Study to Evaluate the Safety and Efficacy of S-297995 for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain

Opioid Induced Bowel Dysfunction Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety and Efficacy of S-297995 for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01122030
• Other study ID #: 1007V9214
• Status: Completed
• Phase: Phase 2
• First received: May 10, 2010
• Last updated: September 13, 2011
• Start date: April 2010

Study information

• Verified date: September 2011
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Study consists of 6 treatment cohorts of 12 subjects with chronic pain, opioid-induced bowel dysfunction, and opioid physical dependence. Total duration of treatment for each subject will be up to 28 days.

Each subject will receive a single dose of study drug, administered orally in the morning of Day 15 under fasted conditions.

Cohort 1: 0.1 mg of S-297995 or placebo. Cohort 2: 0.3 mg of S-297995 or placebo. Cohort 3:

1 mg of S-297995 or placebo. Cohort 4: 3 mg of S-297995 or placebo. Cohort 5: 0.03 mg of S-297995 or placebo. Cohort 6: 0.01 mg of S-297995 or placebo.

The primary objective of the study is to evaluate the safety of single doses of oral S-297995 in subjects physically dependent on opioids

Description:

A single dose of S-297995 or matching placebo will be administered orally to each cohort of 12 subjects (9 treatments, 3 placebos) in the morning of Day 15 under fasted conditions. The first cohort will receive a 0.1 mg dose. Cohorts will continue to be enrolled at the next higher dose level until the highest dose level (3 mg) has been achieved or until the study is discontinued due to adverse events or Clinical Opioid Withdrawal Score of >8. A 0.03 mg dose will also be tested. A 0.01 mg dose will be tested if 4 or more subjects experience 1 or more bowel movements within the 24 hour period post dose in the 0.03 mg dosing cohort

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Understand and sign an informed consent form

• Males will agree to use an approved double-barrier method of contraception from Day 1 until 1 month after study completion

• Subject tests negative on urine drug test unless the subject has a prescription for the drug(s) that test positive

Exclusion Criteria:

• Subjects under opioid therapy for cancer-related pain or for the management of drug addiction

• Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea, intermittent loose stools, or constipation

• Subjects who have participated in any other investigational drug study within 30 days prior to Day 1

• Prior exposure to S-297995

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Pain
• Gastrointestinal Diseases
• Intestinal Diseases
• Opioid Induced Bowel Dysfunction

Intervention

Drug:
• 0.1 mg of S-297995 or placebo
One tablet of 0.1 mg of S-297995 or one tablet of placebo
• 0.3 mg of S-297995 or placebo
Three tablets of 0.1 mg of S-297995 or three tablets of placebo
• 1 mg of S-297995 or placebo
One tablet of 1 mg of S-297995 or one tablet of placebo
• 3 mg of S-297995 or placebo
Three tablets of 1 mg of S-297995 or three tablets of placebo
• 0.03 mg of S-297995 or placebo
Oral solution (18 ml) containing 0.03 mg of S-297995 or 18 ml of sterile water containing placebo
• 0.01 mg of S-297995 or placebo
Oral solution (6 ml) containing 0.01 mg of S-297995 or 6 ml of sterile water containing placebo

Locations

Country	Name	City	State
United States	Lifetree Clinical Research	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety of single doses of oral S-297995 in subjects physically dependant on opioids.		24 days	Yes
Secondary	To evaluate incidence of signs and symptoms of withdrawal syndrome		24 days	No
Secondary	To evaluate the efficacy of S-297995 on opioid-induced bowel dysfunction		17 days	No
Secondary	To evaluate the pharmacokinetic profile of S-297995 and its metabolites with opioid treatment		4 days	No
Secondary	To determine the optimal dose of S-297995		24 days	No