Evaluation of the Efficacy and Safety of ADL5945 Once Daily for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain

Constipation Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of ADL5945 Once Daily for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01275755
• Other study ID #: 2402-002
• Secondary ID: 45CL243
• Status: Completed
• Phase: Phase 2
• Start date: January 19, 2011
• Est. completion date: July 15, 2011

Study information

• Verified date: October 2018
• Source: Cubist Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Morphine and related opioid analgesics are known to slow gastrointestinal (GI) motility and reduce intestinal secretion through their binding to μ opioid receptors (MORs) within the GI tract. The most common symptoms associated with the effects of opioids are constipation and nausea and/or vomiting. Moreover, constipation is a common and distressing side effect of long-term opioid therapy.

The primary objective of this study was to compare ADL5945 once daily, a MOR antagonist, with placebo in the treatment of opioid-induced constipation (OIC) in adults taking long-term opioid therapy for chronic noncancer pain.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: July 15, 2011
• Est. primary completion date: July 15, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria

• be a man or woman aged 18 to 75 years, inclusive, at the time of screening

• have a body weight =45 kilograms (kg) and a body mass index (BMI) =40 kilograms per square meter (kg/m^2)

• be taking a stable daily dose of opioids of =30-milligrams (mg) morphine-equivalent total -daily dose for chronic noncancer pain for =30 days before screening

• have opioid-induced constipation (OIC) by history. Additionally, based on the data collected during the 1-week screening period, participants must have <3 spontaneous bowel movements (SBMs) per week and have experienced =1 other bowel movement (BM) symptom (that is, straining to pass a stool, lumpy hard stools or small pellets, or sense of incomplete evacuation after passing a stool) for =25% of the total BMs

• be willing to discontinue use of all laxatives and stool softeners during the study period except as allowed by the protocol

Key Exclusion Criteria

• be pregnant, lactating, or planning to become pregnant during the study

• have aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, or serum creatinine results =2 times the upper limit of normal

• have a recent history of myocardial infarction (MI) or unstable angina

• have an active malignancy of any type

• be taking opioids primarily for fibromyalgia

• be taking methadone as a maintenance medication (participants taking methadone for pain may be enrolled)

• be taking intrathecal opioids for the management of pain

• be taking tramadol, tapentadol, or any mixed agonist/antagonist opioid analgesics as the sole opioid for analgesia

• be taking any µ-opioid receptors (MOR) antagonist, including opioids in combination with naloxone, naltrexone, or methylnaltrexone bromide

• be taking medical marijuana

• have gastrointestinal (GI) or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction

• have taken antispasmodics, antidiarrheals, or prokinetics within 7 days before the start of the screening week

• be taking nonopioid medications known to cause constipation

• be taking antidiarrheals and have an incidence or a history of intermittent diarrhea or loose stools

• be unwilling to abstain from grapefruit and grapefruit-containing products

• have a history of alcoholism or illicit drug dependence or abuse within 5 years before screening

• have positive results on a urine drug screen (excluding opioids) that indicate illicit drug use

Related Conditions & MeSH terms

• Constipation

Intervention

Drug:
• Placebo

• ADL5945 0.25 mg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cubist Pharmaceuticals LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment	An SBM was defined as a bowel movement (BM) with no laxative use in the previous 24 hours. Each weekly SBM average was calculated as follows: (7 × number of SBMs) / (number of days with nonmissing data). The overall SBM rate for the 4-week double-blind treatment period was calculated as follows: (the average of the first week + the average of the second week + the average of the third week + the average of the fourth week) / 4.	Baseline, Weeks 1 through 4 of treatment