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

Shionogi

Status and phase: Completed; Phase 2

Conditions: Opioid Induced Bowel Dysfunction

Treatments: Drug: Placebo; Drug: Naldemedine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01122030

1007V9214

Details and patient eligibility

About

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

Full 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.

Enrollment: 72 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

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72 participants in 6 patient groups

Cohort 1

Experimental group

Description:

In this cohort 9 participants received one 0.1 mg naldemedine tablet and 3 participants received matching placebo administered on Day 15 under fasted conditions.

Treatment:

Drug: Naldemedine

Drug: Placebo

Cohort 2

Experimental group

Description:

In this cohort 9 participants received a single dose of 0.3 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions.

Treatment:

Drug: Naldemedine

Drug: Placebo

Cohort 3

Experimental group

Description:

In this cohort 9 participants received a single dose of 1 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions.

Treatment:

Drug: Naldemedine

Drug: Placebo

Cohort 4

Experimental group

Description:

In this cohort 9 participants received a single dose of 3 mg naldemedine tablets and 3 participants received matching placebo tablets administered on Day 15 under fasted conditions.

Treatment:

Drug: Naldemedine

Drug: Placebo

Cohort 5

Experimental group

Description:

In this cohort 9 participants received a single dose of 0.03 mg naldemedine oral solution and 3 participants received matching placebo oral solution administered on Day 15 under fasted conditions.

Treatment:

Drug: Naldemedine

Drug: Placebo

Cohort 6

Experimental group

Description:

In this cohort 9 participants received a single dose of 0.01 mg naldemedine oral solution and 3 participants received matching placebo oral solution administered on Day 15 under fasted conditions.

Treatment:

Drug: Naldemedine

Drug: Placebo