ABT-436 for Alcohol Dependence

NCT ID: NCT01613014

Last Updated: 2017-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-07-31

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.

Conditions

Alcohol Dependence; Alcohol Abuse; Alcohol Use Disorders; Alcoholism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sugar Pill

Matched Placebo sugar pill - target dose 2 pills BID

Group Type: PLACEBO_COMPARATOR

Matched Placebo - Sugar Pill

Intervention Type: DRUG

Target Dose - 2 pills BID

ABT-436

ABT-436 Target dose of 400 mg BID

Group Type: ACTIVE_COMPARATOR

ABT-436

Intervention Type: DRUG

Target dose - 400mg BID

Interventions

ABT-436

Target dose - 400mg BID

Intervention Type: DRUG

Matched Placebo - Sugar Pill

Target Dose - 2 pills BID

Intervention Type: DRUG

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:

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raye Litten, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Locations

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Boston Medical Center

Boston, Massachusetts, United States

Boston Medical Center

Quincy, Massachusetts, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Virginia

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

NCIG-004

Identifier Type: -

Identifier Source: org_study_id