A Randomized Controlled Test of the Effects of CHI-554 on Fear.

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled phase 2b clinical trial examining the effects of CHI-554 (CBD) on Fear (F-01)

Detailed Description
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This study will examine the potential of a novel formulation of hemp-derived CBD (CHI-554) to reduce fear elicited via a safe, well-established, controlled, laboratory-based carbon dioxide (CO2)-enriched air biological challenge that causes abrupt increases in bodily arousal.

Official Title
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A Randomized Controlled Test of the Effects of CHI-554 on Fear (F-01)

Conditions
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Anxiety, Fear, Panic

Intervention / Treatment
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* Drug: CHI-554


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Person is between 18 and 55-years-old (inclusive). Person has a BMI between 18 and 35 kg/m2 (inclusive). Person is willing and able to provide informed consent and attend a 3.5-hour, in-person session. Woman of childbearing potential must not be pregnant or currently breastfeeding. If person uses medication, the person has maintained a stable dose and regimen on existing medications for at least 30 days prior to participation in the study and throughout the study. Person agrees to abide by all study restrictions and comply with all study procedures. Exclusion Criteria: Person has a known history of significant allergic condition, significant hypersensitivity to the IP, or allergic reaction to cannabis, cannabinoid medications, hemp products, or excipients of the IP. Person has been exposed to any investigational drug or device < 30 days prior to screening or plans to take an investigational drug in the near future (within 30 days). Person has used cannabis, synthetic cannabinoid or cannabinoid analogue (e.g., dronabinol, nabilone), synthetic cannabinoid receptor agonist (e.g., spice, K2), or any CBD- or delta-9- tetrahydrocannabinol (THC)-containing product within 30 days of screening or during the study. Person is currently prescribed medications with likely THC- or CBD- interactions (e.g., warfarin, clobazam, valproic acid, phenobarbital, mechanistic target of rapamycin [mTOR] inhibitors, oral tacrolimus, St. John's wort; Epidiolex). Person is currently prescribed and using a medication used in the treatment of anxiety disorders (e.g., selective serotonin uptake inhibitors, venlafaxine, buspirone, benzodiazepines, hydroxyzine, tiagabine, gabapentin, valproate, lamotrigine, topiramate, beta blockers, clonidine, guanfacine, atypical antipsychotics); Person has a positive drug screen for THC, barbiturates, amphetamines, benzodiazepines, and/or opiates at baseline assessment. Person meets diagnostic criteria for a current DSM-5 diagnosis indexed via the MINI. Person meets criteria for a lifetime history of an unexpected or unprovoked panic attack indexed via the MINI. Person endorses current suicidal intent as indexed via the C-SSRS. Person reports a history of being diagnosed with a respiratory or lung disease (including asthma attacks), cardiac or pulmonary disease, epilepsy, narcolepsy, sleep apnea, anemia, or renal disease during a medical history interview. Person has participated in a study that used a CO2-enriched air procedure. Person has received formal training to tolerate elevated levels of CO2 or bodily arousal (such as free diver training or interoceptive exposure-based treatment). Any other clinically significant disease or disorder or abnormal findings during screening or the baseline assessment that, in the opinion of the investigator, may either put the person at risk because of participation in the study, may confound the results of the study, or affect the person's ability to participate in the study. Person has an acute or progressive disease that is likely to interfere with the objectives of the study, or the ability to adhere to protocol requirements. Woman of childbearing potential, unless she has not engaged in vaginal intercourse or she has used effective contraception when doing so (for example, oral contraception, double barrier, intra-uterine device) for at least 30 days prior to the study. Woman of childbearing potential, unless willing to ensure that she or her partner use effective contraception (for example, oral contraception, double barrier, intra-uterine device) during the study and for 30 days thereafter (however, a male condom should not be used in conjunction with a female condom). Man whose partner is of childbearing potential, unless willing to ensure that he or his partner use effective contraception (for example, oral contraception, double barrier, intra-uterine device) during the study and for 30 days thereafter (however, a male condom should not be used in conjunction with a female condom). Person has history of diagnosis related to hepatic function and/or significantly impaired hepatic function (alanine aminotransferase [ALT] >5 ´ upper limit of normal [ULN] or total bilirubin [TBL] >2 ´ ULN) OR the ALT or aspartate aminotransferase (AST) >3 ´ ULN and TBL >2 ´ ULN (or international normalized ratio [INR] >1.5). Person demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 2b, randomized, double-blind, placebo-controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>150 mg CBD | Drug: CHI-554<br>* hemp-derived CBD in MCT oil<br>|
| Experimental: Group 2<br>300 mg CBD | Drug: CHI-554<br>* hemp-derived CBD in MCT oil<br>|
| Experimental: Group 3<br>600 mg CBD | Drug: CHI-554<br>* hemp-derived CBD in MCT oil<br>|
| Placebo Comparator: Group 4<br>Placebo MCT oil | Drug: CHI-554<br>* hemp-derived CBD in MCT oil<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fear ratings | Mean mid-challenge fear ratings measured (via continuous transducer input with a range of 1 to 10, where higher ratings reflect more fear) during seconds 300-330 of the experimental procedure (seconds 150-180 of the biological challenge). | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC in mean fear ratings | Area under the curve with respect to increase (AUCI) in mean fear ratings (measured via continuous transducer input, with a range of 1 to 10, where higher ratings reflect more fear) sampled at baseline and during 30-second epochs each minute before, during, and after the biological challenge as calculated using the trapezoidal formula. | 1 day | 
| Self-reported anxiety | Self-reported anxiety (state form of the Spielberger State-Trait Anxiety Inventory (STAI), with a possible range of scores from 20 to80, where higher scores reflect greater anxiety) measured immediately prior to beginning the biological challenge. | 1 day | 
| AUC in state anxiety ratings | AUC-I in state anxiety ratings (VAS) across the experimental period as calculated using the trapezoidal formula. | 1 day | 
| Mean intensity using DSQ | mean intensity of physical attack symptoms, cognitive panic attack symptoms, and percentage of participants endorsing a panic attack. | 1 day |