A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Study to Evaluate the Long-Term Safety of Alvimopan 0.5mg Twice Daily for 12 Months for the Treatment of Opioid-Induced Bowel Dysfunction in Adults taking Opioid Therapy for Persistent Non-Cancer Pai

• Conditions: Opioid-induced bowel dysfunction

• Registration Number: EUCTR2005-001725-28-PT
• Lead Sponsor: GlaxoSmithKline R & D Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-24
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 750

Inclusion Criteria

1. Those who understand 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.
2. Those who are a male or female aged 18 years or older at the time of the Screening Visit.
3. Those who are able to eat, drink, and take and hold down oral medications.
4. Those who are taking routine scheduled maintenance opioid therapy that meets all of the following criteria:
a. The maintenance opioid therapy is being taken for the indication of persistent non-cancer pain
b. The maintenance opioid therapy is comprised of one or more full opioid agonists
c. The maintenance opioid therapy has been dosed for at least one month prior to the Screening Visit and is expected to continue to be dosed for the duration of the study.
d. The maintenance opioid therapy route(s) of administration is enteral (oral, transmucosal, sublingual), parenteral infusion (intravenous, subcutaneous, intramuscular), transdermal, or rectal. Parenteral administration via patient-controlled analgesia (PCA) pump and intrathecal administration via pump are permitted, but only under certain circumstances.
5. Those who meet the protocol-definition of OBD
6. Those who in the investigators opinion, have bowel dysfunction that is predominantly resulting from the use of opioids
7. Those who are able and willing to refrain from using prophylactic laxatives and stool softeners from the Screening Visit to the Follow-Up Visit
8. Those who are able and willing to refrain from facilitating defecation via manual maneuvers throughout the study
9. Those who are able and willing to return for all scheduled visits, is literate and is capable of completing the paper questionnaires
10. Those who are ambulatory to the extent that they are capable of self-care and voluntary laxation.
11. If female, then the subject is currently either of:
a. non-childbearing potential, OR
b. child-bearing potential, has a negative urine B-hCG test at the Screening Visit (prior to investigational product administration), and agrees to use acceptable contraception throughout the study until the clinic follow-up 14 days after the last dose of investigational product.
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, lactating, or planning to become pregnant during the study.
2. Have (1) participated in another trial with an investigational drug within 30 days prior to the Screening Visit or (2) been randomized to investigational product in this study (SB-767905/014) anytime in the past, or (3) discontinued early from either phase 3 treatment OBD efficacy study (SB-767905/012 or SB-767905/013)
3. Taking opioids for cancer-related pain or for the management of drug addiction.
4. Taking any mixed agonist/antagonist opioid analgesics .
5. Have severe constipation that has not been appropriately managed such that the subject is at immediate risk of developing serious complications of constipation.
6. Have GI or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction.
7. Currently 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 or loose stools.
8. Has, in the investigators opinion, an uncontrolled systemic disease (e.g., hepatic, cardiovascular, renal, pulmonary, autoimmune, endocrine, metabolic, gastrointestinal, hematologic, or neurologic) that would contraindicate participation in this study.
9. Have current evidence of, or has been treated for a malignancy within the past five years (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected).
10. Have clinically significant laboratory abnormalities prior to randomization that are suggestive of hepatic dysfunction, viral hepatitis, renal impairment or suggestive of any other condition that would contraindicate participation in this study
11. Have a history within the past 2 years of alcohol, substance abuse, or psychiatric disorder likely to confound the assessment of gastrointestinal function.
12. Currently taking a concomitant medication or has any other known condition or physical examination finding that 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
Main Objective: To compare alvimopan with placebo for long-term safety and tolerability;Secondary Objective: • To compare alvimopan with placebo for constipation-related quality of life <br>• To describe the population pharmacokinetics of alvimopan and its main metabolite (SB-791399) for up to 12 months<br>• To explore the relationship between genetic variants and 1) the safety and/or tolerability of alvimopan and 2) the pharmacokinetics of alvimopan and its main metabolite<br>;Primary end point(s): Incidence of reported clinical adverse events, including serious and non-serious adverse events as well as treatment-limiting adverse events