Study Of Alvimopan Drug For Treatment Of Constipation Due To Prescription Pain Medication

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase IIb Study to Evaluate the Efficacy and Safety of Multiple Alvimopan Dosage Regimens for the Treatment of Opioid-Induced Bowel Dysfunction in Cancer Pain Subjects

A multicenter study to evaluate the effectiveness and safety of multiple dosage regimens of an investigational drug for the treatment of constipation due to prescription pain medication in subjects with cancer pain. The study will require five visits over a five-week period.

Study Overview

• Status: Completed
• Conditions: Constipation; Bowel Dysfunction
• Intervention / Treatment: Drug: placebo; Drug: alvimopan

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1405CUB
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • GSK Investigational Site
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • GSK Investigational Site
  • Queensland
    • Redcliffe, Queensland, Australia, 4020
      • GSK Investigational Site
    • South Brisbane, Queensland, Australia, 4101
      • GSK Investigational Site
  • South Australia
    • Daw Park, South Australia, Australia, 5041
      • GSK Investigational Site
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • GSK Investigational Site
• Canada
  • Quebec, Canada, G1R 2J6
    • GSK Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • GSK Investigational Site
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • GSK Investigational Site
  • Ontario
    • Kitchener, Ontario, Canada, N2G 1G3
      • GSK Investigational Site
    • London, Ontario, Canada, N6A 4L6
      • GSK Investigational Site
    • North Bay, Ontario, Canada, P1B 2H3
      • GSK Investigational Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • GSK Investigational Site
    • Sudbury, Ontario, Canada, P3E 5J1
      • GSK Investigational Site
  • Quebec
    • Bonaventure, Quebec, Canada, G0C 1E0
      • GSK Investigational Site
    • Chandler, Quebec, Canada, G0C 1K0
      • GSK Investigational Site
    • Levis, Quebec, Canada, G6V 3Z1
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H1T 2M4
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • GSK Investigational Site
• Czechia
  • Brno, Czechia, 625 00
    • GSK Investigational Site
  • Brno, Czechia, 656 91
    • GSK Investigational Site
  • Plzen, Czechia, 304 60
    • GSK Investigational Site
  • Praha 10, Czechia, 100 34
    • GSK Investigational Site
• Finland
  • Helsinki, Finland, 00029
    • GSK Investigational Site
• France
  • Bordeaux Cedex, France, 33076
    • GSK Investigational Site
  • Vandoeuvre-Les-Nancy, France, 54511
    • GSK Investigational Site
  • Villejuif Cedex, France, 94805
    • GSK Investigational Site
• Germany
  • Niedersachsen
    • Goettingen, Niedersachsen, Germany, 37073
      • GSK Investigational Site
    • Goslar, Niedersachsen, Germany, 38642
      • GSK Investigational Site
• Hong Kong
  • Kwun Tong, Hong Kong
    • GSK Investigational Site
  • Pokfulam, Hong Kong
    • GSK Investigational Site
  • Shatin, Hong Kong
    • GSK Investigational Site
• Hungary
  • Budapest, Hungary, 1097
    • GSK Investigational Site
  • Budapest, Hungary, 1529
    • GSK Investigational Site
  • Miskolc, Hungary, 3529
    • GSK Investigational Site
  • Zalaegerszeg-Pozva, Hungary, 8900
    • GSK Investigational Site
• India
  • Bangalore, India, 560 034
    • GSK Investigational Site
• Italy
  • Campania
    • Caserta, Campania, Italy, 81100
      • GSK Investigational Site
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
  • Emilia-Romagna
    • Forlì, Emilia-Romagna, Italy, 47100
      • GSK Investigational Site
    • Rimini, Emilia-Romagna, Italy, 47900
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • GSK Investigational Site
  • Lombardia
    • Milano, Lombardia, Italy, 20127
      • GSK Investigational Site
    • Pavia, Lombardia, Italy, 27100
      • GSK Investigational Site
  • Piemonte
    • Busca (CN), Piemonte, Italy, 12022
      • GSK Investigational Site
    • Novara, Piemonte, Italy, 28100
      • GSK Investigational Site
  • Sicilia
    • Catania, Sicilia, Italy, 95124
      • GSK Investigational Site
  • Toscana
    • Firenze, Toscana, Italy, 50139
      • GSK Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 152-703
    • GSK Investigational Site
• Netherlands
  • Leeuwarden, Netherlands, 8934 AD
    • GSK Investigational Site
• New Zealand
  • Dunedin, New Zealand, 9001
    • GSK Investigational Site
  • Hastings, New Zealand, 4201
    • GSK Investigational Site
  • Wellington, New Zealand, 6002
    • GSK Investigational Site
• Pakistan
  • Lahore, Pakistan, 54600
    • GSK Investigational Site
• Peru
  • Lima, Peru, Lima 11
    • GSK Investigational Site
  • Lima, Peru, Lima 34
    • GSK Investigational Site
• Philippines
  • Manila, Philippines, 1000
    • GSK Investigational Site
• Poland
  • Bialystok, Poland, 15-540
    • GSK Investigational Site
  • Olsztyn, Poland, 10-228
    • GSK Investigational Site
  • Otwock, Poland, 05-400
    • GSK Investigational Site
  • Poznan, Poland, 60-569
    • GSK Investigational Site
• Portugal
  • Lisboa, Portugal, 1069-166 Lisboa
    • GSK Investigational Site
  • Lisboa, Portugal, 1070
    • GSK Investigational Site
  • Lisboa, Portugal, 1800
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 127018
    • GSK Investigational Site
  • Moscow, Russian Federation, 119048
    • GSK Investigational Site
  • Moscow, Russian Federation, 117216
    • GSK Investigational Site
  • St'Petersburg, Russian Federation, 195247
    • GSK Investigational Site
• South Africa
  • Groenkloof, Pretoria, South Africa
    • GSK Investigational Site
  • Houghton, Johannesburg, South Africa, 2000
    • GSK Investigational Site
  • Kenilworth, Cape Town, South Africa, 7745
    • GSK Investigational Site
  • KwaZulu- Natal
    • Durban, KwaZulu- Natal, South Africa, 4001
      • GSK Investigational Site
• Spain
  • Alcorcon, Spain, 28922
    • GSK Investigational Site
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08023
    • GSK Investigational Site
  • Cordoba, Spain, 14004
    • GSK Investigational Site
  • Granada, Spain, 18012
    • GSK Investigational Site
  • Jaén, Spain, 23007
    • GSK Investigational Site
  • Madrid, Spain, 28006
    • GSK Investigational Site
  • Sabadell / Barcelona, Spain
    • GSK Investigational Site
  • Serra / Valencia, Spain
    • GSK Investigational Site
  • Sevilla, Spain, 41014
    • GSK Investigational Site
  • Soria, Spain, 42002
    • GSK Investigational Site
  • Valencia, Spain, 46010
    • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • GSK Investigational Site
• Thailand
  • Chiang Mai, Thailand, 50200
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • GSK Investigational Site
  • Newcastle-upon-Tyne, United Kingdom, NE4 6BE
    • GSK Investigational Site
  • Nottingham, United Kingdom, NG5 1PB
    • GSK Investigational Site
  • Sheffield, United Kingdom, S10 2JF
    • GSK Investigational Site
  • Surrey, United Kingdom, SM2 5PT
    • GSK Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85723
      • GSK Investigational Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • GSK Investigational Site
  • California
    • Duarte, California, United States, 91010
      • GSK Investigational Site
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • Fresno, California, United States, 93720
      • GSK Investigational Site
    • La Verne, California, United States, 91750
      • GSK Investigational Site
    • Los Angeles, California, United States, 90057
      • GSK Investigational Site
    • Los Gatos, California, United States, 95032
      • GSK Investigational Site
    • Modesto, California, United States, 95355
      • GSK Investigational Site
    • Sacramento, California, United States, 95819
      • GSK Investigational Site
    • San Diego, California, United States, 92103
      • GSK Investigational Site
    • San Diego, California, United States, 92120
      • GSK Investigational Site
    • Santa Monica, California, United States, 90403
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80210
      • GSK Investigational Site
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20007
      • GSK Investigational Site
    • Washington, D.C., District of Columbia, United States, 20010
      • GSK Investigational Site
  • Florida
    • Gainesville, Florida, United States, 32604
      • GSK Investigational Site
    • Inverness, Florida, United States, 34452
      • GSK Investigational Site
    • Lecanto, Florida, United States, 34461
      • GSK Investigational Site
    • Miami Shores, Florida, United States, 33138
      • GSK Investigational Site
    • New Port Richey, Florida, United States, 34653
      • GSK Investigational Site
    • New Port Richey, Florida, United States, 34652
      • GSK Investigational Site
    • Ocala, Florida, United States, 34474
      • GSK Investigational Site
    • Palm Harbor, Florida, United States, 34684
      • GSK Investigational Site
    • Stuart, Florida, United States, 34996
      • GSK Investigational Site
    • Tampa, Florida, United States, 33612-9497
      • GSK Investigational Site
    • Titusville, Florida, United States, 32796
      • GSK Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60610
      • GSK Investigational Site
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • GSK Investigational Site
  • Kansas
    • Hutchinson, Kansas, United States, 67502
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • GSK Investigational Site
    • Baltimore, Maryland, United States, 21229-5299
      • GSK Investigational Site
    • Baltimore, Maryland, United States, 21239
      • GSK Investigational Site
    • Bethesda, Maryland, United States, 20817
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • GSK Investigational Site
    • Boston, Massachusetts, United States, 02115
      • GSK Investigational Site
    • Worcester, Massachusetts, United States, 01608
      • GSK Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • GSK Investigational Site
    • Flint, Michigan, United States, 48503
      • GSK Investigational Site
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • GSK Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • GSK Investigational Site
  • New York
    • Bethpage, New York, United States, 11714
      • GSK Investigational Site
    • Huntington Station, New York, United States, 11746
      • GSK Investigational Site
    • Jamaica, New York, United States, 11432
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • GSK Investigational Site
    • Charlotte, North Carolina, United States, 28209
      • GSK Investigational Site
    • Durham, North Carolina, United States, 27710
      • GSK Investigational Site
    • Hendersonville, North Carolina, United States, 28793
      • GSK Investigational Site
    • Raleigh, North Carolina, United States, 27606
      • GSK Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • GSK Investigational Site
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • GSK Investigational Site
    • Bismarck, North Dakota, United States, 58503
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
    • Middletown, Ohio, United States, 45042
      • GSK Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • GSK Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • GSK Investigational Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • GSK Investigational Site
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
    • Webster, Texas, United States, 77598
      • GSK Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • GSK Investigational Site
    • Portsmouth, Virginia, United States, 23704
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23249
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23298-5028
      • GSK Investigational Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • GSK Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Participant is in any stage of cancer but has a minimum life expectancy of at least 3 months at the time of the Screening Visit.
• Participant is taking opioid therapy for persistent cancer pain.
• Participant meets the definition of opioid-induced bowel dysfunction as follows: Since starting opioid therapy, the subject has had decreased bowel movement (BM) frequency and at least one of the following constipation symptoms [sensation of incomplete evacuation, difficulty in expelling stool (straining), hard stools (abnormal stool consistency)].
• Participant understands the procedures, agrees to participate in the study, and has signed and dated the informed consent form prior to the initiation of any study-related activities, including discontinuation of pre-study laxative regimen or other prohibited medications.
• Participant is able and willing to comply with a daily paper diary and is capable of completing paper questionnaires at study visits.

Exclusion criteria:

• Participant is pregnant or lactating, or planning to become pregnant.
• Participant is not ambulatory.
• Participant has participated in another trial with an investigational drug (unapproved), device or procedure within 30 days of the Screening Visit.
• Participant is unable to eat, drink, take/hold down oral medications.
• Participant is taking opioids for the management of drug addiction.
• Participant is unable or unwilling to discontinue the use of and/or refrain from using laxatives of all types and formulation at the Screening Visit and throughout the entire study.
• Participant has severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation. This would include a subject who has reported no bowel movement for 7 consecutive days prior to the Screening Visit.
• Participant with gastrointestinal or pelvic disorders known to affect bowel transit, produce gastrointestinal (GI) obstruction, or contribute to bowel dysfunction.
• Participant is currently taking vinca alkyloids or plans to take vinca alkyloids during the study.
• Participant is currently undergoing abdominal radiation therapy and/or plans to undergo abdominal radiation therapy during the study.
• Participant is human immunodeficiency virus (HIV)-infected, has active hepatitis (any subtype including ongoing chronic hepatitis B), or has ever been infected with hepatitis C.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alvimopan 0.5 mg Twice Daily (BID); 0.5 milligrams (mg) of alvimopan was administered orally BID for 3 weeks.	Drug: alvimopan
Experimental: Alvimopan 1 mg Once Daily (QD); 0.5 mg of alvimopan was administered orally QD for 3 days, then 1 mg of alvimopan QD for the remaining 3 weeks. Placebo was administered orally QD to maintain the blind. A protocol amendment dropped this arm because another study had demonstrated 1 mg QD treatment to have similar efficacy but a less favorable gastrointestinal-related safety profile compared with 0.5 mg BID treatment.	Drug: placebo; Drug: alvimopan
Experimental: Alvimopan 1 mg Twice Daily (BID); 0.5 mg of alvimopan was administered orally BID for 3 days, then 1 mg of alvimopan BID for the remaining 3 weeks.	Drug: alvimopan
Placebo Comparator: Placebo; Placebo was administered orally BID for 3 weeks.	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Change in weekly SCBM frequency. A SCBM is a spontaneous and complete bowel movement, which means a bowel movement that occurs with no laxative use in the prior 24 hours and leaves the subject with the feeling of complete evacuation of the rectum.

Secondary Outcome Measures

Outcome Measure
Additional measures of Bowel movement (BM) frequency and symptoms, safety profile of the treatment regimens and any changes in pain intensity or opioid use.

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2003
• Primary Completion (Actual): May 1, 2006
• Study Completion (Actual): May 1, 2006

Study Registration Dates

• First Submitted: January 18, 2005
• First Submitted That Met QC Criteria: January 18, 2005
• First Posted (Estimate): January 19, 2005

Study Record Updates

• Last Update Posted (Actual): August 30, 2017
• Last Update Submitted That Met QC Criteria: August 29, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: constipation; bowel; cancer pain; pain medication; bowel dysfunction; OBD (Induced Bowel Dysfunction)
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Constipation; Intestinal Diseases; Gastrointestinal Agents; Alvimopan
• Other Study ID Numbers: 3753-009; 767905/008 (Other Identifier: Cubist Study Number)