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ABT-436 for Alcohol Dependence

Primary Purpose

Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ABT-436
Matched Placebo - Sugar Pill
Sponsored by
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Dependence focused on measuring Alcohol, Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders, Alcoholism

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Be at least 21 years of age and no more than 65 years of age.
  • Have a current (past 12 months) DSM-IV-TR diagnosis of alcohol dependence.
  • Be seeking treatment for alcohol dependence and desire a reduction or cessation of drinking.

Exclusion Criteria:

  • current (past 12 months) abuse or dependence on any psychoactive substance other than alcohol, caffeine and nicotine, including sedatives and hypnotics, as defined by DSM-IV-TR criteria.
  • positive urine toxicology screen performed during screening or baseline.
  • been hospitalized for alcohol intoxication delirium, alcohol withdrawal delirium, alcohol-induced persisting dementia or amnestic disorder, or have had an alcohol withdrawal seizure, alcohol-induced psychotic disorder with a primary diagnosis of alcohol dependence or a history of any seizure disorder.

  • Have any of the following, based on DSM-IV-TR criteria as assessed using the MINI:

    1. Current, past, or lifetime diagnosis of psychotic disorders (note schizophrenia is diagnosed under the psychotic disorder module of the MINI)
    2. Current or past diagnosis of bipolar disorder,
    3. Current or past year major depressive episode,
    4. Current (past 3 months) eating disorder (anorexia or bulimia), or
    5. Current (within past year) diagnosis of panic disorder with or without agoraphobia,
    6. Anti-social personality disorder.
  • Have any underlying medical condition that could exacerbate during trial participation causing hospitalization, surgery, and/or the need to use exclusionary medications to treat condition.
  • Be pregnant or breast-feeding or have plans to become pregnant at any time during the study.
  • Have a clinically significant abnormal laboratory value;
  • Hemoglobin A1c value > 7%.
  • Have a clinically significant ECG as determined by the investigator or abnormal ECG heart rate (<45 or > 100 bpm or QTc interval corrected for heart rate using the Fridericia formula (QTcF) > 450 msec.
  • Have HIV or Hepatitis A, B or C.

Sites / Locations

  • Johns Hopkins University School of Medicine
  • Boston Medical Center
  • Boston Medical Center
  • University of Pennsylvania
  • University of Virginia

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Sugar Pill

ABT-436

Arm Description

Matched Placebo sugar pill - target dose 2 pills BID

ABT-436 Target dose of 400 mg BID

Outcomes

Primary Outcome Measures

Weekly Percentage of Heaving Drinking Days
The primary objective of this study is to assess the efficacy of ABT-436 to reduce the weekly percentage of heavy drinking days (reduction in drinking) in subjects with alcohol dependence confirmed by DSM-IV-TR criteria. A "heavy drinking day" is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men. The outcome measure was averaged across weeks 2-12.

Secondary Outcome Measures

Full Information

First Posted
June 4, 2012
Last Updated
February 15, 2017
Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Collaborators
AbbVie
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1. Study Identification

Unique Protocol Identification Number
NCT01613014
Brief Title
ABT-436 for Alcohol Dependence
Official Title
A Phase 2, Double-Blind, Randomized, Placebo Controlled Trial to Assess the Efficacy of ABT-436 for Alcohol Dependence
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Collaborators
AbbVie

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary efficacy endpoint examines the hypothesis that ABT-436 will decrease the weekly percentage of heavy drinking days during Study Weeks 2 through 12 (Days 8-84) as compared to placebo. A "heavy drinking day" is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men.
Detailed Description
Adrenocorticotropic hormone (ACTH) release from the pituitary gland via V1B stimulation is central to the hypothalamus-pituitary-adrenal (HPA) axis stress response (Carrasco & Van de Kar-2003, Herman & Cullinan-1997, Sapolsky et al-2000; Tsigos & Chrousos-2002). Chronic dysregulation of the HPA axis is common in major depressive disorder, anxiety disorders, and substance abuse disorders characterized by elevated AVP, increased responsiveness to AVP, as well as either increased or decreased overall HPA axis activity or responsiveness (Dinan & Scott-2005). HPA axis normalization via pituitary V1B antagonism is a mechanism for potential ABT-436 efficacy in these disorders (Schüle et al-2009). Limbic V1B antagonism in the brain may also contribute to efficacy (Roper et al-2011). Alcohol dependence, or alcoholism, is characterized by a chronic relapsing course, in which alcohol-associated cues and stress are known relapse triggers (Brownell et al-1986, Heilig & Egli-2006, Sinha & Li-2007). Recent research suggests that neural systems mediating behavioral stress responses may offer useful targets for pharmacotherapy of alcoholism. In animal models, excessive alcohol consumption that results from a history of alcohol dependence is accompanied by increased behavioral sensitivity to stress (Heilig & Koob-2007). Preclinical studies have shown that V1B antagonists can attenuate reinstatement of heroin and alcohol self-administration, and block dependence-induced exaggeration of alcohol intake, in rats. V1B antagonists have also been shown to block stress-induced reinstatement of drug and alcohol seeking in ethanol dependent rats (Zhou-2011). For these reasons the NIAAA Clinical Investigations Group (NCIG) proposes to test ABT-436 in a Phase 2, proof of concept trial for the treatment of alcohol dependence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders, Alcoholism
Keywords
Alcohol, Alcohol Dependence, Alcohol Abuse, Alcohol Use Disorders, Alcoholism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sugar Pill
Arm Type
Placebo Comparator
Arm Description
Matched Placebo sugar pill - target dose 2 pills BID
Arm Title
ABT-436
Arm Type
Active Comparator
Arm Description
ABT-436 Target dose of 400 mg BID
Intervention Type
Drug
Intervention Name(s)
ABT-436
Intervention Description
Target dose - 400mg BID
Intervention Type
Drug
Intervention Name(s)
Matched Placebo - Sugar Pill
Intervention Description
Target Dose - 2 pills BID
Primary Outcome Measure Information:
Title
Weekly Percentage of Heaving Drinking Days
Description
The primary objective of this study is to assess the efficacy of ABT-436 to reduce the weekly percentage of heavy drinking days (reduction in drinking) in subjects with alcohol dependence confirmed by DSM-IV-TR criteria. A "heavy drinking day" is 4 or more drinks per drinking day for women and 5 or more drinks per drinking day for men. The outcome measure was averaged across weeks 2-12.
Time Frame
Weeks 2-12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be at least 21 years of age and no more than 65 years of age. Have a current (past 12 months) DSM-IV-TR diagnosis of alcohol dependence. Be seeking treatment for alcohol dependence and desire a reduction or cessation of drinking. Exclusion Criteria: current (past 12 months) abuse or dependence on any psychoactive substance other than alcohol, caffeine and nicotine, including sedatives and hypnotics, as defined by DSM-IV-TR criteria. positive urine toxicology screen performed during screening or baseline. been hospitalized for alcohol intoxication delirium, alcohol withdrawal delirium, alcohol-induced persisting dementia or amnestic disorder, or have had an alcohol withdrawal seizure, alcohol-induced psychotic disorder with a primary diagnosis of alcohol dependence or a history of any seizure disorder. Have any of the following, based on DSM-IV-TR criteria as assessed using the MINI: Current, past, or lifetime diagnosis of psychotic disorders (note schizophrenia is diagnosed under the psychotic disorder module of the MINI) Current or past diagnosis of bipolar disorder, Current or past year major depressive episode, Current (past 3 months) eating disorder (anorexia or bulimia), or Current (within past year) diagnosis of panic disorder with or without agoraphobia, Anti-social personality disorder. Have any underlying medical condition that could exacerbate during trial participation causing hospitalization, surgery, and/or the need to use exclusionary medications to treat condition. Be pregnant or breast-feeding or have plans to become pregnant at any time during the study. Have a clinically significant abnormal laboratory value; Hemoglobin A1c value > 7%. Have a clinically significant ECG as determined by the investigator or abnormal ECG heart rate (<45 or > 100 bpm or QTc interval corrected for heart rate using the Fridericia formula (QTcF) > 450 msec. Have HIV or Hepatitis A, B or C.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raye Litten, PhD
Organizational Affiliation
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Boston Medical Center
City
Quincy
State/Province
Massachusetts
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22911
Country
United States

12. IPD Sharing Statement

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ABT-436 for Alcohol Dependence

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