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Marietta, Georgia, United States

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Riverdale, Georgia, United States

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Roswell, Georgia, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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Springfield, Illinois, United States

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Anderson, Indiana, United States

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Evansville, Indiana, United States

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Owensboro, Kentucky, United States

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Lafayette, Louisiana, United States

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Elkridge, Maryland, United States

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Hollywood, Maryland, United States

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Boston, Massachusetts, United States

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Fairhaven, Massachusetts, United States

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Detroit, Michigan, United States

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Kalamazoo, Michigan, United States

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Southaven, Mississippi, United States

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Jefferson City, Missouri, United States

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St Louis, Missouri, United States

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Missoula, Montana, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Toms River, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Great Neck, New York, United States

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Syracuse, New York, United States

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Chapel Hill, North Carolina, United States

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Flat Rock, North Carolina, United States

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Morrisville, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Bismarck, North Dakota, United States

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Akron, Ohio, United States

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Beavercreek, Ohio, United States

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Cleveland, Ohio, United States

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Middleton, Ohio, United States

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Danville, Pennsylvania, United States

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East Providence, Rhode Island, United States

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Charleston, South Carolina, United States

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Chattanooga, Tennessee, United States

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Beaumont, Texas, United States

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Bellaire, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Lubbock, Texas, United States

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San Antonio, Texas, United States

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Sugarland, Texas, United States

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Fairfax, Virginia, United States

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Broadmeadow, New South Wales, Australia

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Frankston, Victoria, Australia

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Malvern, Victoria, Australia

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Parkville, Victoria, Australia

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Fremantle, Western Australia, Australia

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Edegem, Belgium, Belgium

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Mons, Belgium, Belgium

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Brussels, Belgium

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Wetteren, Belgium

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Haskovo, Bulgaria

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Pleven, Bulgaria

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Rousse, Bulgaria

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Shumen, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Zagreb, Croatia

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Benešov, Czechia

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České Budějovice, Czechia

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Prague, Czechia

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Hamburg, Hamburg, Germany

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Wiesbaden, Hesse, Germany

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Berlin, State of Berlin, Germany

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Offenbach, Germany

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Brzozów, Poland

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Bydgoszcz, Poland

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Gdansk, Poland

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Gliwice, Poland

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Poznan, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Ponce, Puerto Rico

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Craiova, Dolj, Romania

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Ploieşti, Prahova, Romania

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Baia Mare, Romania

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Brasov, Romania

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Brăila, Romania

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Bucharest, Romania

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Cluj-Napoca, Romania

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Onești, Romania

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Bardejov, Slovakia

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Bratislava, Slovakia

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Košice, Slovakia

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Prešov, Slovakia

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Port Elizabeth, Eastern Cape, South Africa

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Bloemfontein, Free State, South Africa

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Benoni, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Vereeniging, Gauteng, South Africa

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Durban, Kz-natal, South Africa

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Goodwood, W Cape, South Africa

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Seville, Andalusia, Spain

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A Coruña, Galicia, Spain

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Valencia, Valencia, Spain

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Penarth, CRF, United Kingdom

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Norwich, Norfolk, United Kingdom

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Guildford, Surrey, United Kingdom

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Chippenham, Wilts, United Kingdom

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Coventry, United Kingdom

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London, United Kingdom

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Related Links

• Clinical\_Study\_Report\_Synopsis\_D3820C00006

MeSH Terms

Conditions

Opioid-Induced Constipation; Cancer Pain

Interventions

naloxegol

Condition Hierarchy (Ancestors)

Constipation; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations

Limitations and Caveats

Due to recruitment challenges, enrollment was stopped early. 14 patients were randomized (\<5% of planned number), thus, there was insufficient data to perform the protocol-specified statistical analyses. Secondary outcome measures are not reported.

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: June 29, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: June 1, 2015
• Results First Posted: June 1, 2015

Record last verified: 2015-05

Locations

RO (8); ES (3); CZ (3); GB (6); BE (4); US (81); PL (7); PR (1); ZA (7); DE (4); CR (1); AU (5); BU (6); SL (4)