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

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Constipation	Drug: Placebo Other Names Drug: ADL5945 0.25 mg Other Names	Phase 2

Tracking Information

First Submitted Date	January 11, 2011
Last Update Posted Date	January 05, 2016
Start Date	January 01, 2011
Actual Completion Date	August 01, 2011
Primary Completion Date	August 01, 2011
Results First Submitted Date	April 21, 2015
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment [Time Frame: Baseline, Weeks 1 through 4 of 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.

Original Primary Outcome Measures

• 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.

Current Secondary Outcome Measures

Original Secondary Outcome Measures

Study Design

Brief Title	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
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
Brief 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.
Detailed Description
Study Type	Interventional
Study Phase	Phase 2
Estimated Enrollment	81
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Conditions	Constipation
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Drug: Placebo Other Names Drug: ADL5945 0.25 mg Other Names
Study Groups/Cohorts	Placebo Each participant received 1 placebo capsule orally every day (QD) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week). ADL5945 0.25 mg During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week.
Study Arms	Experimental ADL5945 0.25 mg During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Drug : Placebo Experimental ADL5945 0.25 mg During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Drug : ADL5945 0.25 mg Placebo Comparator Placebo Each participant received 1 placebo capsule orally every day (QD) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week). Drug : Placebo

Arm	Intervention/Treatment
Experimental ADL5945 0.25 mg During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week.	Drug : Placebo
Experimental ADL5945 0.25 mg During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week.	Drug : ADL5945 0.25 mg
Placebo Comparator Placebo Each participant received 1 placebo capsule orally every day (QD) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).	Drug : Placebo

Recruitment Information

Recruitment Status:	Completed
Enrollment	81
Completion Date	August 01, 2011
Eligibility Criteria:	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
Gender	All
Age	18 Years to 75 Years
Accepts Healthy Volunteers	No
Contacts	Not Available
Listed Location Countries	United States

Administrative Information

NCT Number:	NCT01275755
Other Study ID Numbers	2402-002 45CL243
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Cubist Pharmaceuticals LLC
Collaborators	Not Available
Investigators	Not Available