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

Purpose

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

Condition	Intervention	Phase
Opioid Induced Bowel Dysfunction	Drug: 0.1 mg of S-297995 or placebo Drug: 0.3 mg of S-297995 or placebo Drug: 1 mg of S-297995 or placebo Drug: 3 mg of S-297995 or placebo Drug: 0.03 mg of S-297995 or placebo Drug: 0.01 mg of S-297995 or placebo	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Chronic Pain

U.S. FDA Resources

Further study details as provided by Shionogi Inc.:

Primary Outcome Measures:

To evaluate the safety of single doses of oral S-297995 in subjects physically dependant on opioids. [ Time Frame: 24 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate incidence of signs and symptoms of withdrawal syndrome [ Time Frame: 24 days ] [ Designated as safety issue: No ]
To evaluate the efficacy of S-297995 on opioid-induced bowel dysfunction [ Time Frame: 17 days ] [ Designated as safety issue: No ]
To evaluate the pharmacokinetic profile of S-297995 and its metabolites with opioid treatment [ Time Frame: 4 days ] [ Designated as safety issue: No ]
To determine the optimal dose of S-297995 [ Time Frame: 24 days ] [ Designated as safety issue: No ]

Enrollment:	72
Study Start Date:	April 2010
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 Experimental drug or placebo	Drug: 0.1 mg of S-297995 or placebo One tablet of 0.1 mg of S-297995 or one tablet of placebo
Experimental: Cohort 2 Experimental drug or placebo	Drug: 0.3 mg of S-297995 or placebo Three tablets of 0.1 mg of S-297995 or three tablets of placebo
Experimental: Cohort 3 Experimental drug or placebo	Drug: 1 mg of S-297995 or placebo One tablet of 1 mg of S-297995 or one tablet of placebo
Experimental: Cohort 4 Experimental drug or placebo	Drug: 3 mg of S-297995 or placebo Three tablets of 1 mg of S-297995 or three tablets of placebo
Experimental: Cohort 5 Experimental drug or placebo	Drug: 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
Experimental: Cohort 6 Experimental drug or placebo	Drug: 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

Detailed 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

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01122030

Locations

United States, Utah
Lifetree Clinical Research
Salt Lake City, Utah, United States, 84106

Sponsors and Collaborators

Shionogi

Investigators

Study Director:

Shionogi Clinical Trials Administrator Clinical Support Help Line

Shionogi

More Information

No publications provided

Responsible Party:	Shionogi Clinical Trials Administrator, Shionogi
ClinicalTrials.gov Identifier:	NCT01122030 History of Changes
Other Study ID Numbers:	1007V9214
Study First Received:	May 10, 2010
Last Updated:	September 13, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Shionogi Inc.:

Chronic pain
Opioid physical dependence

Additional relevant MeSH terms:

Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Analgesics, Opioid
Analgesics
Sensory System Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants

ClinicalTrials.gov processed this record on May 16, 2013