Evaluation of the Efficacy and Safety of ADL5945 for the... | NCT01207427

ID	Type	Description	Link
45CL242	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 twice daily (BID) 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 0.1 mg	Experimental	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.	Drug: Placebo Drug: ADL5945 0.1 mg
ADL5945 0.25 mg	Experimental	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.	Drug: Placebo Drug: ADL5945 0.25 mg

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug		ADL5945 0.1 mg ADL5945 0.25 mg Placebo
ADL5945 0.1 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 for pain
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

Name	Affiliation	Role
Bruce Berger, MD	Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ADL5945 0.1 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	ADL5945 0.1 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1 mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
BG001	ADL5945 0.25 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
BG002	Placebo	Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00043 BG00145 BG00243 BG003131

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 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	ADL5945 0.1 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
OG001	ADL5945 0.25 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
OG002	Placebo	Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).

Units	Counts
Participants	OG00043 OG00145 OG00243

Title

Denominators

Categories

Title	Measurements
	OG0001.96± 0.35 OG0013.42± 0.49 OG0021.44± 0.27

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ADL5945 0.1 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1- mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.	0	43	14	43
EG001	ADL5945 0.25 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.	2	45	19	45
EG002	Placebo	Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).	0	43	15	43

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Myocardial Infarction	Cardiac disorders		Systematic Assessment		EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders		Systematic Assessment		EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Acute Coronary Syndrome	Cardiac disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Atrial Fibrillation	Cardiac disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Mitral Valve Incompetence	Cardiac disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Palpitations	Cardiac disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected43 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk
Abdominal Pain Upper	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0022 events1 affected43 at risk
Oral Discomfort	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Toothache	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Adverse Drug Reaction	General disorders	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Drug Withdrawal Syndrome	General disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Pain	General disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk
Acute Sinusitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk
Laryngitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Paronychia	Infections and infestations	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Sinusitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Tooth Infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Upper Respiratory Tract Infection	Infections and infestations	Systematic Assessment	EG0003 events3 affected43 at risk EG0015 events5 affected45 at risk EG0026 events6 affected43 at risk
Urinary Tract Infection	Infections and infestations	Systematic Assessment	EG0002 events2 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Vulvovaginal Mycotic Infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected23 at risk
Wound Infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Animal Bite	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Ankle Fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected43 at risk EG0010 events0 affected45 at risk EG0020 events0 affected43 at risk
Burns First Degree	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Road Traffic Accident	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Sunburn	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Wound Dehiscence	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Alanine Aminotransferase Increased	Investigations	Systematic Assessment	EG0002 events2 affected43 at risk EG0012 events2 affected45 at risk EG0021 events1 affected43 at risk
Aspartate Aminotransferase Increased	Investigations	Systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected45 at risk EG0021 events1 affected43 at risk
Blood Alkaline Phosphatase Increased	Investigations	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Gamma-Glutamyltransferase Increased	Investigations	Systematic Assessment	EG0002 events2 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Back Pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0002 events1 affected43 at risk EG0012 events2 affected45 at risk EG0020 events0 affected43 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0010 events0 affected45 at risk EG0021 events1 affected43 at risk
Night Sweats	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk
Hot Flush	Vascular disorders	Systematic Assessment	EG0000 events0 affected43 at risk EG0011 events1 affected45 at risk EG0020 events0 affected43 at risk

ID	Term
D000079689	Opioid-Induced Constipation
D003248	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