Clinical trial NCT01122030: Study to Evaluate the Safety and Efficacy of Naldemedine (S-297995) for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid Induced Bowel Dysfunction
Keywords: Chronic pain
Opioid physical dependence
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2010-05-12
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the safety of single doses of oral naldemedine in adults physically dependent on opioids.

Detailed description: A single dose of naldemedine or matching placebo will be administered orally to each cohort of 12 participants (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 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of study drug on Day 15 up to Day 24.
Secondary outcomes:
measure: Change From Baseline to 24 Hours Post-dose in Number of Spontaneous Bowel Movements (SBMs) Per Day
timeFrame: Baseline (Day 1 to Day 15) and Day 15 to 16 (0 to 24 hours post-dose)
measure: Change From Baseline to 48 Hours Post-dose in the Number of SBMs Per Day
timeFrame: Baseline (Day 1 to Day 15) and Day 15 to Day 17 (0 to 48 hours post-dose)
measure: Change From Baseline to 24 Hours Post-dose in Number of Bowel Movements (BM) Per Day
timeFrame: Baseline and 24 hours post-dose
measure: Change From Baseline to 48 Hours Post-dose in Number of Bowel Movements Per Day
timeFrame: Baseline and 48 hours post-dose
measure: Change From Baseline to 24 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
timeFrame: Baseline and 24 hours post-dose
measure: Change From Baseline to 48 Hours Post-dose in Number of Complete Spontaneous Bowel Movements (CSBMs) Per Day
timeFrame: Baseline and 48 hours post-dose
measure: Time to First Spontaneous Bowel Movement
timeFrame: From first dose on Day 15 through Day 17
measure: Time to First Bowel Movement
timeFrame: From first dose on Day 15 through Day 17
measure: Time to First Complete Spontaneous Bowel Movement
timeFrame: From first dose on Day 15 through Day 17
measure: Change From Baseline in Straining During Bowel Movements
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Change From Baseline to 24 Hours Post-dose in Number of Complete Bowel Movements Per Day
timeFrame: Baseline and 24 hours post-dose
measure: Change From Baseline to 48 Hours Post-dose in Number of Complete Bowel Movements Per Day
timeFrame: Baseline and 48 hours post-dose
measure: Change From Baseline in Abdominal Bloating
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Change From Baseline in Abdominal Discomfort
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Change From Baseline in BM Consistency
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Change From Baseline in Number of False Start Bowel Movements Per Day
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Change From Baseline in the Number of Bowel Movements With No Straining Per Day
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Change From Baseline in Number of Rescue Medications Used Per Day
timeFrame: Baseline, 24 hours post-dose and 48 hours post-dose
measure: Percentage of Participants With Clinical Opiate Withdrawal Scale (COWS) Score > 8 at Any Time During the Study
timeFrame: The COWS assessments were performed at Screening, on Day 14, Day 15 (pre-dose and 1, 2, 3, 4, 5, 6 and 8 hours post-dose, and at unscheduled times as signs or symptoms indicate), on Days 16 and 17, and on Day 24/End of Study.
measure: Percentage of Participants With Webster Opiate Withdrawal Scale (WOWS) Score > 8 at Any Time During the Study
timeFrame: The WOWS assessment was performed at Screening, Day 14, Day 15 at pre-dose , and 24 and 48 hours post-dose and at the Follow-up/End of Study visit (Day 24).
measure: Maximum Observed Plasma Concentration (Cmax) of Naldemedine and Metabolite Nor-S-297995
timeFrame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
measure: Time to Maximum Observed Plasma Concentration of Naldemedine and Metabolite Nor-S-297995
timeFrame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration of Naldemedine and Metabolite Nor-S-297995
timeFrame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Naldemedine and Metabolite Nor-S-297995
timeFrame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
measure: Apparent Elimination Half-life of Naldemedine and Metabolite Nor-S-297995
timeFrame: Blood samples were collected predose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose.
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Shionogi Research Site
state: Utah
Study officials:
affiliation: Shionogi
name: Shionogi Clinical Trials Administrator Clinical Support Help Line
role: STUDY_DIRECTOR
References: