Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CHI-915 in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
This is a two-phase, randomized, double-blind, placebo-controlled, within-participant crossover study to assess the safety, tolerability, PK, and PD of five oral doses of CHI-915 versus placebo in healthy adult participants ages 18-55 years.

Official Title
-----------------
A Two-Phase, Randomized, Double-Blind, PlaceboControlled Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CHI-915 in Healthy Participants

Conditions
-----------------
Healthy Adults

Intervention / Treatment
-----------------
* Dietary Supplement: THCv


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is a healthy adult aged 18-55 years (inclusive) at the time of screening. Has a body mass index between 18 and 30 kg/m2. Is judged by the Investigator to be in generally good health at screening based on the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Laboratory results outside of the reference range deemed to be acceptable will be documented as not clinically significant at the discretion of the Investigator. For women of childbearing potential, has a negative serum pregnancy test (β-human chorionic gonadotropin [hCG]) at the Screening Visit and a negative urine pregnancy test at intake to the research facility. Must be adequately informed of the nature and risks of the study and give written informed consent prior to screening. Is, in the Investigator's opinion, reliable, able, and willing to comply with all protocol requirements and procedures (including scheduled visits). Exclusion Criteria: Women who are pregnant, lactating, breastfeeding, or planning a pregnancy. Women of childbearing potential, or men who are sexually active with a woman of childbearing potential, who are unwilling or unable to use an acceptable method of contraception (abstinence or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, vasectomy, or intrauterine device) from at least 21 days prior to the first dose of study medication until 28 days after the last dose of study medication. Participants with same sex partners or who maintain abstinence do not require contraception. Person has history of diagnosis related to hepatic function and/or significantly impaired hepatic function (alanine aminotransferase [ALT] >3x upper limit of normal [ULN] or total bilirubin [TBL] >2 x ULN) OR the ALT or aspartate aminotransferase (AST) >2 x ULN and TBL >2 x ULN (or international normalized ratio [INR] >1.5). Has a history of epilepsy. Has used tobacco/nicotine-containing products on more than 10 occasions within 30 days of dosing with study IP or during the study. Has used any prescription drugs or herbal supplements (except hormonal contraception) within 30 days prior to receiving the first dose of IP, unless approved by the Investigator and stable for at least 30 days prior to the first dose of IP through the final study visit. Use of any over-the-counter drugs, vitamins, or supplements within 24 hours prior to dosing with the IP. Has or has previously had a positive result for the presence of Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibodies (HCVAb), or human immunodeficiency virus (HIV) antibodies. Has a positive breath, urine, or serum test for ethanol or a positive urine screen for cocaine, THC, barbiturates, amphetamines, methamphetamines, benzodiazepines, methylenedioxymethamphetamine, phencyclidine, methadone, or opiates at the Screening Visit or prior to IP administration. Any clinically significant condition or abnormal finding at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with evaluation of the IP. Has a history of a known significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to cannabis, including phytocannabinoids and cannabinoid analogues, or excipients utilized within the IP. Has taken grapefruit products and/or Seville oranges within the 7 days prior to dosing with study medication or during the study. Is taking a prohibited medication or supplement including warfarin, clobazam, valproic acid, phenobarbital, mTOR inhibitors, oral tacrolimus, and St. John's Wort within 30 days prior to receiving the first dose of IP or during the study. Has used cannabis, synthetic cannabinoid, or cannabinoid analogues (e.g., dronabinol, nabilone), hemp products, synthetic cannabinoid receptor agonists (e.g., spice, K2), or any cannabidiol (CBD) or THC-containing product (e.g., Sativex, Epidiolex) within 4 weeks of the Screening Visit or during the study and has used cannabis on more than 25 occasions in the last 12 months. Meets criteria for past-year Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)-defined psychiatric disorder, or moderate to severe substance use disorder. Has a lifetime history of psychosis or schizophrenia or a first-degree relative experiencing psychosis or schizophrenia. Endorses current suicidal intent as indexed by endorsement of questions #4 or #5 on the Columbia-Suicide Severity Rating Scale (C-SSRS). Has suspected or confirmed cardiovascular disease. Has participated in any investigational product or device study within 30 days prior to receiving the first dose of IP or is scheduled to participate in another investigational product or device study during the course of this study. Demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The is a two-phase, within participant crossover study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group 1: Placebo<br>Single oral administration of 4 ml of Placebo MCT oil | Dietary Supplement: THCv<br>* THCv in MCT oil<br>|
| Active Comparator: Group 2: 12.5 mg THCv (CHI-915)<br>Single oral administration of 12.5 mg THCv in MCT oil | Dietary Supplement: THCv<br>* THCv in MCT oil<br>|
| Active Comparator: Group 3: 25 mg THCv (CHI-915)<br>Single oral administration of 25 mg THCv in MCT oil | Dietary Supplement: THCv<br>* THCv in MCT oil<br>|
| Active Comparator: Group 4: 50 mg THCv (CHI-915)<br>Single oral administration of 50 mg THCv in MCT oil | Dietary Supplement: THCv<br>* THCv in MCT oil<br>|
| Active Comparator: Group 5: 100 mg THCv (CHI-915)<br>Single oral administration of 100 mg THCv in MCT oil | Dietary Supplement: THCv<br>* THCv in MCT oil<br>|
| Active Comparator: Group 6: 200 mg THCv (CHI-915)<br>Single oral administration of 200 mg THCv in MCT oil | Dietary Supplement: THCv<br>* THCv in MCT oil<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, type and severity of AEs/SAEs | Incidence, type and severity of AEs/SAEs | Day 1 | 
| Incidence, type and severity of AEs/SAEs | Incidence, type and severity of AEs/SAEs | Day 8 | 
| Incidence, type and severity of AEs/SAEs | Incidence, type and severity of AEs/SAEs | Day 15 | 
| Incidence, type and severity of AEs/SAEs | Incidence, type and severity of AEs/SAEs | Day 22 | 
| Incidence, type and severity of AEs/SAEs | Incidence, type and severity of AEs/SAEs | Day 29 | 
| Incidence, type and severity of AEs/SAEs | Incidence, type and severity of AEs/SAEs | Day 36 | 
| Change in blood pressure | Change in systolic and diastolic blood pressure measured in mmHg | Day 1 | 
| Change in heart rate | Change in heart rate measured in beats per minute | Day 1 | 
| Change in respiratory rate | Change in respiratory rate measured in breaths per minute | Day 1 | 
| Change in body temperature | Change in body temperature measured in degrees Celsius | Day 1 | 
| Change in blood pressure | Change in systolic and diastolic blood pressure measured in mmHg | Day 8 | 
| Change in heart rate | Change in heart rate measured in beats per minute | Day 8 | 
| Change in respiratory rate | Change in respiratory rate measured in breaths per minute | Day 8 | 
| Change in body temperature | Change in body temperature measured in degrees Celsius | Day 8 | 
| Change in blood pressure | Change in systolic and diastolic blood pressure measured in mmHg | Day 15 | 
| Change in respiratory rate | Change in respiratory rate measured in breaths per minute | Day 15 | 
| Change in heart rate | Change in heart rate measured in beats per minute | Day 15 | 
| Change in body temperature | Change in body temperature measured in degrees Celsius | Day 15 | 
| Change in blood pressure | Change in systolic and diastolic blood pressure measured in mmHg | Day 22 | 
| Change in respiratory rate | Change in respiratory rate measured in breaths per minute | Day 22 | 
| Change in heart rate | Change in heart rate measured in beats per minute | Day 22 | 
| Change in body temperature | Change in body temperature measured in degrees Celsius | Day 22 | 
| Change in blood pressure | Change in systolic and diastolic blood pressure measured in mmHg | Day 29 | 
| Change in heart rate | Change in heart rate measured in beats per minute | Day 29 | 
| Change in respiratory rate | Change in respiratory rate measured in breaths per minute | Day 29 | 
| Change in body temperature | Change in body temperature measured in degrees Celsius | Day 29 | 
| Change in blood pressure | Change in systolic and diastolic blood pressure measured in mmHg | Day 36 | 
| Change in heart rate | Change in heart rate measured in beats per minute | Day 36 | 
| Change in respiratory rate | Change in respiratory rate measured in breaths per minute | Day 36 | 
| Change in body temperature | Change in body temperature measured in degrees Celsius | Day 36 | 
| Change in ECG results | Change in ECG results. Results summarized as Normal, Abnormal not clinically significant, and Abnormal clinically significant | Day 1 | 
| Change in ECG results | Change in ECG results. Results summarized as Normal, Abnormal not clinically significant, and Abnormal clinically significant | Day 8 | 
| Change in ECG results | Change in ECG results. Results summarized as Normal, Abnormal not clinically significant, and Abnormal clinically significant | Day 15 | 
| Change in ECG results | Change in ECG results. Results summarized as Normal, Abnormal not clinically significant, and Abnormal clinically significant | Day 22 | 
| Change in ECG results | Change in ECG results. Results summarized as Normal, Abnormal not clinically significant, and Abnormal clinically significant | Day 29 | 
| Change in ECG results | Change in ECG results. Results summarized as Normal, Abnormal not clinically significant, and Abnormal clinically significant | Day 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum effect for the item energetic on the DEQ | Maximum effect for the item energetic on the Drug Effects Questionnaire. Scale from 0-100 where higher scores indicate more energetic | Day 1 | 
| Maximum effect for the item energetic on the DEQ | Maximum effect for the item energetic on the Drug Effects Questionnaire. Scale from 0-100 where higher scores indicate more energetic | Day 8 | 
| Maximum effect for the item energetic on the DEQ | Maximum effect for the item energetic on the Drug Effects Questionnaire. Scale from 0-100 where higher scores indicate more energetic | Day 15 | 
| Maximum effect for the item energetic on the DEQ | Maximum effect for the item energetic on the Drug Effects Questionnaire. Scale from 0-100 where higher scores indicate more energetic | Day 22 | 
| Maximum effect for the item energetic on the DEQ | Maximum effect for the item energetic on the Drug Effects Questionnaire. Scale from 0-100 where higher scores indicate more energetic | Day 29 | 
| Maximum effect for the item energetic on the DEQ | Maximum effect for the item energetic on the Drug Effects Questionnaire. Scale from 0-100 where higher scores indicate more energetic | Day 36 | 
| Sustained attention - maximum total time on the DVT | Sustained attention - maximum total time on the DVT | Day 1 | 
| Sustained attention - maximum total time on the DVT | Sustained attention - maximum total time on the DVT | Day 8 | 
| Sustained attention - maximum total time on the DVT | Sustained attention - maximum total time on the DVT | Day 15 | 
| Sustained attention - maximum total time on the DVT | Sustained attention - maximum total time on the DVT | Day 22 | 
| Sustained attention - maximum total time on the DVT | Sustained attention - maximum total time on the DVT | Day 29 | 
| Sustained attention - maximum total time on the DVT | Sustained attention - maximum total time on the DVT | Day 36 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by maximum observed plasma concentration | Day 1 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by maximum observed plasma concentration | Day 8 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by maximum observed plasma concentration | Day 15 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by maximum observed plasma concentration | Day 22 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by maximum observed plasma concentration | Day 29 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by maximum observed plasma concentration | Day 36 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by time to maximum observed plasma concentration | Day 1 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by time to maximum observed plasma concentration | Day 8 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by time to maximum observed plasma concentration | Day 15 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by time to maximum observed plasma concentration | Day 22 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by time to maximum observed plasma concentration | Day 29 | 
| Pharmacokinetic profile of THCv | Pharmacokinetic profile of THCv measured by time to maximum observed plasma concentration | Day 36 |