Clinical trial NCT03327792
Conditions: Alcohol Drinking
Sponsor: Yale University
Start date: 2018-02-07; Completion date: 2023-07-13
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this alcohol-interaction pilot study is to provide information on the effect of mavoglurant on the pharmacokinetics of alcohol and on alcohol responses, including stimulation, sedation, intoxication, body sway and physiological responses. The investigators propose to test the effects of 200 mg mavoglurant versus placebo on alcohol related responses. This is a between subjects double blind randomized design in which the investigators plan to run 40 subjects to obtain 28 completers.

Detailed description:
The purpose of this alcohol-interaction pilot study is to provide information on the effect of mavoglurant on the pharmacokinetics of alcohol and on alcohol responses, including stimulation, sedation, intoxication, body sway and physiological responses. The investigators propose to test the effects of 200 mg mavoglurant versus placebo on alcohol related responses. This is a between subjects double blind randomized design in which the investigators plan to run 40 subjects to obtain 28 completers.

Subjects will participate in two lab sessions, one prior to taking medication and one following 7-10 days of mavoglurant/placebo. During each session, participants will receive successive doses of alcohol over a 90 min period designed to raise their blood alcohol levels to 80 mg/dl; this dose was chosen because this is close to the legal limit of intoxication and to the peak BAC the investigators have observed in prior research studies. Subjects will be monitored throughout the lab session and will receive a phone call two days following the 2nd lab session and a follow-up appointment one week after the 2nd lab session to assess any remaining side effects from the medication.

Arms: arm 1: 200 mg mavoglurant once daily for 7-10 days arm 2: Placebo once daily for 7-10 days
Interventions: intervention 1: Mavoglurant intervention 2: Placebo
Intervention descriptions: intervention 1: 200 mg Mavoglurant intervention 2: Placebo

Protocol documents:
Prot_SAP_001.pdf: 
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CLINICAL STUDY PROTOCOL
Interventional Drug or Biologic
A Pilot Study on the Safety and Efficacy of 
Mavoglurant in Alcohol Drinking
 Protocol Number
2000021703
Protocol Version 2.9
PRINCIPAL INVESTIGATOR:
Name: Suchitra Krishnan-Sarin, PhD
Department: Yale School of Medicine Dept of Psychiatry
Telephone Number: 203-974-7595
Email Address: Suchitra.krishnan-sarin@yale.edu
IND Number: #137044
IND Holder: Dr. John Krystal
NCT Number: 
Study Phase 1:
Confidentiality Statement:  This document is a confidential communication of the study 
sponsor (Dr John Krystal, Yale University School of Medicine). Acceptance of this document 
constitutes agreement by the recipient that no unpublished information contained herein will 
be published or disclosed without the sponsor’s prior written approval, except that this 
document may be disclosed to appropriate Institutional Review Boards under the condition 
that they are requested to keep it confidential.
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REVISION HISTORY:
Revision #
Version Date
2.0
1/11/2021
2.1
7/9/2021
2.2
12/16/2021
2.3
3/28/2022
2.4
6/6/2022
2.5
8/1/2022
2.6
9/12/2022
2.7
3/07/23
2.8
2.9
6/15/23
10/26/23
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1 Synopsis
Primary Objective
The purpose of this study is to evaluate interactions between a moderate dose of alcohol and a 
non-competitive antagonist of the metabotropic glutamate receptor subtype 5 (mGLUR5), 
mavoglurant, on pharmacokinetic, physiological or behavioral responses in healthy social 
drinkers.
Study Duration
6 years, plus 1 year for data analysis
Study Design 
This pilot study will examine interactions between alcohol and mavoglurant and explore the 
effects of mavoglurant on alcohol responses. This is a between subjects, double-blind design.  
We propose to recruit 40 male and female healthy volunteers (to achieve a completer sample 
of 28 participants) who meet criteria for social drinking (i.e., consuming 1- 6 standard alcoholic 
drinks per week and having engaged in at least one and no more than 12 binge drinking 
episodes in the past year), do not meet criteria for a DSM-V Alcohol Use Disorder, and who are 
willing to abstain from alcohol during the outpatient study medication treatment phase.  
The study will consist of five parts: 1) Eligibility: Informed consent is obtained, and eligibility is 
evaluated, 2) Lab Session 1: Eligible subjects will then be exposed to a fixed dose of alcohol 
and monitor responses; we will randomize them to study medication (mavoglurant or placebo), 
3) Outpatient Medication: Subjects will come in on a daily basis (or via zoom) for 7-10 days, 
when they will be observed when they take the study medication, and adverse events will be 
monitored, 4) Lab Session 2: Subjects will again be exposed to the same fixed alcohol dose at 
the first lab session, the following morning they will go in for a blood/urine collection 5) Follow 
Up Interviews: We will follow up with participants via phone, for two days after discharge and 
in-person, one week after discharge to assess for any potential remaining adverse events. 
Number of Study Sites
This is a single site study
Study Population
40 social drinkers who are not currently seeking treatment for their drinking behavior, and who 
are willing to abstain from drinking alcohol during the study, and who are between 21-50 years 
of age.
Number of Participants
40 social drinkers will be recruited to achieve 28 completers.
Primary Outcome Variables
To evaluate the effect of mavoglurant on blood chemistries, urine toxicology and physiological 
safety measures before and after alcohol administration.
Secondary and Exploratory Outcome Variables (if applicable)
To evaluate the interactions of alcohol and mavoglurant on blood alcohol levels and 
mavoglurant levels.
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To explore the effects of mavoglurant on alcohol responses, including stimulation, sedation, 
intoxication, and cognitive/motor performance.
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2 Abbreviations
Abbreviation 
Explanation
ADP
Alcohol Drinking Paradigm
HRU
Hospital Research Unit
CMHC
Connecticut Mental Health Center
AUD
Alcohol Use Disorder
CTNA
Center for Translational Neuroscience on 
Alcoholism
AE
adverse event
ALT 
alanine aminotransferase 
AST
aspartate aminotransferase
BAC 
blood alcohol concentration 
CLIA 
Clinical Laboratory Improvement Act 
CIWA-AR 
Clinical Institute Withdrawal Assessment for 
Alcohol-revised 
DSM-5 
Diagnostic and Statistical Manual of Mental 
Disorders – Fifth Edition 
DSMB 
Data and Safety Monitoring Board 
EKG/ECG
electrocardiogram 
EtOH 
ethanol 
FDA 
Food and Drug Administration 
GGT 
gamma-glutamyl transferase 
HIPAA 
Health Insurance Portability Accountability 
Act
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IRB 
Institutional Review Board 
NIAAA
National Institutes on Alcohol Abuse and 
Alcoholism
PI 
principal investigator 
PK
pharmacokinetic
POMS 
Profile of Moods State
SAE 
serious adverse event 
CMU
Central Medical Unit
SATU
Substance Abuse Treatment Unit
CSRU
Church Street Research Unit
BIS-11
Barrett Impulsivity Scale
BIS/BAS
The Brief- Behavioral Inhibition System/ 
Behavioral Activation System
MSDM
Multi-Stage Decision Making Task
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3 Table of Contents
1
Synopsis ...........................................................................................................................3
2
Abbreviations....................................................................................................................5
3
Table of Contents .............................................................................................................7
4
Introduction.....................................................................................................................10
4.1
Introductory Statement ............................................................................................10
5
Background.....................................................................................................................11
5.1
Rationale for Project................................................................................................11
5.1.1
Preclinical – Why examine the influence of an mGluR5 modulator on alcohol 
responses? .....................................................................................................................11
5.1.2
Clinical Experience with Mavoglurant...............................................................11
6
Purpose, Risks, and Benefits..........................................................................................13
6.1
Purpose of Study/Potential Impact ..........................................................................13
6.1.1
Potential Risks..................................................................................................13
6.1.2
Potential Benefits .............................................................................................15
7
Study Objectives.............................................................................................................16
7.1
Primary Objective ....................................................................................................16
7.2
Secondary Objectives (if applicable) .......................................................................16
7.3
Exploratory Objectives (if applicable) ......................................................................16
8
Study Design ..................................................................................................................17
8.1
General Design Description.....................................................................................17
8.1.1
Study Date Range and Duration ......................................................................17
8.1.2
Number of Study Sites .....................................................................................17
8.2
Primary Outcome Variables.....................................................................................17
8.2.1
Secondary Outcome Variables (if applicable) ..................................................17
8.2.2
Exploratory Outcome Variables (if applicable) .................................................18
8.3
Study Population .....................................................................................................18
8.3.1
Number of Participants.....................................................................................18
8.3.2
Eligibility Criteria/Vulnerable Populations.........................................................18
9
Methods..........................................................................................................................20
9.1
Treatment ................................................................................................................20
9.1.1
Identity of Investigational Product ....................................................................20
9.1.2
Dosage, Administration, Schedule ...................................................................20
9.1.3
Method of Assignment/Randomization.............................................................20
9.1.4
Blinding and Procedures for Unblinding...........................................................20
9.1.5
Packaging/Labelling .........................................................................................20
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9.1.6
Storage Conditions...........................................................................................21
9.1.7
Concomitant therapy ........................................................................................21
9.1.8
Restrictions.......................................................................................................21
9.2
Assessments ...........................................................................................................21
9.2.1
Adverse Events Definition and Reporting.........................................................23
9.2.2
Pharmacokinetics (if applicable).......................................................................26
9.2.3
Biomarkers (if applicable).................................................................................26
9.3
Study Procedures....................................................................................................26
9.3.1
Study Schedule ................................................................................................29
9.3.2
Informed Consent.............................................................................................29
9.3.3
Screening .........................................................................................................29
9.3.4
Enrollment ........................................................................................................29
9.3.5
On Study Visits.................................................................................................30
9.3.6
End of Study and Follow-up .............................................................................30
9.3.7
Removal of subjects.........................................................................................30
9.4
Statistical Method ....................................................................................................30
9.4.1
Statistical Design..............................................................................................30
9.4.2
Sample Size Considerations ............................................................................31
9.5
Planned Analyses....................................................................................................31
9.5.1
Primary Objective Analysis...............................................................................31
9.5.2
Secondary Objectives Analyses.......................................................................31
9.5.3
Exploratory Objectives Analyses (if applicable) ...............................................31
9.5.4
Safety ...............................................................................................................31
9.5.5
Analysis of Subject Characteristics ..................................................................31
9.5.6
Interim Analysis (if applicable)..........................................................................31
9.5.7
Health economic evaluation .............................................................................31
9.5.8
Other ................................................................................................................31
9.5.9
Subsets and Covariates ...................................................................................31
9.5.10
Handling of Missing Data .................................................................................32
10
Trial Administration .....................................................................................................33
10.1
Ethical Considerations: Informed Consent/Assent and HIPAA Authorization .........33
10.2
Institutional Review Board (IRB) Review.................................................................33
10.3
Subject Confidentiality.............................................................................................33
10.4
Deviations/Unanticipated Problems.........................................................................34
10.5
Data Collection ........................................................................................................34
10.6
Data Quality Assurance...........................................................................................35
10.7
Study Records.........................................................................................................35
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10.8
Access to Source Documents .................................................................................35
10.9
Data or Specimen Storage/Security ........................................................................35
10.10
Retention of Records ...........................................................................................35
10.11
Study Monitoring..................................................................................................35
10.12
Data Safety Monitoring Plan ................................................................................36
10.13
Study Modification................................................................................................36
10.14
Study Discontinuation ..........................................................................................36
10.15
Study Completion.................................................................................................36
10.16
Conflict of Interest Policy .....................................................................................37
10.17
Funding Source....................................................................................................37
10.18
Publication Plan ...................................................................................................37
11
Appendices .................................................................................................................38
12
References..................................................................................................................44
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4 Introduction
4.1
Introductory Statement
This document is a protocol for a human research study. The purpose of this protocol is to 
ensure that this study is to be conducted according to ICH GCP guidelines, and according to 
CFR 21 Part 312, other applicable government regulations and Institutional research policies 
and procedures.
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5 Background
5.1
Rationale for Project
Alcohol Use Disorders (AUD’s) are leading causes of disability in the United States. At 
present, three medications are approved by the FDA for the treatment of alcohol 
dependence: disulfiram, naltrexone, and acamprosate. However, the efficacy of these 
agents is minimal to modest, and they are under-utilized in clinical community settings 
(Garbutt et al 1999, Krishnan-Sarin et al 2008).
There is a pressing need for novel medications that are more effective in reducing alcohol 
use. Development of new pharmaco-therapeutic approaches to treating AUDs should 
emerge from our understanding of the behavioral and neurochemical mechanisms mediating 
pathological alcohol drinking.  The goal of our center (the Center for Translational 
Neuroscience on Alcoholism; CTNA) is to evaluate the mechanisms through which 
disturbances in glutamate neurotransmission within cortico-limbic circuitry contribute to 
vulnerability for persistent heavy drinking, and to use this information to develop new 
therapies for alcoholism.  In previous iterations of our center we have focused on evaluating 
if modulation of fast synaptic transmission via altering the ionotropic NMDA receptor function 
alters drinking behavior; our results suggest that the NMDA receptor antagonist memantine 
reduced craving for alcohol but did not influence drinking.  In the current study, we would like 
to extend this work to examine the influence of metabotropic glutamate receptors which 
produce slower modulation of the glutamate system through second messenger systems. 
5.1.1
Preclinical – Why examine the influence of an mGluR5 modulator on alcohol 
responses?
Our focus is mGluR5 receptors which have been shown to reduce intravenous drug self-
administration and reinstatement of drug-seeking in pre-clinical studies (Duncan and 
Lawrence 2012; Kenny and Markou 2004). mGluR5s are highly concentrated in nuclei 
associated with reward pathways such as the forebrain and limbic structures, dorsal 
striatum, Nacc, lateral septum, hippocampus, and cerebral cortex (Shigemoto et al., 1993, 
Romano et al., 1995).  These receptors have also been shown to be involved in regulating 
motivation to self-administer alcohol (Hodge et al., 2006; Cowen et al., 2005; Besheer et al., 
2008) as well as binge alcohol consumption (Tanchuck et al., 2011). mGluR5-deficient mice 
voluntarily consume less ethanol, are more sensitive to the hypnotic effects of ethanol (Bird 
et al., 2008, Downing et al., 2010), and display conditioned place preference to low doses of 
ethanol (1 g/kg) which suggests that they might have increased sensitivity to ethanol’s 
centrally mediated rewarding affects.  Moreover, in alcohol-preferring rats, administration of 
the mGluR5 antagonist MPEP Into the Nucleus accumbens reduces ethanol self-
administration; an effect which is not observed when MPEP is infused into the dorsomedial 
caudate or medial prefrontal cortex (Besheer et al., 2010).  Moreover, human genetic studies 
have suggested that individuals with genetic variations in mGluR5, and the NMDA NR2A 
receptor subunits, have higher risk of developing alcohol dependence (Schumann et al., 
2008).  All the above evidence suggests there might be a role of mGluR5 receptors in 
alcohol reward/consumption.
5.1.2
Clinical Experience with Mavoglurant
Mavoglurant (AFQ056) is an experimental drug, developed by Novartis, which is a non-
competitive antagonist of the metabotropic glutamate receptor subtype 5 (mGLUR5). 
Mavoglurant was developed to treat the behavioral and cognitive symptoms of fragile X 
syndrome (FXS). Pre-clinical data looked promising (Levenga et al., 2011), but clinical trials 
with FXS have found mixed results (Gomez-Mancilla et al., 2014; Petrov et al., 2014; Scharf 
et al., 2014). Mavoglurant has also been studied in pre-clinical (Morin et al., 2010; Grégoire 
et al., 2011) and clinical trials (Berg et al., 2011; Stocchi et al, 2013) for L-DOPA-induced 
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dyskinesia (LID) in patients treated for Parkinson’s Disease. Although results looked 
promising with antidyskinetic effects of LID, there was also inconclusive data (Kumar et al., 
2013). Mavoglurant has also been studied in reducing chorea in Huntington Disease 
(Reilmann et al., 2015), and although the drug was well tolerated, the results did not suggest 
efficacy. Safety and tolerability of mavoglurant was established in a single dose trial in 
healthy male volunteers (Walles et al., 2013) and a clinical trial in patients with obsessive 
compulsive disorder (Rutrick et al., 2017), although the latter did not show efficacy. Although 
a clinical study was initiated in 2007 to assess mavoglurant on cigarette smoking, the results 
have not been published. To date, no trials have been conducted on the use of mavoglurant 
for alcohol use disorder (AUD).
Mavoglurant or AFQ056 is a structurally novel, subtype-selective, non-competitive 
antagonist at the metabotropic glutamate receptor 5 (mGluR5). We propose to use a dose of 
200 mg because according to a receptor occupancy study conducted by Novartis this dose 
occupies about 90% of the mGluR5 receptors.  The MTD of an immediate-release 
formulation of AFQ056 was observed to be 400 mg after single dose administration and 150 
mg b.i.d. after multiple dose administration in healthy subjects. We will use a modified 
release formulation which has been shown to produce less fluctuation in C-max (80-90%) 
compared to an immediate release formulation.
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6 Purpose, Risks, and Benefits
6.1
Purpose of Study/Potential Impact
The purpose of this study is to evaluate the safety and tolerability of a moderate dose of 
alcohol in combination with a non-competitive antagonist of the metabotropic glutamate 
receptor subtype 5 (mGLUR5), mavoglurant, on pharmacokinetic, physiological or behavioral 
responses in healthy social drinkers.
Prior to initiating a study to examine the influence of mavoglurant on drinking behaviors in 
heavy drinkers, we propose to conduct this study to examine the safety and pharmacokinetic 
interactions of administering mavoglurant and alcohol together.  
6.1.1
Potential Risks
The major potential risks in this study are related to administration of alcohol, mavoglurant, 
and blood drawing during the physical exam and alcohol drinking period.
Risks Associated with Study Drug, Mavoglurant:
Mavoglurant of AFQ056 has been studied in a total of 2209 study subjects who have been 
enrolled in a total of 45 completed human studies, of which 29 were Phase l studies [single-
dose: n=19; multiple-dose: n=10) and 16 were Phase II studies (eight studies in Parkinson’s 
(PD-LID) patients, five studies in Fragile X (FXS) patients, one study in HD patients, one 
study in patients with GERD and one study in patients with OCD]. In these studies, a total of 
1863 study subjects were exposed to AFQ056 while the remaining subjects received either 
placebo or an active comparator. The list of studies is included in Table 5.1 on page 47 of 
the investigator’s brochure. 
The maximum tolerated dose (MTD) of AFQ056 is 400 mg after single dose administration 
and 150 mg bid. after multiple dose administration (determined with immediate release-
clinical service form (IR-CSF) in healthy subjects).   Dose-limiting aEs were mainly 
hallucinations and other psychosis-like symptoms (e.g. paranoid reaction, anxiety, agitation, 
confusion, chaotic thoughts, disorientation in time/place, and mood changes).
Overall, the aEs observed in the various human studies were of mild to moderate severity. In 
patients with Parkinson’s disease, dizziness (11.1%) and visual hallucination (11.1%) were 
the most common aEs in the AFQ056 treatment group (Table 5-10). Dyskinesia (12.0%), 
akinesia (8.0%), fall (8.0%) and asthenia (8.0%) were the most common aEs in the placebo 
group. Other AE’s were headache (8.3%), anxiety, back pain, confusional state, 
constipation, fall, decreased hemoglobin, insomnia, muscle spasms, nasopharyngitis 
(common cold), nausea, edema peripheral (swelling in legs), orthostatic hypotension, 
parkinsonian gait, vision blurred, and asthenia, all at 5.6%. 
In Fragile X Syndrome (FXS) patients, dizziness, insomnia, and headache were the most 
frequently reported aEs on AFQ056. Dizziness was also the most commonly reported AE in 
Parkinson’s Disease-L-dopa induced dyskinesia (PD-LID), however primarily with the IR 
formulation. Other frequent aEs in PD-LID patients were mostly reflecting psychiatric 
disorders such as hallucination and illusion. In particular, the dose of 200 mg b.i.d. MR 
formulation appeared not to be well-tolerated, but this was primarily observed in patients 
receiving concomitant amantadine and there were no new safety concerns identified. 
Therefore, some flexibility in dosing is warranted to allow reduction to 150 mg b.i.d. dose, 
which had an acceptable tolerability profile.
The safety of AFQ056 in patients with moderate to severe OCD was assessed in a 
randomized, double-blind, placebo-controlled, single dose, in patients resistant to SSRI 
therapy (CAFQ056A2225; N=50). Patients in this study received AFQ056 200 mg BID up- 
and down-titration regimen (4 weeks AFQ056 BID up-titration period of 50 mg, 100 mg, 150 
mg and 200 mg, followed by 12 weeks AFQ056 200 mg fixed dose and then a 3-week down 
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titration.  This study was completed in 2015 and the results indicate that this dose of 
AFQ056 was safe and well tolerated.  There were six SAEs in three patients during the 
study. Two SAEs (otitis media and 7th nerve paralysis) in one patient from AFQ056 group 
and four SAEs in two patients from placebo group. There were three aEs (worsening OCD, 
insomnia, and moderate anxiety) which led to discontinuation of the study drug. All the 
events were considered as unsuspected to the study drug by the investigators. 
12-Oct- 2014, investigator notifications have been issued for 22 subjects in completed and 
ongoing studies, of whom 14 were PD-LID patients, seven were FXS patients, and one was 
a subject in a healthy volunteer study (Section 5.2.1.2 of Investigational Brochure). Overall 
the events listed suggest that the central nervous system (CNS) and psychiatric system 
organ class (SOCs) may be preferentially affected.
There were four cases in which a fatal outcome was reported in AFQ056 studies in patients 
with Parkinson’s disease. The only death suspected to be related to AFQ056 by the 
investigator was a case of sudden death in a 77 year old male patient with a 22-yr history of 
PD; 18 days after starting a 50 mg b.i.d. dose, the patient complained for dizziness in the 
morning and died later that day; a review of the medical information did not reveal any 
significant changes in laboratory parameters or vital signs; the patient had an anterior 
hemiblock at baseline and an old inferior and/or septal myocardial infarction could not be 
rule out. In a second case, a 67 year old female patient with PD experienced a series of 
events (status epilepticus, cardiac arrest, and hypoxic ischemic encephalopathy) preceding 
death due to a fatal respiratory arrest; the investigator suspected a causal relationship 
between the seizures, cardiac arrest, the study medication and the concomitant medications 
(trimethoprim/sulfamethoxazole and citalopram), but did not suspect a relationship between 
the fatal respiratory arrest and the study medication (see Section 5.2.1.1 of Investigational 
Brochure).
Following the first case with a fatal outcome (sudden death, see above), an internal Data 
Monitoring Committee (DMC) was established. Shortly thereafter, this was replaced with an 
external DMC, responsible for regular monitoring of safety data for AFQ056 studies at a 
project level, i.e. in all indications. In addition to the regular safety monitoring, the DMC 
performs “real time” monitoring of suspected unexpected serious adverse reaction 
(SUSARs), deaths/outcomes leading to death, and serious cardiac and psychiatric events 
(SOC) for all ongoing studies.
Risks associated with alcohol:
Many medical conditions could potentially be worsened by acute alcohol administration (e.g., 
liver disease, cardiac abnormality, pancreatitis, diabetes, neurological problems, and 
gastrointestinal disorders). As a result, subjects with medical problems as revealed by 
physical exam and laboratory findings will be excluded from the study.
Alcohol may also cause nausea in high doses; however, nausea is not expected at the dose 
being used in this sample of healthy volunteers who will report prior experience of 
consuming alcohol levels similar to the quantity used in this study. Alcohol dosing will be 
calculated using published gender specific algorithms based on estimated body water 
determined from height, weight, and age and the amount of alcohol provided will raise their 
blood alcohol levels to 80 mg/dl which is the legal limit of intoxication to levels.
Another area of potential risk to subjects under the influence of alcohol involves their safety 
during the experimental procedures. Although impairment of gross motor coordination in 
these subjects may occur, all subjects will be under the supervision of the experimenters to 
prevent possible accidents such as falls. To ensure the safety of our subjects, they will be 
monitored until their BAC falls to below .02 or until 6pm. All participants will be provided with 
transportation to and from the lab sessions to ensure their saftey. 
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There is no data looking at the effects of alcohol with mavoglurant. However, this interaction 
is the purpose of this study and the amount of alcohol that will be given subjects is no more 
than the amount they may drink in a social environment.
Risks associated with urine collections:
Screening urine collections are performed primarily as safeguards to subjects and should 
add no risks other than those normally associated with these procedures. Subjects will have 
approximately 50cc of blood drawn at the PE appointment to determine liver and
kidney functioning. We will draw approximately 70.5cc of blood during the first lab session 
and 85.5cc of blood at the second lab session for BALs and health profile and PK samples. 
The morning after lab session 2, 50cc’s of blood is drawn. At the 1 week follow up 50cc will 
be drawn again for health profile. Therefore, the total amount of blood drawn during the 
study (306 ml) is well within the HIC guidelines of 450 cc within 8 research weeks, and the 
blood loss poses minimal risk in healthy subjects. We will advise subjects against donating 
blood for 6 weeks following study participation.
Risks associated with rating scales and questionnaires:
These are all noninvasive and should add no risk. The major disadvantages are the time 
taken to complete them or possible discomfort in answering certain items. 
Risks Associated with Blood Drawing:
Drawing blood is a safe and standard medical procedure. Sometimes a bruise will occur at 
the puncture site and rarely a blood clot or infection will occur in the vein. Certain individuals 
may feel light-headed during venipuncture. 
Risks Associated with Electrocardiograms (EKG/ECGs) at the physical exam:
There is no pain or discomfort during an EKG/ECG; however, removing the pads may cause 
some irritation to the skin.
Risks Associated with Intravenous Access:
Insertion of an intravenous catheter involves risk for hematoma at the site of the venous 
puncture. Very rarely, venous puncture can also result in a blood clot or infection.
6.1.2
Potential Benefits
Subjects will not benefit from participating in this study. Subjects may benefit by receiving, at 
no charge, a thorough screening and diagnostic evaluation, the results of which may be 
shared with them, and if they wish, with their physicians. This research will also benefit 
scientific knowledge and may lead to the development of a potential therapy for alcoholism.
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7 Study Objectives
7.1
Primary Objective
The primary objective of this study is to evaluate the safety and tolerability of mavoglurant 
when used in combination with a moderate dose of alcohol in healthy social drinkers.
Specific Aim 1: To evaluate the effect of mavoglurant on blood chemistries, urine toxicology 
and physiological safety measures before and after alcohol administration.
7.2
Secondary Objectives (if applicable)
Specific Aim 2: To evaluate the interactions of alcohol and mavoglurant on blood alcohol 
levels and mavoglurant levels.
We collected and analyzed mavoglurant levels from the first 10 participants who completed 
this study.  These results did not show any changes in mavoglurant levels after alcohol 
administration. We collected blood sample from the additional 14 participants who recently 
completed the study but at present we do not have the funding to complete these assays 
which are rather expensive and can only be conducted by one company in India. So we 
would like to not conduct these assays on the new samples but we would like to retain the 
deidentified samples and conduct the assays at a later date if and when funding becomes 
available
7.3
Exploratory Objectives (if applicable)
Exploratory Aim: To explore the effects of mavoglurant on alcohol responses, including 
stimulation, sedation, intoxication, and cognitive/motor performance.
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8 Study Design
8.1
General Design Description
Double blind placebo-controlled trial of mavoglurant vs. placebo in light social drinkers (i.e., 
consuming 1- 6 standard alcoholic drinks per week and having engaged in at least one and 
no more than 12 binge drinking episodes in the past year). Participants will not meet criteria 
for a DSM-V Alcohol Use Disorder and must be willing to abstain from alcohol during the 
outpatient medication treatment phase.  We propose to recruit 40 male and female social 
drinkers (to achieve a completer sample of 28 participants).  
Subjects will sign informed consent and eligibility will be determined.  Eligible subjects will 
participate in two alcohol administration lab sessions.  They will be randomized to receive 
either 200 mg/day of mavoglurant or placebo for 7-10 days (14 in each study arm).  During 
the outpatient medication administration phase, subjects will be observed daily as their 
medication is administered. Adverse events will be assessed.  The first lab session will occur 
on Day 0 (prior to start of study medication) and the second lab session will occur following 
7-10 days (as scheduling permits) of study medication.  During each lab session, subjects 
will receive six successive doses of alcohol over a 90-min period designed to raise their 
blood alcohol levels to 80 mg/dl. Outcomes will include adverse events (during outpatient 
period and the lab session), safety labs (before and after drug and after alcohol), PK/PD of 
drug and alcohol, behavioral tests of cognition and body sway as well as self-reports of 
intoxication and other alcohol effects.  Study staff will check in with subjects on the two days 
following the second lab session and an in-person follow up appointment will be scheduled 1 
week after the second lab session.
8.1.1
Study Date Range and Duration
Subjects will participate in a screening visit and will complete  lab session 1.  Subjects will be 
seen daily, via video chat, to take their medication dose for the next 6 days (or up to 9 days, 
for scheduling reasons). On Day 7 (or up to day 10), they will come in for lab session 2 and 
take their final dose of medication. Subjects will then be followed up 1 week after the final 
lab session.  
The enrollment period to accrue the 28 completing subjects is expected to be 6 years.
8.1.2
Number of Study Sites
One study site.  Yale University will be the only site for this study
8.2
Primary Outcome Variables
The primary outcomes are clinical and laboratory measures including complete blood count 
and serum chemistries with calcium, magnesium, phosphate, liver function tests, B12 and 
TSH blood chemistries.   We will also assess adverse events, heart rate, and blood pressure 
during the outpatient treatment period and during alcohol administration.  
8.2.1
Secondary Outcome Variables (if applicable)
The secondary outcomes are blood alcohol levels on mavoglurant compared to no drug, and 
drug levels of mavoglurant before and after alcohol administration.   
8.2.2
Exploratory Outcome Variables (if applicable)
Alcohol effects on stimulation, sedation, intoxication (Biphasic Alcohol Effects Scale), 
cognitive motor performance and physiological responses (blood pressure and heart rate) 
measured during the mavoglurant session and compared to responses measures during the 
baseline no-drug session.  
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8.3
Study Population
Participants will be social drinkers (consuming 1- 6 standard alcoholic drinks per week and 
having engaged in at least one and no more than 12 binge drinking episodes in the past 
year) who are not currently seeking treatment for their drinking behavior, and who are willing 
to abstain from drinking alcohol during the study, and who are between 21-50 years of age.
8.3.1
Number of Participants
We propose to recruit 40 male and female social drinkers (to achieve a completer sample of 
28 participants).  We anticipate having to consent approximately 90 subjects to reach these 
enrollment numbers.
8.3.2
Eligibility Criteria/Vulnerable Populations
All potential participants will be screened over the phone and if they appear to be eligible, 
will be brought in to be consented by a member of the research staff.  A physical exam will 
be scheduled and reviewed by our Study Physician, and a psychological evaluation will be 
conducted by a trained clinical psychologist, or licensed social worker, to determine 
eligibility. In addition the participant’s medical history may be verified from medical records 
by the study physician and study psychologist.
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
1) Screened light social drinkers who are aged 21-50.  
2) Able to read English at 6th grade level or higher and to complete study evaluations, 
3) Consume 1- 6 standard alcoholic drinks per week, and has engaged in at least one 
and no more than 12 binge drinking episodes in the past year, 
4) Willing to abstain from drinking alcohol during the outpatient study medication 
treatment period.
5) Fully vaccinated against COVID-19 (as defined by CDC guidelines)
An individual who meets any of the following criteria will be excluded from participation in 
this study:
1) Seeking treatment for alcohol drinking.
2) Current DSM-V abuse or dependence criteria for alcohol, dependence criteria for  
other substances, other than nicotine.  
3)  Positive test results at any appointments after the initial intake appointment on urine 
drug screens conducted for opiates, cocaine, marijuana, benzodiazepines and/or 
barbiturates.  
4) Regular use of psychoactive drugs including anxiolytics and antidepressants.  
5) Psychotic or otherwise severely psychiatrically disabled.  
6) Any medical conditions (including hepatic and renal impairment) that would 
contraindicate the consumption of alcohol or administration of mavoglurant.
7) History of neurological trauma or disease, delirium, or hallucinations, or any 
significant systemic illness or unstable medical condition. 
8) Women who are pregnant, nursing, or refuse to use a reliable method of birth control. 
Urine pregnancy tests will be completed at intake and prior to administration of 
alcohol. 
9) Subjects who report disliking spirits will be excluded because hard liquor will be 
provided during the alcohol administration. 
10)  Subjects who have taken any investigational drug and/or participated in another 
study which involves additive blood sampling and/or interventional measures that 
would be considered excessive in combination with the current protocol within 4 
weeks immediately preceding admission to the treatment period.  
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11)
Subjects who report any daily drug use during the 30 days prior to randomization for 
the following: anxiolytics, beta blockers, central nervous system stimulants, 
hypnotics, non-therapeutic doses of neuroleptics and antidepressants, drugs with 
psychotropic activity or drugs which cause excessive sedation. 
12) Subjects who have donated blood within the past six weeks. 
13)  Current use (within 30 days of screening) of specific psychoactive medications (e.g., 
typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic 
corticosteroids, or medications with significant central anticholinergic activity, etc.)
14) Current use of warfarin. 
15) Use of any medications that are contraindicated with mavoglurant and alcohol. 
16) AST, ALT, total bilirubin >1.5 times upper normal; serum creatinine, >2 times upper 
normal limit, total bilirubin>1.5 times ULN; Serum creatinine >2.0 times ULN. 
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9 Methods
9.1
Treatment 
9.1.1
Identity of Investigational Product
The study drug being used in this study is AFQ056 (Mavoglurant). Mavoglurant has not been 
approved for clinical use by the FDA. Mavoglurant oral tablets and matching placebo will be 
provided by Novartis.
9.1.2
Dosage, Administration, Schedule 
Subjects will take 200mg of Mavoglurant each day (2 x 100mg modified release tabs or 
matching placebo) for 7-10 days.  Study drug will be prepared and packaged by the 
Investigational Drug Services (IDS) at Yale-New Haven Hospital (YNHH).  Any dose pausing 
or dose discontinuation will be decided by the PI and Study Physician.
9.1.3
Method of Assignment/Randomization 
This is a double-blind, placebo-controlled study.  The alcohol center biostatisticians (Dr. 
Gueorguieva and Pittman) will create a randomization code list and forward it to the YNHH 
IDS pharmacy who will prepare the medication supply for each participant.  
9.1.4
Blinding and Procedures for Unblinding 
All staff and subjects will remain blind throughout the study.  Only YNHH IDS and the study 
biostatisticians will have access to the blinding information.  The PI will make the 
determination of if/when the blind needs to be broken.
9.1.5
Packaging/Labelling
Bulk supplies of the drug and placebo will be shipped from the company to the YNHH IDS in 
the form for 100 mg modified release tablets.  The dose to be administered will be 200mg 
(two 100mg tablets) during the 7-10 day medication administration period.  YNHH IDS will be 
responsible for monitoring drug supply and expiration.
Yale IDS will label all drug dispensed for this study.
9.1.6
Storage Conditions
Study drug will be received and stored under proper light/temperature conditions at YNHH 
IDS.  Research staff will pick up the drug and dispense as appropriate to each subject.  
Expiration dates are observed, and drug will be dispensed accordingly.  If drug needs to be 
returned, study staff will return to IDS and document appropriately.  If called for by the study 
sponsor, the PI, and Novartis, IDS will destroy remaining study drug and provide 
documentation.
9.1.7
Concomitant therapy
Concomitant medications for each subject will be reviewed by the study physician prior to 
starting study medication.  Warfarin use is not allowed.  For all subjects, medications and 
illicit drugs that are forbidden during the study include opiates, cocaine, benzodiazepines 
and barbiturates. Regular use of psychoactive drugs, except for individuals on a stable dose 
of an antidepressant for at least 2 months. Also, any subjects who have taken any 
investigational drug within 4 weeks of the anticipated date of the first study dose. 
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9.1.8
Restrictions
Use of any illicit drugs is forbidden during study participation.  Subjects are also asked not to 
come into the clinic for study appointments with a positive blood alcohol level (BAL).  Since 
alcohol drinking is harmful to an unborn child, pregnant women may not participate in this 
study. As a result, the following precautions are necessary for female participants: 1) 
Repeated pregnancy test will be performed using a urine sample. A positive pregnancy test 
will result in them being excluded from the study, 2) females of childbearing potential must 
agree to use a reliable method of birth control during the study.  Nursing mothers will also be 
excluded from the study.
9.2
Assessments
a) Socio-demographic/General Information: At intake, demographic data, medical history 
and family psychiatric history will be assessed with interviews and self-report forms that 
provide data on age, race, socioeconomic status, marital status, educational and 
occupational levels, and significant medical history.  These are adapted from previous 
diagnostic and clinical studies at this center. As of the restart of the continuation of this study 
May 2022 this assessment had several sections separated out into individual assessments. 
These are listed below: Time to 1st Cigarette (Fagerstrom ND), NIAAA alcohol questions on 
Alcohol Questions, SSADDA Risk/Protective Factors. 
b) SCID: The Structured Clinical Interview for DSM-V (SCID; First, et al., 1996) will be used 
to determine psychiatric diagnoses. This interview assesses DSM-V current and lifetime 
psychiatric diagnoses for anxiety, mood, psychotic, alcohol and substance use, somatoform, 
and eating disorders.
c) Time-Line Follow-Back Assessment Method: (Sobell & Sobell, 1992).  This interview 
procedure will be used to obtain quantity/frequency alcohol consumption data for each day 
during the 30-day period prior to the study, during the outpatient stabilization period, and 
during the one month follow-up 33 Subjects are given a blank calendar covering the time 
interval to be re-constructed, and are asked to reconstruct retrospectively their drinking 
behavior over that interval. The process is facilitated by establishing anchor points (e.g., 
holidays, anniversaries, major national events, etc.). It can be scored to provide the number 
of days on which various levels of consumption occurred. The time-line method has good 
test-retest reliability and good validity for verifiable events. It has been used in numerous 
studies to compare pre- to post-treatment drinking.
d) SAFTEE: (Levine & Schooler, 1986) This is a standardized form for collecting side effects 
and adverse events. The SAFTEE includes 1) open-ended questions about any changes in 
physical or health problems, appearance, or activity level, and 2) yes/no responses to a 
specific list of symptoms (which correspond to anticipated side effects associated with NRT) 
for a specified time. For each symptom reported on the SAFTEE a rater also records the 
date of onset, severity (minimal, mild, moderate, severe), whether it was drug-related, and 
action taken. The SAFTEE is administered at baseline and daily during medication 
appointments and again before and after each alcohol challenge. We will monitor the 
number of patients experiencing symptoms and the severity of symptoms.
e) Biphasic Alcohol Effects Scale (Martin et al., 1993) This 14-item self-report, unipolar 
adjective rating scale will be used to measure the stimulant and sedative effects of alcohol 
during the two lab sessions. This instrument has been found to be sensitive to naltrexone's 
effects on alcohol intoxication. 
f) Drug Effects Questionnaire -5 (Morean et al., 2013) The DEQ-5 asks the individual to 
report how they feel and five items: FEEL a drug effect, feel HIGH, DISLIKE the effects, 
LIKE the effects, and want MORE of the drug (in this case alcohol). Each item is assessed 
with a separate, unipolar 100mm visual analog scale rated from “not at all” to “extremely”. 
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g) Blood Alcohol Levels: Blood samples will be drawn to measure plasma levels of blood 
alcohol concentration (BAC) during the two lab sessions.   Blood samples will be spun at 
room temperature and the serum will be stored at -4°C.  Sample will be defrosted and 
analyzed using a clinical alcohol analyzer from Analox Instruments that uses a rapid high-
performance alcohol analysis procedure using alcohol oxidase. 
h) Health Profile and Urinalysis: Chemistry and CBC Panels will be drawn at baseline, prior 
to the lab sessions, the morning following the lab sessions, and at follow-up. Urinalysis will 
also be done at these times.  Additionally, a pregnancy test for females will be done at intake 
and prior to both lab sessions.
i) Psychophysiological Measures: will include heart rate and blood pressure. The cuff of the 
Dinamap will be on subject’s dominant arm since the IV will be placed in the non-dominant 
arm.
j) Multi-Stage Decision Making Task (MSDM): The MSDM is a reinforcement learning 
paradigm that quantifies the degree to which subjects can integrate recent trial-to-trial 
information about a stimulus’ likelihood of reward with acquired knowledge about whether 
some choices generally lead to disadvantageous outcomes vs. others that more often lead 
to reward. Each MSDM trial requires choices to be made in two stages.  In the first MSDM 
stage, one’s choice probabilistically leads to another set of choices.  Then in the second 
stage, subjects learn that only some stimuli are likely to give rewards. Participants will get 
paid based on how much “treasure” they receive on the trials. Out of the 3 trials, they will be 
paid their highest score. So if the win treasure 10 times, then 15, then 12; they will receive 
$15. Payments are expected to be $20 or less.
k) Concomitant Medications: A list of any other medications taken prior to the lab sessions, 
during the outpatient medication treatment period and through the follow-up will be kept for 
each subject indicating dosage, start date, end date, and indication. This will include all 
prescribed and over the counter medications.
l) Plasma Mavoglurant (AFQ056) levels: Blood samples will be stored at -700C and will be 
sent to Veeda Labs in India for analyses. The lab has a fully validated, FDA bioanalytical 
method available.
m) Body Sway: will be measured using the Wii balance board (software developed by 
Nelson & Lim, University of Minnesota). Objective assessments of the effects of alcohol are 
an important supplement to measures of subjective response of alcohol effects. Traditional 
methods of assessing balance have been prohibitive based on complexity or cost. However, 
a novel software package developed by researchers at the University of Minnesota allows 
for a practical assessment of balance using the Nintendo Wii Fit Balance Board. With 
supervision, participants will simply stand on the board, which is very sensitive to weight 
distribution, for 30 seconds while data on their weight distribution patterns are collected.
n) Yale Craving Scale (YCS; Rojewski et al., 2015): Labeled Magnitude Scale (gLMS), has 
been extended to measure hedonic ratings for foods, and we have adapted it for rating 
craving for tobacco and alcohol. It is not subject to the ceiling effects that often occur in 
craving research. We have been collecting craving data using this scale in our ongoing 
projects and the findings from this scale have been found to parallel those obtained using 
the Alcohol Urge questionnaire. A significant advantage of this scale is that following 
completion of baseline training to match perceived intensity of craving to the perceived 
brightness from the sun, each assessment timepoint only consists of a single visual analog 
scale of craving, making it very easy to administer.
o) Quality of Drinks Rating Scale (QDRS): This assessment first asks the participant to rate 
a variety of alcoholic beverages on an 11-point Likert scale. The next two questions are write 
in questions “What is your favorite alcohol?” and What is your favorite alcohol drinks?” For 
the next two questions the participant selects their preferred alcohol drink for the study’s 
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drinking session. The liquor is selected from a list of 5 options. Lastly the participant writes in 
their top three fruit juice mixers.
p) Alcohol Effects Scale (AES): This 6-item questionnaire has the participant rate how they 
are feeling from the alcohol. There is a 10-item Likert scale ranging from 1 (Not at all) to 10 
(extremely).
q) Menstrual Cycle Data: Self-reports will be obtained from all women on their 
menstrual/gynecological status.
r) Deary-Liewald reaction time task (Deary, et al., 2010): This computer task consists of two 
parts the Simple Response Time task (SRT) with just one stimulus, and when it appears, the 
participant needs to respond with the one response. Then there’s the Choice Response 
Time task (CRT) that has multiple stimuli, and each stimulus requires a different response.
s) Conners’ Continuous Performance Test II (CPT II; Connors, 2000): This computer task 
involves the participant pressing the space bar or clicking the mouse button when a letter 
other than X shows up onscreen.  Letters appear on the screen with different time intervals 
between each one. Exactly 14 minutes is required for completion.
t) PROMIS Global Health: provide an assessment of a participant’s individual assessment of 
his/her health (physical, emotional, and social), including an overall rating of pain
u) Digits Backwards: from the Digit Span subtest of the Wechsler Adult Intelligence Scale 
(WAIS-IV) (29): as a legacy, objective measure of working memory, a factor associated with 
poor decision making in those with AUD.
v) PROMIS Cognitive Function: will assess mental acuity, concentration, verbal and 
nonverbal memory, and verbal fluency and provide an assessment of a participant’s 
perception of changes in cognitive abilities over the prior 4 weeks.
w) Barrett Impulsivity Scale (BIS-11): is an 8-item trait measure of impulsiveness that yields 
two, 4-item subscales: (lack of) Self-Regulation (α = .75) and Impulsive Behavior (α = .72).
x) Behavioral inhibition/activation system (BIS/BAS): is a 13-item measure that will be used 
to assess behavioral activation and behavioral inhibition, in response to rewards and 
punishment. We will use the Brief BIS/BAS, which has demonstrated scalar measurement 
invariance groups of interest (e.g., sex, age, race, education level, family history status, 
binge drinking status, and cigarette smoking status), as well as good convergent, 
discriminant, and predictive validity.  
y) UPPS Impulsive Behavior Scale (urgency subscales): evaluates the tendency to engage 
in impulsive drinking in response to negative and positive affect.
z) Self-reported Habit Index (SRHI - Alcohol): provides a self-report measure (6-item) of the 
degree to which alcohol drinking is habitual based on features of automaticity, lack of control 
and identity in human subject studies.
aa) PROMIS Sleep and Impairment Measures: will measure past 7-day waking alertness, 
sleepiness, and impairment in function related to poor sleep because insomnia has been 
shown to be related to substance use and associated impairment.
ab) AUDIT-C: a 3-item well-deployed quantity/frequency measure of alcohol use.
ac) PROMIS Nicotine Dependence (ND): This 4-item scale will assess severity of nicotine 
dependence for cigarette smokers.
ad) Time to 1st Cigarette (Fagerstrom ND): As a legacy measure of nicotine dependence, we 
will retain the item assessing time to the 1st cigarette of the day from the Fagerström Test of 
Nicotine Dependence
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ae) NIAAA alcohol questions on Alcohol Questions: Longer-term drinking will be assessed 
with 6 questions recommended by the NIAAA Council’s Task Force on Recommended 
Alcohol Questions, including past 12 months patterns of alcohol use and lifetime max drinks
af) SSADDA Risk/Protective Factors: Environmental Factors experienced prior to age 13 will 
be assessed with a brief module from the SSADDA that was developed by Drs. Gelernter 
and Kranzler in 2002 to assess major environmental risk and protective factors associated 
with AUD, based on data presented at a NIAAA sponsored gene x environment workshop 
meeting.
9.2.1
Adverse Events Definition and Reporting
Adverse Events (AE) will be assessed from the time a subject starts the study through the 
final follow up appointment.  The SAFTEE (see description above in section 6.2) will be used 
to assess any AE’s at each visit.  This procedure involves asking subject open-ended 
questions (e.g. How have you been feeling since your last visit) as well as reviewing a 
specific list of side-effects associated with the study medication and having the subject 
respond yes/no.
Definitions
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 (a)).
An AE or suspected adverse reaction is considered “serious” (SAE) if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes: 

death, 

a life-threatening adverse event, 

inpatient hospitalization or prolongation of existing hospitalization, 

a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 

a congenital anomaly/birth defect, or

An important medical event that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples 
of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result 
in inpatient hospitalization, or the development of drug dependency or drug abuse.
Severity
Adverse events will be graded according to [name grading scale, e.g. CTCAE v5.0]. For AEs 
not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 

Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 

Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning.

Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating.  Of note, the term “severe” does not necessarily equate to 
“serious”.
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*An adverse event may be graded as severe but still not meet the criteria for a Serious 
Adverse Event (SAE).  Similarly, an adverse event may be graded as moderate but still meet 
the criteria for an SAE.  It is important for the PI to consider the grade of the event as well as 
its “seriousness” when determining whether reporting to the IRB is necessary.
Relationship to Investigational Product
All AEs must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below. 
In a clinical trial, the study product must always be suspect.

Definitely Related – There is clear evidence to suggest a causal relationship, and 
other possible contributing factors can be ruled out. The clinical event, including an 
abnormal laboratory test result, occurs in a plausible time relationship to study 
intervention administration and cannot be explained by concurrent disease or other 
drugs or chemicals. The response to withdrawal of the study intervention 
(dechallenge) should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge procedure if 
necessary.

Probably Related – There is evidence to suggest a causal relationship, and the 
influence of other factors is unlikely. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable time after administration of the 
study intervention, is unlikely to be attributed to concurrent disease or other drugs or 
chemicals, and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition.

Potentially Related – There is some evidence to suggest a causal relationship (e.g., 
the event occurred within a reasonable time after administration of the trial 
medication). However, other factors may have contributed to the event (e.g., the 
participant’s clinical condition, other concomitant events). Although an AE may rate 
only as “possibly related” soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or “definitely related”, as 
appropriate.

Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study intervention administration makes a causal 
relationship improbable (e.g., the event did not occur within a reasonable time after 
administration of the study intervention) and in which other drugs or chemicals or 
underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments).

Not Related – The AE is completely independent of study intervention administration, 
and/or evidence exists that the event is definitely related to another etiology. There 
must be an alternative, definitive etiology documented by the clinician.
Expectedness
The Principal Investigator will be responsible for determining whether an AE is expected or 
unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information previously described for the study 
intervention.
Reporting
For studies conducted under an IND, there are two types of Safety Reports submitted to 
FDA:
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
7-Calendar-Day FDA Telephone or Fax Report:  The sponsor-investigator will directly 
notify the FDA, within 7 calendar days after initial receipt of the information, of any 
adverse event that is fatal or life-threatening, unexpected, and considered at least 
possibly related to the investigational product. 

15-Calendar-Day FDA Written Report:  The sponsor-investigator will directly notify 
the FDA within 15 calendar days after initial receipt of the information, of any serious 
adverse event (other than those that are fatal or life-threatening) that is unexpected 
and considered at least possibly related to the investigational product.
Serious Adverse Events which do not meet the criteria for expedited reporting will be 
reported to the FDA in the IND Annual Report.
Plan for reporting Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs), 
including Adverse Events, to the IRB.
The principal investigator will report the following types of events to the IRB:  
Any incident, experience or outcome that meets ALL 3 of the following criteria:
1)  Is unexpected (in terms of nature, specificity, severity, or frequency) given (a) the 
research procedures described in the protocol-related documents, such as the IRB-
approved protocol and informed consent document and (b) the characteristics of the 
subject population being studied; AND 
2)  Is related or possibly related to participation in the research (possibly related means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); AND
3)  Suggests that the research places subjects or others at greater risk of harm 
(including physical, psychological, economic, legal, or social harm) than was 
previously known or recognized.
1.
UPIRSOs may be medical or non-medical in nature and include – but are not 
limited to – serious, unexpected, and related adverse events and 
unanticipated adverse device effects.  Please note that adverse events are 
reportable to the IRB as UPIRSOs only if they meet all 3 criteria listed above.
These UPIRSOs/SAEs will be reported to the IRB in accordance with IRB Policy 710, using 
the appropriate forms found on the website. All related events involving risk but not meeting 
the prompt reporting requirements described in IRB Policy 710 should be reported to the IRB 
in summary form at the time of continuing review. If appropriate, such summary may be a 
simple brief statement that events have occurred at the expected frequency and level of 
severity as previously documented.  In lieu of a summary of external events, a current DSMB 
report can be submitted for research studies that are subject to oversight by a DSMB (or 
other monitoring entity that is monitoring the study on behalf of an industry sponsor).
7. Plan for reporting adverse events to co-investigators on the study, as appropriate the 
protocol’s research monitor(s), e.g., industrial sponsor, DSMBs, study sponsors, funding and 
regulatory agencies, and regulatory and decision-making bodies.
For the current study, the following individuals, funding, and/or regulatory agencies will be 
notified (choose those that apply):
x All Co-Investigators listed on the protocol.
x NIH/NIAAA
x Food and Drug Administration (Physician-Sponsored IND #137044)
x Study Sponsor (John Krystal, MD) and Novartis
x Center for Translational Neuroscience on Alcoholism (CTNA) DSMB 
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The principal investigator, Suchitra Krishnan-Sarin, will conduct a review of all adverse 
events upon completion of every study subject. She will evaluate the frequency and severity 
of the adverse events and determine if modifications to the protocol or consent form are 
required.
Adverse events that meet the criteria for a Serious Adverse Event will be reported to the 
IRB, NIAAA, the CTNA DSMB, study investigators, and to Novartis (the company providing 
mavoglurant) within 24 hours by phone or fax and in writing within 1 week. 
9.2.2
Pharmacokinetics (if applicable)
Pharmacokinetic testing will be done to determine levels of mavoglurant in plasma.  Blood 
will be drawn for this purpose at the first lab session (prior to initiation of mavoglurant) and 
twice at the 2nd lab session (after final dose of mavoglurant and again after alcohol drinking 
session.  Language of this testing is included in the study informed consent form.  A contract 
with Veeda Clinical Research Labs in Gujarat, India has been set up an specimen will be 
shipped appropriately upon study completion.
9.2.3
Biomarkers (if applicable)
N/A
9.3
Study Procedures
Recruitment, baseline assessments, physical exam, and psychological evaluation
Potential subjects will be recruited via posted advertisements in the local newspaper and 
brochures and other materials distributed in the community.   We will also recruit via online 
methods such as FaceBook, CraigsList, online newspapers, Google Ads, etc. They will be 
initially screened for eligibility either by phone after giving verbal consent or via an online 
screener, the link for which will be provided in the study advertisements. After providing 
consent, participants will be asked to give their contact information so that they can be 
contacted regarding their eligibility. They will then proceed to complete the survey, which will 
be housed in a different account on Qualtrics, a secure website.  
Based on eligibility, participants will be scheduled for an intake appointment and complete 
consent via REDcap (or mail or in-person if necessary). All questionnaires, medical history, 
and psychological evaluation will be conducted remotely via video chat (e.g. Zoom, 
FaceTime, etc). If the study participant does not have internet access or a device capable of 
this form of communication, we will conduct the appointment over the phone or in person. 
Each participant will be asked comprehension questions to ensure they understand the 
study and will be asked to sign the consent form. Prior to all in person study appointments, 
COVID-19 screening questions will be asked. All participants will receive a signed copy of 
the consent form to retain for their records. The research assistant will schedule a physical 
exam, including an EKG, routine laboratory work, and hepatic, kidney and thyroid function 
tests.  A detailed medical history will be obtained from all subjects and pregnancy tests for all 
females.   Subject characteristics and medical history will be reviewed by the PI to ensure that 
the subject meets all the eligibility criteria.  The study physician (Dr. Julia Shi) will review their 
eligibility based on their medical history and EKG.  
The psychological evaluation will be completed and reviewed by a licensed psychologist 
after all inventories/assessments are collected. If a subject is deemed at risk, or 
questionable, at the time of the evaluation, the clinical psychologist will be contacted 
immediately and asked to reach out to the participant as soon as possible.  
Lab Session 1 
See appendix for detailed procedure sheet.  Participants will arrive at the Hospital Research 
Unit (HRU), Church Street Research Unit (CSRU), or Masonicare at 8:15am.  We will collect 
BAC, urine toxicology, and conduct paper and pencil baseline questionnaires. At 9:00am, 
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participants will be provided breakfast. They will then complete additional study 
assessments. We will put an IV catheter in the participant’s arm at 11:00am and we will draw 
the initial set of labs. At 12:00pm, participants will be given their first drink of 80-proof vodka 
with a non-carbonated mixer of their choice and will be instructed to drink it in 15 minutes. 
They will continue to receive successive doses of alcohol in 6 equal portions (every 15 
minutes) over a 90-min period designed to raise their blood alcohol levels to 80 mg/dl; we 
chose this dose because this the legal limit of intoxication and is close to the peak BAC we 
have observed in prior ADP sessions (with approx. 200 heavy drinkers) and is similar to the 
alcohol dose used in a previously completed similar protocol with another drug (HIC 
#0602001068).  Alcohol dosing will be calculated using published gender specific algorithms 
based on estimated body water determined from height, weight (obtained at physical exam), 
and age and translated into ml of 80-proof vodka (Curtain & Fairchild, 2003). Regardless of 
the amount of vodka required, the amount of mixer will be adjusted so that the total volume 
of fluid will be constant. These methods of alcohol administration have been safely used by 
our group (Jatlow, et al., 2014), with volunteers who had similar drinking profiles. At 
12:15pm, a blood pressure cuff will be placed on his/her arm to monitor vitals throughout the 
lab session. Safety labs will be drawn and blood samples will be collected at regular intervals 
(at baseline and every 15 minutes during the lab session and then hourly for the next 3 
hours) to assess blood alcohol levels and to assess Mavoglurant levels. They will complete 
paper and pencil questionnaires about mood, medication and alcohol effects at regular time 
intervals, as well as the Body Sway Task.
At 2pm, subjects will be given lunch and will be monitored for any remaining alcohol effects. 
BAC levels will be taken every 30 minutes until the level falls to less than .02 (about 4 
hours). Participants will be allowed to leave when their BAC falls to below .02 or at 6pm, 
whichever comes first. All participants will be provided with transportation to and from lab 
session. 
Outpatient Treatment 
At the commencement of drinking session 1, participants will be sent home with the study 
medication for the full period. If their second lab session is not scheduled within the 
designated timeframe, the participant will come in for their first medication appointment and 
be sent home with their medication that day. They will take their medication daily (in person 
or on video chat – 10min) at approximately 10am. They will be observed taking the study 
medication, for 7-10 days (to achieve steady state levels). This will ensure compliance with 
medication and allow us to monitor side effects daily.  The last dose of study medication will 
be at 8:15 on the morning of their Lab Session 2. Participants will be asked to abstain from 
alcohol during the outpatient medication period; our rationale for requiring this is because 
this is a study to examine alcohol-drug interactions and we want to study these interactions 
in a controlled laboratory session.  
Lab Session 2
See appendix for detailed procedure sheet.  Participants will arrive at the Hospital Research 
Unit (HRU), Church Street Research Unit (CSRU), or Masonicare at 8:15am.  They will be 
instructed to take their last dose of study medication. We will collect BAC, urine toxicology, 
and provide them with breakfast. Following breakfast, they will complete study 
assessments/questionnaires. We will put an IV catheter in the participant’s arm at 11:00am 
and we will draw the initial set of labs. At 12:00pm, participants will be given their first drink 
of 80-proof vodka with a non-carbonated mixer of their choice and will be instructed to drink 
it in 15 minutes. They will continue to receive successive doses of alcohol in 6 equal portions 
(every 15 minutes) over a 90-min period designed to raise their blood alcohol levels to 80 
mg/dl. Safety labs will be drawn and blood samples will be collected at regular intervals (at 
baseline and every 15 minutes during the lab session and then hourly for the next 3 hours) 
to assess blood alcohol levels and to assess Mavoglurant levels. They will complete paper 
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and pencil questionnaires about mood, medication and alcohol effects at regular time 
intervals, as well as the Body Sway Task.
At the end of the drinking session, the participant will be given lunch. They will be monitored 
for any remaining medication and alcohol effects. BAC levels will be taken every 30 minutes 
until the level falls to less than 0.02 (about 4 hours). Participants will be allowed to leave at 
approximately 6pm or when their BAC falls to below 0.02. All participants will be provided 
with transportation to and from lab session.  The following morning participants will go to 
Quest for a blood draw and urine collection.
Follow Up Interviews
Subjects will receive phone calls on the two days following lab session 2 to see how they are 
doing and to assess any remaining side effects from the medication. Subjects will also 
participate in a 30-minute follow-up interview at one week after lab session 2.  During this 
appointment, we will assess participants for any lingering side effects of the medication and 
obtain information about their drinking over the follow up period.  
Payments for Participation (Economic Considerations)
Subjects will have the opportunity to receive up to $630 for completing all parts of the study. 
Payment for the intake interview will be $50. They will receive an additional $65 for the 
physical examination/ in-person intake and up to $20 for completing the MSDM task.  
Subjects will also receive $140 for participating in the 1st laboratory session and $200 for 
completing the 2nd laboratory session. Additionally, subjects will receive $10 to take their 
study medication dose (7-10 days), for up to a total of $100 and $25 for the blood draw the 
morning after the second drinking session. Subjects will be paid $30 for completing the one 
week follow-up appointment. If a subject is asked to come back in for a repeat lab 
appointment (blood work or EKG), he/she will be paid $25. Subjects will be reimbursed for 
parking.
9.3.1
Study Schedule
The study will consist of five parts: 1) Eligibility: Informed consent is obtained, and eligibility 
is evaluated, 2) Lab Session 1: Eligible subjects will be seen outpatient for Lab 1 where we 
will obtain baseline information and randomization to study medication. 3) Outpatient 
Medication: Subjects will be seen (virtually or in-person) on a daily basis, for 6-9 days, to 
take their study medication, 4) Lab Session 2: Subjects will again be seen outpatient for their 
second lab session. They will have their blood drawn and a urine collection the following 
morning. 5) Follow Up Interviews: We will follow up with participants via phone, for two days 
after lab session 2. They will be seen, one week after last session 2 for bloodwork, urine 
collection, and to assess for any potential remaining side-effects.
Phase/Day
Visits
Comments
BL
Initial Intake Screening 
Informed consent obtained prior to any study 
procedures.
BL
Physical Exam 
Includes vitals, blood, urine, EKG, and medical 
history.
Day 0
Lab Session #1 
Randomized to drug condition, vitals, blood, and 
urine
Days 1-10*
Medication 
Administration 
1x/day staff observing subject administering 
medication.
Day 7-10*
Lab Session #2
Last dose of study medication, vitals, blood, and 
urine
Day 8-11
Morning After LS 2
Blood and urine analysis
FU
1 week Follow Up 
Including final blood and urine analysis.
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*Medication taken for 7 to 10 days (pending schedule); Lab #2 occurs on day of last 
medication administration
9.3.2
Informed Consent
At the first screening visit, candidates will meet with a Research Assistant and receive an 
explanation of the study purpose and requirements. If still interested, the candidate will be 
given an opportunity to review, inquire about, and sign the study informed consent form 
approved by the IRB. Subjects must have a breath alcohol level (BAL) of 0.000 measured by 
breathalyzer when signing the informed consent document (tested shortly before or just after 
providing consent). Repeat measurements of BAL are permitted at the discretion of the 
investigator. If appointment is conducted remotely, we will be unable to collect BAL levels.  
Subjects will be given a copy of the signed informed consent form.
9.3.3
Screening
Screening will take place over two visits.  At the initial visit, conducted remotely when 
possible, an interview and self-report assessments will be obtained and study schedule of 
visits will be reviewed.  If the subject appears eligible after this visit, a second in-person 
screening visit will be scheduled where we will conduct a physical exam and additional 
assessments/questionnaires. Final eligibility will be determined by the PI and study 
Physician.  If a subject screen fails, they may be rescreened at the discretion of the PI (and 
consultation with Study Physician, if applicable).
9.3.4
Enrollment 
After a subject has been consented, screened, and meets eligibility criteria they will be 
scheduled for the first Lab Session. This will be done by consulting with the subject’s 
schedule and room availability.  Scheduling of the Medication Administration Days and the 
second Lab Session will also be considered at the time of enrollment due to the flow of study 
these following study visits being interdependent. 
9.3.5
On Study Visits
 
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9.3.6
End of Study and Follow-up
After the second lab session staff will check in with the subject via phone.  A final, follow-up 
visit will be conducted.  Adverse events will be monitored 1 week after the second lab 
session.  The participant will come in-person for blood, along with psychophysiological safety 
measures (heart rate, blood pressure, etc.) only when blood pressure is signfically elevated 
at lab session.  If a subject request a copy of results (e.g. blood analytes), I de-identified 
copy will be provided upon approval of the PI.
9.3.7
Removal of subjects
Each subject has the right to withdraw consent and withdraw from the study at any time. In 
addition, the investigator may find it necessary to discontinue a subject for any reason, 
including the occurrence of an AE or noncompliance with the protocol.
In the event that a subject withdraws or is discontinued from the study, the reason(s) for the 
discontinuation from the study will be recorded and the subject will be asked to return for 
their follow-up visit to obtain final safety measures.
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9.4
Statistical Method
9.4.1
Statistical Design
This study is exploratory in nature and seeks to determine effect sizes to be used in 
subsequent years, in the larger-scale studies, and to determine if alcohol and mavoglurant 
can be safety used together.  Therefore, no formal power calculations have been performed. 
The design employed here, including the chosen sample size, are relatively standard in pilot 
studies (Galasko et al., 1997; Sinha, et al., 1999) 
9.4.2
Sample Size Considerations
As noted above, due to the exploratory nature of this pilot study, the chosen sample size is 
relatively standard in pilot studies.
9.5
Planned Analyses
9.5.1
Primary Objective Analysis
Adverse events will be tabulated and rated for severity (mild, moderate, and severe) and for 
relation to the study intervention (unlikely, possibly, probably, and likely). Area under the 
curve will be measured for blood alcohol levels and compared between the two sessions 
(mavoglurant; baseline no-drug).  Changes in serum chemistries, blood cell counts, and 
urinalysis will be compared before and after alcohol consumption between sessions (on 
drug, baseline no-drug).  Quantitative outcomes will be analyzed using mixed models.
9.5.2
Secondary Objectives Analyses
Drug plasma levels for mavoglurant will be compared before and after alcohol consumption.
9.5.3
Exploratory Objectives Analyses (if applicable)
Changes in subjective and cognitive motor performance measures following alcohol 
consumption will also be compared between sessions (on drug, baseline no-drug).
9.5.4
Safety 
Not Applicable.  Evaluation of safety is already a main object for this study.
9.5.5
Analysis of Subject Characteristics
Subject demographics will be collected and reported, noting any differences between 
active/placebo groups.
9.5.6
Interim Analysis (if applicable)
Not Applicable
9.5.7
Health economic evaluation
Not Applicable
9.5.8
Other
Not Applicable
9.5.9
Subsets and Covariates
Not Applicable
9.5.10 Handling of Missing Data
Mixed effects models will use all available data on individuals. Dropout rates will be 
compared between treatment groups and reasons for dropout will be evaluated in order to 
inform future studies.
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10  Trial Administration
10.1  Ethical Considerations: Informed Consent/Assent and HIPAA Authorization
The study will be conducted under the ethical principles as described in 45 CFR § 46.111 
and ICH GCP.
At the start of the intake session, all subjects will receive an explanation of the study 
including its risks, benefits, and procedures, and will be given an opportunity to withdraw 
from the study. Following the resolution of any questions, the subject will be asked to sign 
the consent form, if he/she agrees to participate.  The consent form also includes language 
required for HIPAA Authorization.
Given that this research study is not a treatment study, there are no treatment alternatives, 
however subjects can decline participation.
Subjects will be paid an amount that approximates $20/hour for study visits.
10.2 Institutional Review Board (IRB) Review
The protocol will be submitted to the IRB for review and approval. Approval of the protocol 
must be obtained before initiating any research activity. Any change to the protocol or study 
team will require an approved IRB amendment before implementation.  The IRB will 
determine whether informed consent and HIPAA authorization are required.  
The IRB will conduct continuing review at intervals appropriate to the degree of risk, but not 
less than once per year.
A study closure report will be submitted to the IRB after all research activities have been 
completed.   
Other study events (e.g. data breaches, protocol deviations) will be submitted per Yale’s 
Human Investigation Committee/Human Research Protection Program policies.
10.3 Subject Confidentiality
Subject confidentiality is held in strict trust by the research team.  Subject medical record 
review will be limited to the just the elements needed to complete the study.  Only authorized 
HIPAA and GCP trained study team members will have access to these records.
This study has a Certificate of Confidentiality.  Subjects are informed of what this means and 
what it covers and its limitations in the informed consent document.
Each subject will be assigned a unique study number. A master list linking the unique study 
number to the human subject will be maintained in a locked drawer at our offices at 34 Park 
St in New Haven
Data will be stored on an encrypted password protected Yale ITS managed workstation 
without any HIPAA identifiers. Strict confidentiality will be maintained in all records of the 
study by identifying subjects by code numbers. Information that is obtained in connection 
with this study and that can be identified with a subject will be kept confidential (subject’s 
charts are kept in a locked room and file cabinet. Files will be kept in locked cabinets in a 
security system protected office. All information obtained from subjects is referred to by code 
number and kept in locked confidential files (subjects’ paper charts are kept in an area 
protected with a security system, in a locked room and file cabinet). Any published results 
are published as group data without the use of characteristics that would identify individual 
subjects. We quote information only by number in conference discussions, scientific reports 
or publications to maintain anonymity.
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10.4 Deviations/Unanticipated Problems
If the study team becomes aware of an anticipated problem (e.g. data breach, protocol 
deviation), the event will be reported to the Yale HIC via IRES.  If deviations occur study staff 
will follow Yale HIC guidelines for reporting (i.e. immediately or at annual continuing review 
of the protocol).
10.5 Data Collection
As required by law, all reasonable efforts will be made to protect the confidentiality of 
subjects’ protected health information, which may be shared with others to support this 
research, to conduct public health reporting, and to comply with the law as required 
(according to a HIPAA compliant research authorization form signed by the subject). Yale 
Staff will collect required research data through study procedures as outlined in this protocol 
and record it in confidential research records and protected computer files. Each subject will 
have a paper “research chart” created for this information, which will be kept in a locked 
room and file cabinet. In all study records (except for the subject’s research chart which 
includes the subject’s name and other unique identifiers and all original records received by 
Yale with such identifiers), subjects will be referred to by a code number (with access to 
codes restricted to research staff).
Data will be stored on an encrypted password protected laptop computer without any HIPAA 
identifiers. Strict confidentiality will be maintained in all records of the study by identifying 
subjects by code numbers. Information that is obtained in connection with this study and that 
can be identified with a subject will be kept confidential (subject’s charts are kept in a locked 
room and file cabinet). Files will be kept in locked cabinets in a security system protected 
office. 
All information obtained from subjects is referred to by code number and kept in locked 
confidential files (subjects’ paper charts are kept in an area protected with a security system, 
in a locked room and file cabinet). Any published results are published as group data without 
the use of characteristics that would identify individual subjects. We quote information only 
by number in conference discussions, scientific reports or publications in order to maintain 
anonymity. 
Patient health information obtained by this study is confidential and may only be disclosed to 
third parties as permitted by the Compound Consent and Authorization form signed by the 
patient or unless permitted or required by law. Medical information may be given to a 
patient’s personal physician or other appropriate medical personnel responsible for the 
patient’s welfare for treatment purposes as permitted by an Authorization for 
Access/Release of Health Information form signed by the patient. Medical records that 
identify subjects and the consent form signed by subjects must be available for inspection 
upon request by representatives of the U.S. FDA and other regulatory agencies, national 
and local health authorities, the study investigators, the sponsor and the sponsor’s 
representatives and collaborators, and the local IRB. Only research personnel will have daily 
access to the research records.
Although considered unlikely to be encountered, limits to confidentiality such as mandatory 
reporting requirements for abuse of children or the elderly will be complied with. Subjects will 
be notified of this mandatory reporting in the consent form.
10.6 Data Quality Assurance
All study staff will be trained to ensure accurate and consistent data collection.  Data will be 
regularly checked by the study data manager to ensure validity and completeness.  In 
addition, all study staff will keep up to date with all Good Clinical Practice and Human 
Research Protection trainings.
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10.7 Study Records
Study records include IRB documents (protocol, consent forms, etc), IND documents 
(amendments, annual reviews, etc), a study subject binder consisting of de-identified source 
documents/case report forms, and a separate subject folder consisting research documents 
that may contain identifiable information (consent documents, subject contact information, 
study nurse/physician notes, etc) and is kept separately under lock and key.
10.8 Access to Source Documents
Source documents will be contained in study binders.  This study will use Teleforms data 
entry software (using specific forms that are scannable into a database).  As the 
binders/source documents are completed, research staff will provide the study data manager 
with the forms.  They will then be scanned, validated uploaded into study specific databases.
10.9 Data or Specimen Storage/Security
Data will be stored on an encrypted password protected laptop computer without any HIPAA 
identifiers. Strict confidentiality will be maintained in all records of the study by identifying 
subjects by code numbers. Information that is obtained in connection with this study and that 
can be identified with a subject will be kept confidential (subject’s charts are kept in a locked 
room and file cabinet. Files will be kept in locked cabinets in a security system protected 
office. All information obtained from subjects is referred to by code number and kept in 
locked confidential files (subjects’ paper charts are kept in an area protected with a security 
system, in a locked room and file cabinet). Any published results are published as group 
data without the use of characteristics that would identify individual subjects. We quote 
information only by number in conference discussions, scientific reports or publications to 
maintain anonymity.
Study data will periodically submitted to NIH National Data Archive (NDA; 
https://nda.nih.gov/).  Grant recipients must include language in the informed consent form, 
agreeing that data and supporting documentation submitted to NDA may be accessed and 
used broadly by approved users for research.  This submitted data is de-identified.  
Language to be included follows:
Data from this study will be submitted to the National Institute of Mental Health Data Archive (NDA) at 
the National Institutes of Health (NIH). NDA is a large database where deidentified study data from 
many NIH studies are stored and managed. Sharing your deidentified study data helps researchers 
learn new and important things about brain science more quickly than before.
Deidentified study data means that all personal information about you (such as name, address, 
birthdate and phone number) is removed and replaced with a code number. The study researchers 
will have to collect your personal information from you in order to make that code number. The code 
number cannot be used to identify you. The study researchers will never send your personal 
information to NDA.          
It is possible that you will participate in more than one study that sends data to NDA. NDA can 
connect your data from different studies by matching the code number on your deidentified data from 
each study. This data matching helps researchers who use NDA data to count you only one time. It 
also helps researchers who use NDA to better understand your health and behavior without knowing 
who you are.                                                        
During and after the study, the study researchers will send deidentified study data about your health 
and behavior to the NDA. Other researchers across the world can then request your deidentified 
study data for different research projects. Every researcher (and the institution to which they belong) 
who requests your deidentified study data must promise to keep your data safe and promise not to try 
to learn your identity. Experts at the NIH who know how to keep your data safe will review each 
request carefully to reduce risks to your privacy. Sharing your study data does have some risks, 
although these risks are rare. Your study data could be accidentally shared with an unauthorized 
person who may attempt to learn your identity. The study researchers will make every attempt to 
protect your identity.
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You may not benefit directly from allowing your study data to be shared with NDA. The study data 
provided to NDA may help researchers around the world learn more about brain science and how to 
help others who have problems with brain science. NIMH will also report to Congress and on its 
website about the different studies using NDA data. You will not be contacted directly about the study 
data you contributed to NDA. 
You may decide now or later that you do not want your study data to be added to NDA. You can still 
participate in this research study even if you decide that you do not want your data to be added to 
NDA. If you know now that you do not want your data in NDA, please tell the study researcher before 
leaving the clinic today. If you decide any time after today that you do not want your data to be added 
to NDA, call or email the study staff who conducted this study, and they will tell NDA to stop sharing 
your study data. Once your data is part of NDA, the study researchers cannot take back the study 
data that was shared before they were notified that you changed your mind. If you would like more 
information about NDA, it is available on-line at http://nda.nih.gov.
10.10 Retention of Records
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an International Conference on Harmonisation (ICH) region and 
until there are no pending or contemplated marketing applications in an ICH region or until at 
least 2 years have elapsed since the formal discontinuation of clinical development of the 
study intervention. These documents should be retained for a longer period, however, if 
required by local regulations. No records will be destroyed without the written consent of the 
sponsor, if applicable. It is the responsibility of the sponsor to inform the investigator when 
these documents no longer need to be retained.  The company supplying the study 
medication (Novartis) will also be consulted on destruction of study materials.
10.11 Study Monitoring
Clinical site monitoring is conducted to ensure that the rights and well-being of trial 
participants are protected, that the reported trial data are accurate, complete, and verifiable, 
that the facilities and staffing are adequate for continued study conduct, and that the conduct 
of the trial is in compliance with the currently approved protocol/amendment(s), with 
International Council for Harmonisation Good Clinical Practice (ICH GCP), and with 
applicable regulatory requirement(s) including federal, state and local regulations and 
institutional policies and procedures. 
Clinical site monitoring will be performed by the Yale Center for Clinical Investigation (YCCI). 
Monitoring visits will include a site initiation visit, regularly scheduled on-site interim 
monitoring visits and/ or remote interim monitoring visits while subjects are on study, and a 
site close-out visit at the site. Following each monitoring visit, a visit report will be generated 
containing information on site activities and a summary of pertinent points and action items. 
The report will be provided with a follow-up letter. Site-specific data status reports will be 
distributed to the site regularly to outline planned, missing or incomplete case report forms 
and any outstanding data queries.
During monitoring visits, the following may be reviewed:
•
Protection of the rights, safety and welfare of subjects through review of informed 
consent process and documentation, adverse events (AEs) and serious adverse 
events (SAEs) and safety procedures
•
Subject eligibility
•
Source verification
•
Protocol compliance
•
Deviations and Non-compliance
•
Investigator Site File
•
ICH GCP compliance
•
Investigational Drug/ Device Storage and Accountability (including quantity and 
disposal procedures)
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•
Laboratory Facilities
•
Equipment maintenance and calibration
•
Additional study supplies inventory and assessment
•
Study progress and/or follow-up on issues with Site Principal Investigator (PI) and 
relevant members of the study team
The Study PI and YCCI will define the required study monitoring activities in a Clinical 
Monitoring Plan (CMP). The CMP describes in detail who will conduct the monitoring, at 
what frequency monitoring will be done, at what level of detail monitoring will be performed, 
and the distribution of monitoring reports.
10.12 Data Safety Monitoring Plan
This protocol is a moderate risk protocol and therefore requires a data safety and monitoring 
plan.
The principal investigator will be responsible for monitoring the data, assuring protocol 
compliance, and conducting the safety reviews at the specified frequency, which must be 
conducted at a minimum of every 6 months (including when reapproval of the protocol is 
sought).  During the review process, the principal investigator will evaluate whether the study 
should continue unchanged, require modification/amendment, or close to enrollment. Either 
the principal investigator, the IRB, Novartis, or the CTNA DSMB have the authority to stop or 
suspend the study or require modifications.
We will be accessing the Data and Safety Monitoring Board (DSMB) developed for the 
Center for Translational Neuroscience on Alcoholism (John Krystal, PI) since this project is a 
component within this Center.  The DSMB is multi-disciplinary and includes representatives 
with expertise in the primary components of the proposed trial. The following individuals will 
be on the DSMB as voting members:
Robert Swift, MD, PhD.,Prof Psych (Brown)/ASOS Res Provid. VAMC Chmn, DSMB, Robert 
Stout, PhD., Director, Decision Sci. Int., Statistician, DSMB, Howard Zonana, MD., Dir, Dept 
Psychiatry Ethics Committee, IRB Rep, DSMB, Lisa Newton, PhD., Prof. Applied Ethics, 
Fairfield Univ. Ethicist, DSMB
This DSMB will follow the operational guidelines outlined in the YCCI OR CNRU plan for 
DSMB. We hope to recruit subjects at a maximum rate of 5-10 per month, thus, the DSMB 
will review safety reports two times a year. More frequent meetings will be scheduled if 
indicated by interim findings.
10.13 Study Modification
All study modifications will be determined by the study PI.  Modifications will be submitted to 
Yale HIC (IRB) for approval prior to being implemented.  Upon approval from IRB, the 
Sponsor and FDA will be notified of all modifications.
10.14 Study Discontinuation
If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will 
provide the reason(s) for the termination or suspension.  Study participants will be contacted, 
as applicable, and be informed of changes to study visit schedule.
 Circumstances that may warrant termination or suspension include, but are not limited to:

Determination of unexpected, significant, or unacceptable risk to participants

Demonstration of efficacy that would warrant stopping   

Insufficient compliance to protocol requirements

Data that are not sufficiently complete and/or evaluable

Determination that the primary endpoint has been met
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
Determination of futility
10.15 Study Completion
The study PI and Sponsor will determine the completion of the study with regards to targets 
for enrollment and study completers.  Upon completion, IRB (Yale HIC) and FDA will be 
notified appropriately.
10.16 Conflict of Interest Policy
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will 
be required to have such conflicts managed in a way that is appropriate to their participation 
in the trial. The study leadership in conjunction with the appropriate conflict of interest review 
committee has established policies and procedures for all study group members to disclose 
all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest.
All investigators will follow the applicable conflict of interest policies.
10.17 Funding Source
This study is being conducted as part of the Center for the Translational Neuroscience of 
Alcoholism (CTNA-5) which is funded by a grant from National Institute on Alcohol Abuse 
and Alcoholism / NIH / DHHS (#2P50AA012870-21).
10.18 Publication Plan
Any resulting publications will be done with approval of the PI, Sponsor, and Novartis.
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11 Appendices
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TIME
START OF DRINKING SESSION PROCEDURES
Prior to 
arrival
RA
___ Confirm Dr. Shi signed off on EPIC orders
___ Confirm participant breakfast and lunch were ordered from HRU and transport was 
setup.
___ Confirm covid questions were filled and negative rapid covid test and send both to 
Lindsey.douglas@yale.edu and lynda.knaggs@ynhh.org. 
___ Pick up study alcohol and meds from IDS 
___ Bring to lab: alcohol, participant binder, participant folder, CTNA laptop, fruit juice 
mixer and frozen breakfast option (if needed).
___ Confirm participant was added to OnCore 
8:15 am
RA
*RA and participant to have a mask on in lab (confirm extra masks are at lab)
____ Give participant meds (if first dose is scheduled for tomorrow)
Meet participant in 1st floor lobby and walk them to the CSRU on the 4th floor
____ Get study cart from OnCore/Epic Suite #404, code 9224#, Key holder (PIN 3636)
Urine drug screen and pregnancy test (*RA to send urine to Quest):  Neg _____ Pos 
_____ 
Record time of last drink   _____________   Amount of last drink ____________
Instruct participant on using both (BAC and CO) step out of room. 
BAC Level: _____________       CO Level: ____________  
*If BAC is positive, notify Dr. Krishnan-Sarin 860-575-9895
____ Concurrent medications, TLFB, SAFTEE 
Collect subject’s cigarettes (if applicable)            Smoker: _____        Nonsmoker: _____   
Height:___________ inches (Shoes off)      Weight: ___________ kgs.   ___________ 
lbs.
      *For data only. IDS will be using height and weight from PE for alcohol calculations.
____ Fill out Quest form for today
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Baseline PACKET #1: YCS Long, AES, BAES, BIS, BIS/BAS, UPPS, SRHI, PROMIS 
Sleep 
and Impairment Measures, AUDIT-C, W9
Baseline Assessments 
____ Body Sway Task  (Confirm data is recording and showing weight, if not restart 
task)
____ CPT
____ SRT
____ CRT
9:00 am
RA
Give subject breakfast. Time: _______ (Ensure they eat, so they don’t have an empty 
stomach)
*NO FOOD AFTER 10AM, UNTIL AFTER DRINKING SESSION IS OVER
11:00 am
NURSE
Place heplock in non-dominant arm (DO NOT USE A RUNNING IV)
*If you experience any problems or have any concerns with the IV placement, please 
contact study staff PRIOR to placing IV. 
Record actual time of blood draw: ________
____  DRAW “-60min” BAL (blue microtube)
____ Health Profile (CMP, CBC w/diff, TSH, Phosporous, Magnesium, Uric Acid) 
2 Marble/gold 5ml top tubes (spun) and 1 lavender tube 4ml (unspun) *RA to send 
samples Quest
____ 1 MAV lavender 10ml pre “-60” plasma level. Put two lables on tube. Process in 
cold centrifuge (-80 degrees freezer or dry ice)
____ Urine (Urinalysis) *RA to send samples to Quest 
11:00 am
RA
____ Place labled Health Profile (2 Marble/gold 5ml top tubes (spun), 1 lavender tube 
4ml 
(unspun), and urine sample in Quest box on 4th floor outside of room 401. 
____ Call Quest for pickup or online (ensure they arrive prior to building closing)
Record dose of alcohol from Pharmacist and mixer
       Alcohol Dose (vodka): ___________ ml      Mixer (Juice): _________ ml 
Bathroom break and ensure participant has water to drink.
Premix all 6 drinks Juice (of their choice) and vodka (0.03 mg%) and cap securely. 
Keep drinks on ice.
Setup Zoom on laptop to communicate during drinking session.
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11:55 pm
RA
Bring all 6 drinks into room with participant. Bring packets 2-7 into room.
Set up for drinking session and READ study spiel to subject. 
12:00 pm
RA
Drink #1, Juice (of their choice) and vodka (0.03 mg %)
Instruct participant that s/he has 15 minutes to drink cup #1 and to pace their drinking so 
it is consumed over the entire 15-minute period. (start timer count up)
12:15 pm
NURSE 
BP: _______________    Pulse: _______  (BP cuff on arm opposite IV, stays on until 
the end of 
the drinking session)     
DRAW “+15min” BAL      Record actual time of blood draw: ________ 
12:15 pm
RA
PACKET#2: YCS, AES
Drink #2, Juice (of their choice) and vodka (0.03 mg %)
Instruct participant that s/he has 15 minutes to drink it (start timer)
12:30 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+30min” BAL      Record actual time of blood draw: ________    
12:30 pm
RA
PACKET #3: YCS, AES 
Drink #3, Juice (of their choice) and vodka (0.03 mg %)
Instruct participant that s/he has 15 minutes to drink it (start timer)
12:45 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+45min” BAL      Record actual time of blood draw: ________  
12:45 pm
RA
PACKET #4: YCS, AES, BAES 
Drink #4, Juice (of their choice) and vodka (0.03 mg %)
Instruct participant that s/he has 15 minutes to drink it (start timer)
1:00 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+60min” BAL      Record actual time of blood draw: ________    
1:00 pm
RA
PACKET #5: YCS, AES 
Drink #5, Juice (of their choice) and vodka (0.03 mg %)
Instruct participant that s/he has 15 minutes to drink it (start timer)
1:15 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+75min” BAL      Record actual time of blood draw: ________  
1:15pm
RA
PACKET #6: YCS, AES
Drink #6, Juice (of their choice) and vodka (0.03 mg %)
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Instruct participant that s/he has 15 minutes to drink it (start timer)
1:30 pm
NURSE
Have subject rinse mouth out with water
Breath Alcohol Level: ________     If above 0.02, repeat at 2pm
DRAW “+90min” BAL      Record actual time of blood draw: ________    
1:30 pm
RA
PACKET #7: YCS, AES, BAES 
Post Assessments
____ Body Sway Task (confirm data is recording and showing weight, if not restart task)
____ CPT
____ SRT
____ CRT
____ Give participant snacks for after lunch
 2:00 pm
NURSE
Please wait until participant has finished current task before entering room
BP: _______________    Pulse: _______  
DRAW “+120min” BAL Record actual time of blood draw: ________    
PACKET #8: YCS, AES
Breath Alcohol Level: ________ 
Serve participant Lunch
2:30 pm
NURSE
Breath Alcohol Level: ________     If above 0.02, repeat at 3:00pm
PACKET #9: YCS, AES
3:00 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+180min” BAL Record actual time of blood draw: ________    
PACKET #10: YCS, AES
Breath Alcohol Level: ________     If above 0.02, repeat at 3:30
3:30 pm
NURSE
Breath Alcohol Level: ________     If above 0.02, repeat at 4:00pm
4:00 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+240min” BAL Record actual time of blood draw: ________    
Breath Alcohol Level: ________     If above 0.02, repeat at 4:30pm
4:30 pm
BP: _______________    Pulse: _______  
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NURSE
Breath Alcohol Level: ________     If above 0.02, repeat at 5:00pm
5:00 pm
NURSE
BP: _______________    Pulse: _______  
DRAW “+300min” BAL Record actual time of blood draw: ________    
Remove IV catheter
Breath Alcohol Level: ________     If above 0.02, repeat at 5:30pm
If below .02 please contact RA to arrange participant transportation home.
5:30 pm
NURSE
BP: _______________    Pulse: _______  
Breath Alcohol Level: ________     If above 0.02, repeat at 6:00pm
If below .02 please contact RA to arrange participant transportation home.
6:00 pm
NURSE
BP: _______________    Pulse: _______  
Breath Alcohol Level: ________    
Please contact RA to arrange participant transportation home. 
6:00 pm
RA
Confirm Quest picked up samples from Quest box on 4th floor outside of room 401.
Check on all supplies (drugs tests, pregnancy tests, breathylzer tubes, CO tubes, etc). If 
any thing 
is low resupply.
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COMPOUND AUTHORIZATION AND CONSENT FOR PARTICIPATION IN A RESEARCH 
PROJECT
200 FR. 4 (2014-3) 
YALE UNIVERSITY SCHOOL OF MEDICINE – YALE-NEW HAVEN HOSPITAL
Study Title: A Pilot Study on the Safety and Efficacy of Mavoglurant in Alcohol Drinking
Principal Investigator: Suchitra Krishnan- Sarin, Ph.D., Professor of Psychiatry
Funding Source: National Institutes of Health
Research Study Summary:

We are asking you to join a research study.

The purpose of this research study is to examine the interactions between alcohol and a drug called 
mavoglurant.

Study procedures will include initial intake, remote psychological examination, PE/In-person intake, lab 
session 1, medication period, lab session 2, morning after lab session 2 lab work and 1 week follow up.  

13 (some will be remote) visits are required.

These visits will take approximately 25 hours total. 

There are some risks from participating in this study. Side effects from the study medication, mavoglurant. 
Risks of alcohol consumption. Possible interactions of alcohol and mavoglurant. Possible discomfort in 
answering certain items on questionnaires. Bruising, blood clots or light-headedness from blood draw. 
Irritation of the skin from adhesive used for EKG. Risk for hematoma at the site of the venous puncture 
from Intravenous catheter. Very rarely, venous puncture can also result in a blood clot or infection. 

You will not directly benefit from participating in this study. You may benefit by receiving, at no charge, a 
thorough screening and diagnostic evaluation, the results of which may be shared with you and, if you wish, 
with your physicians.  This research will benefit scientific knowledge and may lead to the development of a 
potential therapy for alcoholism.

Taking part in this study is your choice. You can choose to take part, or you can choose not to take part in 
this study.  You can also change your mind at any time.  Whatever choice you make, you will not lose 
access to your medical care or give up any legal rights or benefits. 

If you are interested in learning more about the study, please continue reading, or have someone read to you, 
the rest of this document. Take as much time as you need before you make your decision. Ask the study 
staff questions about anything you do not understand. Once you understand the study, we will ask you if you 
wish to participate; if so, you will have to sign this form.
Invitation to Participate and Description of Project
You are invited to participate in a small study to examine the interactions between alcohol and a drug called 
mavoglurant. Mavoglurant is an investigational medication that has been studied in a variety of disorders, 
including Obsessive Compulsive Disorder, Parkinson’s and Fragile X Syndrome (genetic condition causing 
intellectual disability, behavioral, and learning difficulties). Since mavoglurant targets a neurochemical system, 
called the glutamate system, which is involved in alcohol’s effects, we want to examine if this drug alters an 
individual’s responses to alcohol. In this project, we will explore the effects of mavoglurant on responses to 
alcohol, including stimulation, sedation, intoxication, and physiological reactions (e.g. blood pressure, heart 
rate, steadiness) You have been chosen to participate because you drink alcoholic beverages socially and are not 
seeking treatment for your alcohol use. You may smoke cigarettes but use no other street drugs. 28 participants 
will complete this project.
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The study is funded by the National Institutes of Health.  In order to decide whether you wish to be a part of this 
research study, you should know enough about its risks and benefits to make an informed decision. This consent 
form gives you detailed information about the research study, which a member of the research team will discuss 
with you. This form will be completed as a hard copy on paper or online through REDCap. This discussion will 
go over all aspects of this research: its purpose, the procedures that will be performed, any risks of the 
procedures and any possible benefits. Once you understand the study, you will be asked if you wish to 
participate; if so, you will be asked to sign this form.
COVID-19 related procedures 
We care about your safety as a research participant. Because participating in this study may involve travel 
outside of your home and exposure to others, we will discuss ways to minimize risks related to COVID-19. All 
study participants must be fully vaccinated against COVID-19 (as defined by CDC guidelines). If you are 
eligible for the study, we will ask that you fill out a COVID symptom online prior to each in person 
appointment. This questionnaire will be sent to you via an online link to your cell phone or email (your 
preference). Depending on symptoms, we may need to call you to follow up on your symptoms. You will not be 
allowed to attend in-person visits until your COVID symptom questionnaires are completed. If you are not able 
to fill out the online questionnaire, study staff can administer the questionnaire via phone. 
At all in-person appointments, participants will be asked to wear masks and study staff will wear masks. If you 
do not have a mask, one will be provided to you by study staff. Further safety information for the sessions is 
described below. During in-person appointments, you will again be asked about COVID symptoms, and a 
temperature check will be conducted. Participants who report symptoms or have a temperature of >100 will be 
asked to reschedule their visit and instructed to immediately contact their primary health care provide or call the 
Campus COVID Resource line (203-432-6604).
Description of Procedures
This study consists of five parts: 1) An evaluation period during which we will determine your eligibility for the 
study, physical exam/in-person intake, and your medical history in your medical record may be reviewed for 
eligibility by the study physician and study psychologist 2) Lab Session 1, during which you will be randomly 
assigned (like flipping a coin) to receive mavoglurant or a placebo (like a sugar pill). 3) Medication Period, in 
which you will attend via video chat daily for 6-9 days, where you will be observed taking the study 
medication. 4) a fourth part in which you will be asked to come in for Lab Session 2 followed by a blood 
draw/urine collection the morning after. 5) The last part is the follow-up appointments.  We will call to see how 
you are doing and check on any remaining side effects. You will return for a brief visit two weeks after you Lab 
Session 2 to have a blood draw, urine collection and your blood pressure evaluated.
1) Remote Evaluation: For the health and safety of everyone, much of the intake will be conducted 
remotely via phone call or videoconferencing. During this appointment, you will provide personal 
information, including your psychological history and your history and current use of alcohol. 
Information will be collected by you filling out questionnaires via a website and the researcher 
administering questionnaires. The researcher will be on the phone and/or video chat with you for the 
entirety of this collection period. Additionally, portions of the clinical examination and physical 
examination (see below) will be collected during this remote visit. It should take approximately 3 hours 
to complete all parts of the remote intake, remote physical, and remote psychological examination. 
Following this, at your convenience, we will schedule an in-person physical examination/intake at 1 
Long Wharf Drive, New Haven, that will include an electrocardiogram, along with blood and urine tests. 
This will require about 2 hours of your time. You will be asked to not use any drugs while you are 
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participating in this study. If you test positive for any drugs or alcohol, you may not be paid for your 
appointment and may be asked to reschedule. Females will have a pregnancy test and will only be 
allowed to participate if the result is negative. The blood tests are routine safety laboratory chemistry 
tests and the urine test will be used for routine lab screening and use of drugs. 
2)  Lab Session 1: If you are found to be eligible, you will enter the second part of the study, lab session 
1. This appointment will be conducted at the HRU at YNHH, CSRU at 2 Church Street South, New 
Haven or Masonicare, 22 Masonic Ave, Wallingford. Since we are giving you alcohol you cannot 
drive to the appointment. You will be provided with transportation to and from the appointment or can 
choose to be dropped off. You will come in at 8:15 am. When you arrive, you will be asked questions 
about your use of alcohol, drugs, and any prescribed medications. We will also collect a urine sample 
to screen for use of drugs (e.g., cocaine, opiates, marijuana, benzodiazepines); this test will have to be 
negative for you to continue in the study. If the drug test is positive, you will need to be rescheduled.   
If you are a smoker, prior to entering the lab you will be given time to smoke a cigarette. You will be 
given breakfast at 9am, complete questionnaires and computer tasks. At approximately 11:00 am, an IV 
will be placed in your non-dominant arm and will be used to draw blood during the session.  This is 
done to avoid having to stick you more than once for the blood collections.  A blood pressure cuff will 
be placed on your other arm to monitor your vital signs (e.g., blood pressure, pulse). 
We will provide you with alcohol to drink from 12:00 pm to 1:30 pm in the form of 6 drinks. These 
drinks will contain 80-proof vodka with a non-carbonated mixer of your choice (based on your 
selection at intake). You will drink beverages containing an amount of alcohol corresponding to 
moderate drinking (approximately 3 drinks for women and 4 drinks for men). The exact amount of 
alcohol given to you will depend upon your body size (height and weight); however, you will not be 
given an amount of alcohol greater than that which you have previously ingested on at least one 
occasion during the past twelve months. We will ask you to consume a drink every 15 minutes. If you 
are unable to consume all of the drinks, you have the right to stop drinking. If you are a smoker, you 
cannot smoke during this session but once it is over you can use nicotine lozenges or gum. 
Blood samples will be obtained to measure blood chemistry before the alcohol drinking session. Blood 
alcohol concentrations will be drawn every 15 minutes for 90 minutes and hourly thereafter. Breath 
alcohol levels will be performed every 30 minutes until the alcohol level has dropped below 0.02 or 
until 6pm. 
We will ask you to complete some questionnaires on how alcohol makes you feel and about your 
mood during each session; these assessments will be completed multiple times during each session. 
We will also assess your balance by having you stand on a balance board as steadily as possible for 30 
seconds before and after drinking. 
Your IV catheter will be removed at approximately 5:00 pm. You will be allowed to rest in your room, 
watch movies, listen to music, and have a snack. You will stay until your BAC falls to below 0.02 or 
until 6pm. At that point you will be provided with transportation home (Uber, Lyft, or Taxi).
3) Medication Period: You will be randomized to receive either mavoglurant or placebo (sugar pill) and 
will receive your supply of study medication upon completion of Lab Session 1.  During the next 6-9 
days, we will video chat with you daily while you take your study medication (200mg of 
mavoglurant/day or a placebo). You will be monitored for any side effects. If you are experiencing 
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excessive side effects, you may be scheduled to meet with the study physician and may be asked to 
discontinue your participation.  We will ask you not to drink any alcohol during this medication period. 
Midway through the medication period you will be required to provide a negative drug test (females will 
also need a negative pregnancy test). An additional test/s will be administered if your first day of 
medication does not take place the day after your first lab session.
4) Lab Session 2: The second laboratory session will be scheduled approximately one week after the first 
lab session, depending on your schedule and room availability. It will be similar to the first lab session 
as far as blood draws, questionnaires, and computer assessments. The main difference will be that you 
will take your final dose of study medication that morning. As with lab session 1, we will be giving 
you alcohol therefore, you cannot drive to the appointment. You can be dropped off or we can arrange 
transportation to the appointment. Your IV catheter will be placed at 11:00 am and alcohol will be 
given to you from 12:00 pm - 1:30 pm. You will stay until your breath alcohol level falls to below 
0.02 or 6pm. You will be provided you with transportation home (Uber, Lyft, or Taxi). You will be 
asked to go to Quest Diagnostics the following morning for a urine collection and blood draw. 
5) Follow Up: We will call you on the two days following the second lab session to briefly check on how 
you are doing and to record any remaining side effects.  
One week after you complete the second lab session, we will video chat with you for a 30-minute 
follow-up interview. We will record any remaining side effects of the medication and ask a few brief 
health-related questions. You will be asked to come in for a brief blood draw, urine collection, and blood 
pressure reading.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this website at any time.
Risks and Inconveniences
The possible risks, discomforts and side effects of the procedures are described below, including safeguards to 
be used for your protection.
Risks Associated with Study Drug, Mavoglurant: Mavoglurant, or AFQ056, has been studied in a total of 1863 
study subjects. Overall, the adverse events observed in the various human studies were of mild to moderate 
severity. Dizziness (11%), visual hallucinations (11.1%), uncontrolled, involuntary movement (12%), 
headaches (8.3%), falls (8%), impaired voluntary movement (8%), and lack of energy (8%) were the most 
common. Other adverse events (5.6%) were anxiety, back pain, confusion, constipation, decreased hemoglobin 
(protein in red blood cells), insomnia, muscle spasms, nasopharyngitis (common cold), nausea, peripheral 
edema (swelling in legs), orthostatic hypotension (decrease in blood pressure when standing), blurred vision, 
have also been observed.  The safety of AFQ056 was also assessed in 50 patients with moderate to severe 
Obsessive Compulsive Disorder. Patients in this study received 200 mg BID (twice the dose being used in the 
current project) of mavoglurant for up to 18 weeks and the results indicate that this dose was safe and well 
tolerated.  
Risks associated with alcohol: Several medical conditions could potentially be worsened by acute alcohol 
administration (e.g., liver disease, cardiac abnormality, pancreatitis, diabetes, neurological problems, and 
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gastrointestinal disorders). Therefore, subjects with evidence of these condition, as revealed by physical exam 
and/or laboratory findings, will be excluded from the study.
Alcohol may also cause nausea in high doses; however, nausea is not expected at the dose being used in this 
sample of healthy volunteers who will report prior experience of consuming alcohol levels similar to the 
quantity used in this study. Alcohol dosing will be calculated using published gender specific algorithms based 
on estimated body water determined from height, weight, and age and the amount of alcohol provided will raise 
your blood alcohol level to 80 mg/dl, which is the legal limit of intoxication.
Another area of potential risk to subjects under the influence of alcohol involves their safety during the 
experimental procedures. Although impairment of gross motor coordination may occur after alcohol 
administration at the doses being used in this study, all experimental procedures will be conducted under the 
supervision of the experimenters to prevent possible accidents such as falls. Further on the day of alcohol 
administration, you will also be observed and questioned until your BAC drops below 0.02 or at 6pm. You will 
be provided with a ride home.
Interaction of alcohol and mavoglurant: There are no data currently available on the interaction of alcohol 
with mavoglurant. We are studying this interaction in the current study. 
Risks associated with urine collections: Screening urine collections are performed primarily as safeguards to 
subjects and should add no risks other than those normally associated with these procedures. 
Risks associated with rating scales and questionnaires: These are all noninvasive and should add no risk. The 
major disadvantages are the time taken to complete them or possible discomfort in answering certain items. 
Risks Associated with Blood Drawing: Drawing blood is a safe and standard medical procedure. Sometimes a 
bruise will occur at the puncture site and rarely a blood clot or infection will occur in the vein. Certain 
individuals may feel light-headed during venipuncture. 
You will have approximately 3.4 tbsps. of blood drawn at the PE appointment to determine liver and
kidney functioning. We will draw approximately 4.8 tbsps. of blood during the first lab session and 5.8 tbsps. of 
blood at the second lab session for BALs and health profile and PK samples. The morning after lab session 2, 
3.4 tbsps. of blood is drawn. At the 1 week follow up 3.4 tbsps. will be drawn again for health profile. 
Therefore, the total amount of blood drawn during the study (20.8 tbsps.) is well within the HIC guidelines of 
30.5 tbsps. within 8 research weeks, and the blood loss poses minimal risk in healthy subjects. We will advise 
subjects against donating blood for 6 weeks following study participation.
   
Risks Associated with Electrocardiograms (EKG/ECGs): There is no pain or discomfort during an EKG/ECG; 
however, removing the pads may cause some irritation to the skin.
Risks Associated with Intravenous Access: Insertion of an intravenous catheter involves risk for hematoma at 
the site of the venous puncture. Very rarely, venous puncture can also result in a blood clot or infection.
Pregnant women: Since alcohol drinking is harmful to an unborn child, pregnant women may not participate in 
this study. As a result, the following precautions are necessary if you are female: 1) Repeated pregnancy test 
will be performed using a urine sample. A positive pregnancy test will result in your being excluded from the 
study, 2) you must agree to use a reliable method of birth control during the study and 3) if you are a nursing 
mother, you will be excluded from the study.
Benefits
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You will not directly benefit from participating in this study. You may benefit by receiving, at no charge, a 
thorough screening and diagnostic evaluation, the results of which may be shared with you and, if you wish, 
with your physicians.  This research will benefit scientific knowledge and may lead to the development of a 
potential therapy for alcoholism.
Economic Considerations
You will not be charged for any of the tests or procedures conducted to determine eligibility for the study.  
Payment for the remote intake interview will be $50. You will also receive an additional $65 for the physical 
examination/in-person intake and up to $20 for the MSDM task.  You will also receive $140 for participating in 
the 1st laboratory session and $200 for completing the 2nd laboratory session. The morning after lab session 2 
we’ll have you come in-person to Quest Diagnostics for blood and urine collection $25 payment. Additionally, 
you will receive $10 for calling in via video chat to take your study medication (7-10 days), for up to a total of 
$100. You will be paid $30 for completing the one-week follow-up appointment. 
Appointment  
e-gift card (or 
cash)
Cash
Check
Intake   
$50
Physical Exam and in-person intake                     
$65
MSDM Computer Task at In-Person Intake
Up to $20
Lab Session #1                 
$140
Medication ($10/day for 7-10 days)
$70- $100
Lab Session #2                    
$200
Morning after Lab Session 2 blood and urine 
collection
$25
1 Week Follow Up
$30
This a total of up to $50 e-gift card (or cash at in-person), up to $85 in cash and up to $495 in the form of a 
check which will be mailed to you within 3-5 weeks of study completion for a grand total of up to $630.  If you 
must drop out of the study, then you will be paid for the portions that you complete.
*If you are asked to come back in for a repeat lab appointment (blood work, or EKG/ECG), we will 
compensate you $25 in cash for your time.
According to the rules of the Internal Revenue Service (IRS), payments that are made to you because of your 
participation in a study may be considered taxable income.
Subject Obligation
We ask that you do not use any medicines except mavoglurant or participate in any other research study without 
discussing this with us first while you are in our study. Please let us know if you do use any other medications 
or drugs during this time since we may need to reschedule your study sessions. You could be dismissed from 
the study if you repeatedly do not show up or lie about your alcohol and drug use. We will be monitoring your 
urine periodically for use of other drugs and your breath to assess alcohol level.  
Treatment Alternatives/Alternatives
This is not a treatment study. If you are currently interested in changing your drinking behavior, we will provide 
you with a treatment referral and you will not be eligible to participate in this study.
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Confidentiality and Privacy
When you participate in a research study, your identity as a research participant—and all the identifiers that 
could lead to your identity will be held confidentially.  The investigator cannot be forced to release your 
identifiers to anyone outside of the research team if a Certificate of Confidentiality is issued.  Thus, to protect 
your sensitive information, we have  a Certificate of Confidentiality (CoC) from the National Institute on 
Alcohol Abuse and Alcoholism (NIAAA) which is part of the National Institutes of Health (NIH). 
The CoC protects the identity of individuals in a study and protects the investigators from being forced to tell 
people that are not connected with this study about your participation in this study, even under a subpoena. This 
protection, however, is not absolute.  The protection offered by the CoC does not stop us from voluntarily 
reporting information about suspected or known sexual, physical, or other abuse of a child or older person, or a 
subject’s threats of violence to self or others. If any member of the research team is given such information, he 
or she will make a report to the appropriate authorities. Individuals who participate as research subjects (i.e., 
about whom the investigator maintains identifying information) in the specified research project are protected 
permanently during any time the Certificate is in effect. Also, because this research is sponsored by NIAAA, 
staff from NIAAA and other DHHS agencies may review records that identify you but only for the purposes of 
audit for quality and accuracy or program evaluation. 
Even when a CoC is in place, you must still continue to actively protect your own privacy. If you voluntarily 
give your written consent to anyone to receive information about your participation in the research or freely 
volunteer information to anyone other than the study staff that you are a research participant in this study, then 
we may not use the CoC to withhold this information.
If you decide that you will be in this study, and you will be visiting the Connecticut Mental Health Center 
(CMHC) as part of your study procedures, some information about your participation in this research study 
will become part of your CMHC medical record that identifies you. If you do not already have a medical 
record at CMHC, one will be made for your visit. This chart will say you are/were a research participant and 
had an EKG and lab work at the CMHC.
As a participant in a clinical research study involving the Yale-New Haven Hospital (YNHH) Research Unit 
(HRU), it is important for you to know that if you do not already have a medical record at YNHH, one will be 
made for your admission.  In addition, you need to know that if you have ever been a patient at YNHH at any 
time, your previous medical records of other visits or admissions will become available to the researchers and to 
the staff of the HRU/CSRU when today’s information is added into the medical record.
Information about your study participation will be entered into your Electronic Medical Record (EMR). This 
information will only indicate that you’ve participated in a research study and will not give details of the type of 
study. Once placed in your EMR, this information is accessible to all of your providers who participate in the 
EMR system. Information within your EMR may also be shared with others who are appropriate to have access 
to your EMR (e.g. health insurance company, disability provider) including the study physicians and study 
psychologist which may check your medical history, to ensure eligibility and safety for your research 
participation.
Any identifiable information that is obtained in connection with this study will remain confidential and will be 
disclosed only with your permission. Examples of information that we are legally required to disclose include 
abuse of a child or elderly person, or certain reportable diseases. There are certain circumstances when medical 
records can be demanded without your written permission.  In some cases, medical records can be requested, for 
example, by an insurance company, the government, or an attorney representing another person. When the 
results of the research are published, or discussed in conferences, no information will be included that would 
reveal your identity unless your specific consent for this activity is obtained.  
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We understand that information about you obtained in connection with your health is personal, and we are 
committed to protecting the privacy of that information.  If you decide to be in this study, the researcher will get 
information that identifies you and your personal health information.  Documents that contain your name, such 
as this consent form signed by you, will be securely stored separately from your research data.  All research 
data will be de-identified at the earliest reasonable time after we receive it, meaning we will replace your 
identifying information with a code that does not directly identify you. The principal investigator will keep a 
link that identifies you to your coded information, and this link will be kept secure and available only to the PI 
or selected members of the research team. Any information that can identify you will remain confidential.  All 
identifiable data will be kept in a locked file cabinet, separate from your research data. The data will be kept in 
this anonymous form at least seven years after the end of the study and will be shredded.  
You should understand that there is a risk that you will be recognized by other patients or staff involved in the 
laboratory or hospital ward and it could be known that you are participating in this study. If you find this to be 
an unacceptable condition you should not sign this consent form.
You will be given and encouraged to carry a wallet card that identifies the research study by a designated 
number, states that you are taking either Mavoglurant or placebo, but does not identify you as a participant in 
alcohol research. This card provides the name and phone number of the main study doctor who can provide 
information to other doctors in the event of an emergency.  The card also instructs the emergency room, or 
other doctor treating you to provide information to the study doctor about your care.
The information about your health that will be collected in this study includes: 

Name

Address

Telephone number

Information from a brief psychiatric examination

Emergency contact information

Initial telephone screening information

Healthcare, Social Functioning, and Addiction Questionnaires/Forms

Medical and laboratory records of only those services provided in connection with this Study.  

Records about phone calls made as part of this research

Research study records about your study visits

Hepatitis infection

Other reportable infectious diseases

Physical exams, Laboratory, EKG, and other test results

Questionnaires

The diagnosis and treatment of a mental health condition

Use of illegal drugs or the study of illegal behavior

Records about any study drug you received
Information about you and your health which might identify you may be used by or given to: 

The U.S. Department of Health and Human Services (DHHS) agencies

The FDA

Yale New Haven Hospital

Masonicare, Church Street Research Unit

Representatives from Yale University, the Yale Human Research Protection Program and the Yale 
Human Investigation Committee (the committee that reviews, approves, and monitors research on 
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human subjects), who are responsible for ensuring research compliance.  These individuals are 
required to keep all information confidential. 

Those individuals at Yale who are responsible for the financial oversight of research including 
billings and payments

Those providers who are participants in the Electronic Medical Record (EMR) system.

The Principal Investigator, Suchitra Krishnan-Sarin, PhD and the Center Principal Investigator, John 
Krystal, MD.

The study sponsor or manufacturer of study drug

Health care providers who provide services to you in connection with this study.

Co-Investigators and other investigators 

Study Coordinator and Members of the Research Team 

Data and Safety Monitoring Boards

Novartis, the supplier of the study medication, will also have access to your data however, they will 
only have access to your data that is un-identifiable.  They will not have any of your 
personal/identifying information so there will be no way for them to link you to your data.  
Similarly, your de-identified data may also be provided to the FDA. 
By signing this form, you authorize the use and/or disclosure of the information described above for this 
research study. The purpose for the uses and disclosures you are authorizing is to ensure that the information 
relating to this research is available to all parties who may need it for research purposes. 
All health care providers subject to HIPAA (Health Insurance Portability and Accountability Act) are 
required to protect the privacy of your information.  The research staff at the Yale School of Medicine and 
Yale-New Haven Hospital and the Connecticut Mental Health Center and Masonicare are required to comply 
with HIPAA and to ensure the confidentiality of your information.  Some of the individuals or agencies listed 
above may not be subject to HIPAA and therefore may not be required to provide the same type of 
confidentiality protection. They could use or disclose your information in ways not mentioned in this form. 
However, to better protect your health information, agreements are in place with these individuals and/or 
companies that require that they keep your information confidential. 
You have the right to review and copy your health information in your medical record in accordance with 
institutional medical records policies.  However, by deciding to take part in a single or double blinded treatment 
study and sign this permission form, you will not be allowed to look at or copy your study related information 
until after the research is completed.  
This authorization to use and disclose your health information collected during your participation in this study 
will never expire.
Voluntary Participation and Withdrawal
Participating in this study is voluntary. You are free to choose not to take part in this study.   Refusing to 
participate will involve no penalty or loss of benefits to which you are otherwise entitled (such as your health 
care outside the study, the payment for your health care, and your health care benefits).  However, you will not 
be able to enroll in this research study and will not receive study procedures as a study participant if you do not 
allow use of your information as part of this study.
Withdrawing from the Study
If you do become a subject, you are free to stop and withdraw from this study at any time during its course.  If 
you should choose to end the experimental session after you have consumed alcohol, we would ask you to stay 
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in the laboratory until your breath alcohol level falls to below 0.02 in order to ensure your safety.  In addition, 
we may insist that you accept transportation to your home.
To withdraw from the study, you can call a member of the research team at any time and tell them that you no 
longer want to take part.  This will cancel any future appointments.  
Withdrawing from the study will involve no penalty or loss of benefits to which you are otherwise entitled.  It 
will not harm your relationship with your own doctors or with Yale-New Haven Hospital, or the Connecticut 
Mental Health Center.  
Withdrawing Your Authorization to Use and Disclose Your Health Information
You may withdraw or take away your permission to use and disclose your health information at any time. You 
may withdraw your permission by telling the study staff or by writing to the study doctor, Dr. Krishnan-Sarin, 
Yale University, 34 Park Street, Ste S-208, New Haven, CT  06519.
If you withdraw your permission, you will not be able to stay in this study.
When you withdraw your permission, no new health information identifying you will be gathered after that 
date.  Information that has already been gathered may still be used and given to others until the end of the 
research study, as necessary to ensure the integrity of the study and/or study oversight.  
If the Principal Investigator decides to discontinue your participation in the research study, you will receive 
payment for all completed appointments.
In Case of Injury
If you are injured while on study, seek treatment and contact the study doctor as soon as you are able Dr. Julia 
Shi (203) 781-4640 or the Principal Investigator: Suchitra Krishnan-Sarin, PhD (203) 974-7595.  
Yale School of Medicine, Yale-New Haven Hospital, the Connecticut Mental Health Center, Masonicare 
Church Street Research Unit, and Novartis do not provide financial assistance for injury, medical or other costs 
and will not pay for lost wages or losses or for medical expenses that have been covered by medical or hospital 
insurance or by third party or governmental programs providing such coverage. You do not give up any legal 
rights by signing this form and may have other legal options.
If you are injured as a result of your participation in this study, treatment will be provided.  You or your 
insurance carrier will be expected to pay the costs of this treatment.  
Data Archive:
Data from this study will be submitted to the National Institute of Mental Health Data Archive (NDA) at the 
National Institutes of Health (NIH). NDA is a large database where deidentified study data from many NIH 
studies are stored and managed. Sharing your deidentified study data helps researchers learn new and important 
things about brain science more quickly than before.
Deidentified study data means that all personal information about you (such as name, address, birthdate and 
phone number) is removed and replaced with a code number. The study researchers will have to collect your 
personal information from you in order to make that code number. The code number cannot be used to identify 
you. The study researchers will never send your personal information to NDA. 
         
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It is possible that you will participate in more than one study that sends data to NDA. NDA can connect your 
data from different studies by matching the code number on your deidentified data from each study. This data 
matching helps researchers who use NDA data to count you only one time. It also helps researchers who use 
NDA to better understand your health and behavior without knowing who you are.
                                                             
During and after the study, the study researchers will send deidentified study data about your health and 
behavior to the NDA. Other researchers across the world can then request your deidentified study data for 
different research projects. Every researcher (and the institution to which they belong) who requests your 
deidentified study data must promise to keep your data safe and promise not to try to learn your identity. 
Experts at the NIH who know how to keep your data safe will review each request carefully to reduce risks to 
your privacy. Sharing your study data does have some risks, although these risks are rare. Your study data could 
be accidentally shared with an unauthorized person who may attempt to learn your identity. The study 
researchers will make every attempt to protect your identity.
You may not benefit directly from allowing your study data to be shared with NDA. The study data provided to 
NDA may help researchers around the world learn more about brain science and how to help others who have 
problems with brain science. NIMH will also report to Congress and on its website about the different studies 
using NDA data. You will not be contacted directly about the study data you contributed to NDA. 
You may decide now or later that you do not want your study data to be added to NDA. You can still participate 
in this research study even if you decide that you do not want your data to be added to NDA. If you know now 
that you do not want your data in NDA, please tell the study researcher before leaving the clinic today. If you 
decide any time after today that you do not want your data to be added to NDA, call or email the study staff 
who conducted this study, and they will tell NDA to stop sharing your study data. Once your data is part of 
NDA, the study researchers cannot take back the study data that was shared before they were notified that you 
changed your mind. If you would like more information about NDA, it is available on-line at http://nda.nih.gov.
Questions
We have used some technical terms in this form.  Please feel free to ask about anything you don't understand 
and to consider this research and the consent form carefully – as long as you feel is necessary – before you 
decide.
Authorization and Permission
I have read (or someone has read to me) this form and have decided to participate in the project described 
above.  Its general purposes, the particulars of my involvement and possible hazards and inconveniences have 
been explained to my satisfaction.  My signature also indicates that I have received a copy of this consent form.
By signing this form, I give permission to the researchers to use [and give out] information about me for the 
purposes described in this form.  By refusing to give permission, I understand that I will not be able to be in this 
research. 
Name of Subject: _____________________________
                        
Signature: ___________________________________
Date: ______________________________________
___________________________________________
___________________
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Signature of Principal Investigator
Date
   
                                    or
___________________________________________
___________________
Signature of Person Obtaining Consent
Date
If you have further questions about this project or if you have a research-related problem, you may contact the 
Principal Investigator, Suchitra Krishnan-Sarin, Ph.D. at 203-974-7595 or the study physician, Julia Shi, M.D. 
at (203)781-4640. If you would like to talk with someone other than the researchers to discuss problems, 
concerns, and questions you may have concerning this research, or to discuss your rights as a research subject, 
you may contact the Yale Human Investigation Committee at 203-785-4688. 
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