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.

• Conditions: Opioid-Induced Bowel Dysfunction

• Registration Number: EUCTR2005-001974-28-HU
• Lead Sponsor: GlaxoSmithKline R&D Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-15
• Last Update Posted: 15 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 195

Inclusion Criteria

1. Those who are 18 years or older at the time of the Screening Visit.
2. Those who have a minimum life expectancy greater than or equal to 3 months at the time of the Screening Visit.
3. Those who have cancer or are in remission from a recent cancer, and are taking opioid therapy for continued intractable pain. The opioid therapy must meet the following conditions:
• comprised of one or more full opioid agonists
• dosed chronically for at least one month prior to the Screening Visit at a minimum daily dose of at least 30 mg oral morphine equivalents
• maintenance opioid therapy dosed for at least one month prior to screening visit
• administered orally, transdermally, intravenously, or subcutaneously
4. Those who meet the protocol-definition of opioid-induced bowel dysfunction.
5. Those who understand the procedures, agree to participate in the study, and have 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.
6. Those who are capable of completing the Daily Diary and paper questionnaires.
7. If female, the subject is currently either of:
a) non-childbearing potential
b) child-bearing potential, has a negative serum B-hCG pregnancy test at the Screening Visit (prior to investigational product) and agrees to use acceptable contraception throughout the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant or lactating, or planning to become pregnant during the study.
2. Have participated in another trial with an investigational drug, device or procedure within 30 days prior to the Screening Visit. Subject has been randomized to investigational product in this study (SB-767905/008) or has been treated with alvimopan in another alvimopan trial at anytime in the past.
3. Unable to eat or drink. Subjects who are unable to take oral medications or to hold down oral medications due to vomiting are excluded.
4. Taking opioids for the management of drug addiction.
5. Taking opioids that are mixed agonists/antagonists or partial agonists.
6. Unable or unwilling to discontinue the use of and/or refrain from using stool softeners and laxatives of all types and formulation at the Screening Visit and throughout the Baseline and Treatment Periods. Subject is unable or unwilling to refrain from facilitating defecation via manual maneuvers (digital manipulation) throughout the study.
7. Has severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications.
8. Have GI or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction.
9. Has symptomatic primary or secondary brain tumour.
10. Currently taking vinca alkyloids or plans to take vinca alkyloids during the study.
11. In the investigators opinion has bowel dysfunction that is predominantly resulting from causes other than the chronic use of opioids.
12. Concomitant medications with known attribution to constipation are allowed if in the investigator’s opinion, the opioid therapy and not the concomitant medication is the predominant cause of the constipation.
13. Have chronic fecal incontinence.
14. Taking antidiarrheals (e.g., loperamide), has an incidence of diarrhea or loose stools in the 2 weeks prior to the Screening Visit or a history of intermittent diarrhea, loose stools or irritable bowel syndrome (IBS) symptoms which are consistent with the Rome II Criteria.
15. In the investigators opinion, has an uncontrolled systemic disease that would contraindicate participation in this study.
16. Has undergone prior radiation therapy that resulted in documented chronic radiation enteritis or radiation stricture, has undergone abdominal radiation therapy in the 2 weeks prior to the Screening Visit, is currently undergoing abdominal radiation therapy and/or plans to undergo abdominal radiation therapy during the study.
17. Have clinically significant laboratory abnormalities prior to Randomization that are suggestive of primary hepatic dysfunction or active viral hepatitis, renal impairment or any other condition that would contraindicate participation in this study.
18. Has a history of alcohol and/or substance abuse within the past 2 years.
19. Has any other known condition or physical examination finding prior to Randomization, which could contraindicate participation in this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: • To further compare the efficacy among treatment regimens<br>• To demonstrate the lack of effect of the treatment regimens on opioid analgesia<br>• To further compare the safety among the treatment regimens<br>• To quantify baseline performance status and explore the progression of cancer via the Karnofsky performance status score<br>;Primary end point(s): Changes in weekly spontaneous complete bowel movement (SCBM) frequency during the 3-week Treatment Period.;Main Objective: To identify at least one alvimopan treatment regimen that improves spontaneous complete bowel movement (SCBM) frequency compared to placebo while maintaining an acceptable tolerability profile.