Clinical trial NCT00764660: Trial Investigating the Efficacy and Safety of SCH 900435 (Org 25935) in Relapse Prevention in Participants With Alcohol Dependence (P05718)
Official title: A Prospective, Double-Blind, Placebo-Controlled Trial Investigating the Efficacy and Safety of SCH 900435 (Org 25935) in Relapse Prevention in Subjects With Alcohol Dependence.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alcoholism
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-10-02
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effects of SCH 900435 (Org 25935, MK-8435) on heavy drinking, safety and tolerability of SCH 900435 in participants with alcohol dependence.


Eligibility criteria: Inclusion Criteria:

* Provide written informed consent after the scope and nature of the investigation, have been explained to the participant before screening;
* Diagnosis of alcohol dependence - meeting at least 5 out of 7 criteria according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) specifier; one of which should be criterion 1 (tolerance) or 2 (withdrawal);
* Primary complaints according to Mini-International Neuropsychiatric Interview (MINI) should be alcohol problems;
* Participants must have gone through a detoxification program, have a clearly stated desire to stay abstinent and present at baseline with the following: be alcohol abstinent for at least 3 days, benzodiazepine free for at least 3 days, and a Clinical Institute Withdrawal Assessment (CIWA) score \<10;
* Age 18-65 years at screening;
* Males, or females who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or who are non-pregnant, non-lactating and using a medically accepted method of contraception; these include condoms with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), and hormonal contraceptives;
* Body Mass Index (BMI) \>16 kg/m\^2;
* Breath alcohol concentration \< 0.02% (at screening and baseline)

Exclusion Criteria:

* Participants requiring pharmacological treatment for a primary diagnosis of major depressive disorder, anxiety, panic disorder or social phobia;
* Participants with psychotic disorders (according to MINI);
* Participants with a medium or high suicidality risk (as assessed by MINI)
* Active substance abuse (resulting in either physical or mental damage as defined by International Statistical Classification of Diseases and Related Health Problems, 10th revision \[ICD10\] or dependence other than alcohol (excluding nicotine) within 12 months prior to screening, e.g. cannabis, benzodiazepine, amphetamines, chlo(r)methiazole, opiates, cocaine, hallucinogens or other substances;
* Use of one of the following drugs during the last 14 days prior to screening: cannabis, amphetamines, opiates, cocaine, hallucinogens;
* Use of any medication that can have an effect on alcohol consumption within 30 days of study initiation, including naltrexone, acamprosate, disulfiram, ondansetron, topiramate, selective serotonin reuptake inhibitors (SSRIs), mirtazapine, varencicline, gabapentin, levetiracetam;
* A clinically relevant visual disturbance, such as cataract, color blindness, macular degeneration, glaucoma or retinal disease;
* Untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, cardiovascular, hematological, immunological or cerebrovascular disease, malignancy, or other chronic and/or degenerative process at screening;
* Any clinically meaningful abnormal laboratory, vital sign, physical examination or electrocardiogram (ECG) finding which, in the opinion of the investigator, may interfere with the interpretation of safety or efficacy evaluations;
* QTc interval (Fridericia corrected) at screening \>450 ms (male), \>470 ms (female);
* Serious neuropsychiatric condition that can impair judgment or cognitive function (including dementia or amnestic disorder) to an extent that providing informed consent or complying with treatment is precluded;
* History or present evidence of epileptic disorders or withdrawal seizures;
* History of substance withdrawal delirium;
* Breast-feeding woman, or a positive result of urine pregnancy test (at screening), or plan to become pregnant during the course of the trial (females only);
* Pending legal charges with the potential for incarceration, probation, or parole;
* Homelessness (less than 2 months stable residence);
* Participation in a clinical trial during the 3 months prior to screening.

Primary outcomes:
measure: Percentage of Heavy Drinking Days
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Drinks Per Drinking Day
timeFrame: 12 weeks
measure: Number of Relapses Into Heavy Drinking
timeFrame: 12 weeks
measure: Number of Lapses Into Any Drinking
timeFrame: 12 weeks
measure: Time to First Relapse Into Drinking
timeFrame: 12 weeks
measure: Percentage of Abstinent Days
timeFrame: 12 weeks
measure: Percentage of Participants With Complete Abstinence
timeFrame: 12 weeks
measure: Global Functioning: Clinical Global Impression (CGI) - Severity of Illness
timeFrame: Day 84
measure: Global Functioning: CGI - Therapeutic Effect
timeFrame: Day 84
measure: Change From Baseline in Craving Visual Analog Scale (VAS) Score
timeFrame: Baseline and Day 84
measure: Change From Baseline in Motivation VAS Score
timeFrame: Baseline and Day 84
measure: Change From Baseline in Mood VAS Score
timeFrame: Baseline and Day 84
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to 16 weeks
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: de Bejczy A, Nations KR, Szegedi A, Schoemaker J, Ruwe F, Soderpalm B. Efficacy and safety of the glycine transporter-1 inhibitor org 25935 for the prevention of relapse in alcohol-dependent patients: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2014 Sep;38(9):2427-35. doi: 10.1111/acer.12501.