Evaluation of the Efficacy and Safety of ADL5945 Once Dai... | NCT01275755

ID	Type	Description	Link
45CL243	Other Identifier	Cubist Study Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	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
ADL5945 0.25 mg	Experimental	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 Drug: ADL5945 0.25 mg

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug		ADL5945 0.25 mg Placebo
ADL5945 0.25 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Eligibility Module

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

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).
FG001	ADL5945 0.25 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Each participant received 1 placebo capsule orally QD during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
BG001	ADL5945 0.25mg	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-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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00041 BG00140 BG00281

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

All participants who were randomized to study treatment and had at least 1 evaluable SBM post-dose measurement during the Double-blind Treatment Period. Last-observation-carried-forward (LOCF) was used to impute missing postbaseline values.

Posted

Mean

Standard Error

Number of SBMs/week

Baseline, Weeks 1 through 4 of treatment

ID	Title	Description
OG000	Placebo	Each participant received 1 placebo capsule orally QD during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
OG001	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-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.

Units	Counts
Participants	OG00041 OG00140

Title

Denominators

Categories

Title	Measurements
	OG0001.40± 0.26 OG0012.58± 0.34

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).			0	41	11	41
EG001	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.			1	40	10	40

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Cardiac Arrest	Cardiac disorders		Systematic Assessment	This Serious Adverse Event occurred 35 days following last dose of double-blind study medication. The participant died as a result of this SAE	EG0000 events0 affected41 at risk EG0011 events1 affected40 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected41 at risk EG0012 events2 affected40 at risk
Abdominal Pain Upper	Gastrointestinal disorders	Systematic Assessment	EG0003 events3 affected41 at risk EG0012 events2 affected40 at risk
Bronchitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected41 at risk EG0012 events2 affected40 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected41 at risk EG0012 events2 affected40 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected40 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected40 at risk
Upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected40 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected40 at risk

ID	Term
D003248	Constipation
D000079689	Opioid-Induced Constipation

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D000079524	Narcotic-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders