Human Laboratory Study of ANS-6637 for Alcohol Use Disorder
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 43
- 试验地点
- 3
- 主要终点
- Craving - "How Strong is Your Craving to Drink Alcohol" Visual Analog Scale (VAS) Item
研究概览
简要总结
Primary: The primary objective of this study was to evaluate the effects of 2 different doses of ANS-6637, 200 mg (given as 2 x 100 mg tablets) and 600 mg (given as 2 x 300 mg tablets) once a day, and matched placebo, on alcohol cue-elicited alcohol craving during a human laboratory paradigm after 1 week of daily dosing among subjects with moderate to severe alcohol use disorder (AUD) as confirmed by the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5™).
Secondary: Secondary objectives included evaluation of ANS-6637 200 mg, ANS-6637 600 mg, and matched placebo on reduction of alcohol consumption, alcohol craving, cigarette smoking (among smokers) and nicotine use (among nicotine users), mood, sleep, alcohol use negative consequences, study retention, and safety and tolerability throughout the last 4 weeks of the treatment phase of the study.
详细描述
Methodology: This study was a 3-arm, double-blind, randomized, placebo-controlled, parallel group, 3-site study designed to assess the effects of ANS-6637 as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting. After signing informed consent, subjects were screened for eligibility and had other baseline assessments. Screening was permitted over a 14-day period and most baseline assessments were performed on the day of randomization. If eligible for the study, 81 subjects were to be randomized using a stratified permuted block randomization procedure in an approximate 1:1:1 ratio (targeting 27 subjects per group and 27 subjects per each of 3 clinical sites) to receive either ANS-6637 200 mg once daily, ANS-6637 600 mg once daily, or matched placebo for 5 weeks. Clinical site was used as the stratification variable. Subjects were seen in the clinic at screening, at randomization and 5 other times during the study. A final followup telephone interview was conducted 2 weeks after the end of study in-clinic visit. After the first week of investigational product (IP) administration at Study Week 2, subjects underwent a cue reactivity session including 4 individual visual analog scale (VAS) items assessing alcohol craving and one item assessing beverage liking.
Number of Subjects (planned and analyzed): 81 planned; 43 analyzed. The study was put on clinical hold and then stopped early due to clinically significant AEs.
Investigational Product, Dosage, and Mode of Administration:
The target doses were 200 mg (2 x 100 mg tablets) and 600 mg (2 x 300 mg tablets) of ANS-6637 by oral administration once daily for 5 weeks. Subjects in the placebo group took an equivalent number of identically matched placebo tablets (2 per day) by oral administration once daily for 5 weeks.
Duration of Treatment: Each subject participated in the study for up to 10 weeks, including up to 2 weeks of screening, 5 weeks of treatment, one end-of-study visit during the week following the last treatment dose, and a final telephone contact 2 weeks after completing treatment for a safety follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Current (past 12 months) substance use disorder of at least moderate severity (4 or more criteria) for any psychoactive substance other than alcohol and nicotine, including sedatives and hypnotics, as defined by DSM-5 criteria.
- •Urine drug test positive performed during screening or baseline for any of the following substances:
- •benzodiazepines,
- •amphetamines,
- •methamphetamine,
- •buprenorphine,
- •barbiturates,
- •and/or MDMA. Note: Testing for THC was included in the urine drug test; however, subjects who tested positive for THC were still eligible to participate in the study unless they had moderate or greater severity for cannabis use disorder as indicated by DSM-5 criteria. The results for THC were recorded for information only. If positive for opioids or oxycodone but recent opiate use for acute pain was reported by the subject, then the subject could be included at the discretion of the investigator.
- •VAS craving rating ("How strong is your craving to drink alcohol") during first presentation of alcohol cue <5 during the screening cue reactivity session.
- •Have 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 AUD or a history of any seizure disorder.
- •Have participated in any behavioral and/or pharmacological intervention research study for the treatment of alcoholism where the last intervention was within 3 years prior to signing the informed consent.
- •Be mandated by the court to obtain treatment for alcohol-dependence, or has probation or parole requirements that might interfere with study participation.
- •Be anyone who in the opinion of the investigator could not be safely withdrawn from alcohol without medical detoxification.
- •Have undergone medical detoxification (e.g., reports using a benzodiazepine) during the screening phase (prior to randomization).
- •Have been treated with a pharmacotherapy for alcohol use disorder within 6 months prior to randomization.
- •Have any of the following, based on DSM-5 criteria as assessed using theMINI:
- •Current or lifetime diagnosis of psychotic disorders,
- •Current bipolar disorder,
- •Current major depressive episode,
- •Current (past 3 months) eating disorder (anorexia or bulimia), or
- •Within past year diagnosis of panic disorder with or without agoraphobia. Note: Subjects diagnosed with psychiatric disorders not specifically excluded above could be included at the discretion of the PI as long as the concurrent treatment for the comorbid psychiatric condition does not compromise the study integrity by virtue of its type, duration, or intensity.
- •Have any of the following:
- •attempted suicide past year,
- •current (past year) suicide behavior disorder in accordance with DSM-5 criteria as assessed using the MINI (see note below about assessment of subjects diagnosed at low risk),
- •current (since screening MINI) suicidality risk as indicated during the conduct of the C-SSRS with concurrence after a study physician's evaluation if the response to C-SSRS questions 1 or 2 is "yes"). Note: The MINI suicidality module rates scores of 1 to 8 as a diagnosis of low risk of suicidality. As the MINI questions that could result in a low risk score are considered inadequate to fully determine the potential suicidal risk of an individual (e.g., "Feel hopeless" and "Think that you would be better off dead or wish you were dead?" responses of "yes" dictates a score of 1 for each question), any subject who scores in the low risk category should be evaluated further by a study physician who should document whether the subject is appropriate for study inclusion based on his/her clinical judgment of the potential suicide risk of the subject. Likewise, if the subject responded "yes" to either the first 2 questions on the screening C-SSRS performed on the day of randomization as a final eligibility check, the subject should also have been evaluated by a study physician for current suicidality risk, who should document the subject's suitability for study inclusion.
- •Have moderate or serious dementia as assessed by clinical exam.
- •Be pregnant or breast-feeding or have plans to become pregnant at any time during the study or within 7 days after the last dose of IP.
- •Have clinically significant abnormal laboratory values, including elevation of liver enzymes (AST or ALT > 2.5 x upper limit of normal or total bilirubin > 1.5 x the upper limit of normal).
- •Have abnormal calculated creatinine clearance defined as < 80 mL/minute for subjects ≤ 55 years of age and < 65 mL/minute for subjects > 55 years of age.
- •Have a serious or unstable medical illness or any potentially life-threatening or progressive medical condition other than addiction that may compromise subject safety or study conduct.
- •Be currently undergoing psychotherapy by a licensed therapist or psychiatrist for alcohol problems. NOTE: Current psychotherapy was to be considered on a case-by-case basis. Psychotherapy for a disorder that could be related to the subject's use of alcohol should be exclusionary. However, shorter term focused behavioral therapy for defined problems for non-alcohol related problems could be acceptable.
- •Have data suggesting cirrhosis of the liver (albumin < 3.2 g/dL, or ascites by physical exam).
- •Have been previously treated with ANS-6637 for any reason.
- •Have had gastric bypass surgery.
- •Have had a severe reaction to disulfiram while drinking alcohol requiring medical attention.
- •Have a history of atherosclerotic cardiovascular disease including angina pectoris, myocardial infarction, stroke, transient ischemic attack, peripheral vascular disease or revascularization procedures or clinically significant ECG indicative of cardiovascular disease. Note: medically controlled hypertension is not exclusionary.
- •History of syncope, palpitations, or unexplained dizziness at screening.
- •Had a prior history of any severe adverse reactions to ethanol [e.g., flushing (noticeable redness of the neck or throat) and/or increased heart rate (subject reports sensation of increased heart rate or palpitations) after drinking alcohol].
- •Report heavy drinking of alcohol within 2 days on TLFB prior to screening and have a negative result on EtG urine test.
- •Have Parkinson's Disease or a family history of Parkinson's Disease.
- •Have restless legs syndrome and receiving dopamine agonist treatment.
- •Have attention-deficit disorder and receiving dopamine stimulant treatment.
- •Are taking a prohibited medication.
研究组 & 干预措施
ANS-6637 - 200mg
200 mg ANS-6637 (given as 2 x 100 mg tablet) once a day
干预措施: ANS-6637 (Drug)
ANS-6637 - 600mg
600 mg ANS-6637 (given as 2 x 300 mg tablet) once a day
干预措施: ANS-6637 (Drug)
Matched Placebo
2 placebo tablets once a day
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Craving - "How Strong is Your Craving to Drink Alcohol" Visual Analog Scale (VAS) Item
时间窗: Week 2
The primary efficacy endpoint is the change in the "strength" of alcohol craving Visual Analog Scale (VAS) score for the question, "How strong is your craving to drink alcohol," in response to an alcohol cue at Week 2 - after one week of investigational product treatment. The VAS has a minimum=0 and maximum=20 with higher values indicative of greater craving for alcohol (a worse outcome).
次要结局
- Number of Subjects With no Heavy Drinking Days(Last 4 weeks of treatment, from Week 2 to Week 5)
- Number of Subjects Abstinent From Alcohol(Last 4 weeks of treatment, from Week 2 to Week 5)
- WHO 1-level Decrease in Alcohol Consumption(Last 4 weeks of treatment, from Week 2 to Week 5)
- WHO 2-level Decrease in Alcohol Consumption(Last 4 weeks of treatment, from Week 2 to Week 5)
- Percentage of Days Abstinent(Last 4 weeks of treatment, from Week 2 to Week 5)
- Percentage of Heavy Drinking Days(Last 4 weeks of treatment, from Week 2 to Week 5)
- Percentage of Very Heavy Drinking Days(Last 4 weeks of treatment, from Week 2 to Week 5)
- Drinks Per Week(Last 4 weeks of treatment, from Week 2 to Week 5)
- Drinks Per Drinking Day(Last 4 weeks of treatment, from Week 2 to Week 5)
- Penn Alcohol Craving Scale (PACS)(Last 4 weeks of treatment, from Week 2 to Week 5)
- Pittsburgh Sleep Quality Index (PSQI)(Last 4 weeks of treatment, from Week 2 to Week 5)
- Patient-Reported Outcomes Measurement Information System (PROMIS) Alcohol Related Negative Consequences(Last 4 weeks of treatment, from Week 2 to Week 5)
- Profile of Mood States (POMS) Total Disturbance(Last 4 weeks of treatment, from Week 2 to Week 5)
- Craving - "Having a Drink Would Making Things Just Perfect" Visual Analog Scale (VAS) Item(Week 2)
- Craving - "If I Could Drink Alcohol Now, I Would Drink it" Visual Analog Scale (VAS) Item(Week 2)
- Craving - "It Would be Hard to Turn Down a Drink Right Now" Visual Analog Scale (VAS) Item(Week 2)