A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study to Assess the Safety and Pharmacokinetics of CHI-936 in Healthy Participants

INTERVENTION: This is a Phase 1a, randomized, double‐blind, placebo‐controlled, multiple‐dose study to assess the safety, tolerability, and PK of CHI‐936 versus placebo in healthy male and female participants ages 18–55 years. The study will enroll 40 participants (8 participants per group; 4 active treatment groups and 1 placebo group). During the Treatment Period, participants will be randomized in a 1:1:1:1:1 ratio to 1 of 5 treatment groups: • Treatment A: 120 mg total CBD and 5.4 mg total THC daily (3 mL CHI‐936 and 15 mL placebo, twice daily) • Treatment B: 240 mg total CBD and 10.8 mg total THC daily (6 mL CHI‐936 and 12 mL placebo, twice daily) • Treatment C: 360 mg total CBD and 16.2 mg total THC daily (9 mL CHI‐936 and 9 mL placebo, twice daily) • Treatment D: 480 mg total CBD and 21.6 mg total THC daily (12 mL CHI‐936 and 6 mL placebo, twice daily) • Treatment E: Placebo (18 mL placebo, twice daily). Treatment will be administered every 12 hours orally. CHI‐936 is a cannabis oil that contains an approximate 20:1 ratio of CBD to THC (20 mg/mL CBD and < 1 mg/mL THC). The intervention (i.e. treatment with IMP) will be 7 days and will monitored and documented during inpatient stay. CONDITION: Alternative and Complementary Medicine ‐ Other alternative and complementary medicine Pain;Nausea;Muscle Spasticity;Epilepsy; ; Pain ; Nausea ; Muscle Spasticity ; Epilepsy PRIMARY OUTCOME: To evaluate the safety and tolerability of CHI‐936 administered twice daily for a total daily dose of 120 mg CBD and 5.4 mg THC, 240 mg CBD and 10.8 mg THC, 360 mg CBD and 16.2 mg THC, or 480 mg CBD and 21.6 mg THC.[For 7 consecutive days relative to placebo.; ; Patient safety will be monitored at all visits and during the inpatient Treatment Period using standard measures including physical examinations, vital sign assessments, 12 lead electrocardiogram (ECG), safety laboratory analyses, urinalysis, and adverse event (AE) monitoring. Additionally, the Columbia Suicide Severity Rating Scale (C‐SSRS) will be administered at screening, pre‐morning dose on Days 1 through 7, at Inpatient Discharge on Day 8, and at Visit 6 (Day 13). ] SECONDARY OUTCOME: To characterize and compare the PK of 7‐CBD‐COOH assessed in blood plasma and urine of 4 different daily doses of CHI‐936.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of 11‐OH‐THC assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of 6a‐OH‐CBD assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of 6ß‐OH‐CBD assessed in blood plasma and urine of 4 different daily doses of CHI‐936.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of 7‐OH‐CBD assessed in blood plasma and urine of 4 different daily doses of CHI‐936.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of CBC assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of CBD assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; ; PK parameters for CBD and metabolites will be calculated/derived from the data using a non‐compartmental analysis with WinNonlin. Actual sampling times will be used to estimate plasma PK parameters. Descriptive statistics (arithmetic mean, SD, median, minimum, maximum, coefficient of variation, and geometric mean) for the individual PK parameters and plasma concentration over time will be presented by treatment group and period. Differences in dose‐dependent PK parameters (Cmax, Cmin, Cav, and AUC) between Treatments A, B, C, and D will be compared using an ANOVA model or an appropriate non‐parametric approach. The pre‐dose Ctrough plasma levels across all the days of dosing will be compared statistically for assessment of the steady state at each dose regimen using a mixed effect ANOVA model. Attainment of the steady state will be concluded if the 90% CI for the geometric mean ratio of Days 5/6, 5/7, and 6/7 are completely within the acceptance range of 0.80–1.25.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of CBD‐Gluc assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of CBDV assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of CBG assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of CBN assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of THC assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of THC‐COOH assessed in blood plasma and urine of 4 different daily doses of CHI‐936.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; PK parameters for THC and metabolites will be calculated/derived from the data using a non‐compartmental analysis with WinNonlin. Actual sampling times will be used to estimate plasma PK parameters. Descriptive statistics (arithmetic mean, SD, median, minimum, maximum, coefficient of variation, and geometric mean) for the individual PK parameters and plasma concentration over time will be presented by treatment group and period. Differences in dose‐dependent PK parameters (Cmax, Cmin, Cav, and AUC) between Treatments A, B, C, and D will be compared using an ANOVA model or an appropriate non‐parametric approach. The pre‐dose Ctrough plasma levels across all the days of dosing will be compared statistically for assessment of the steady state at each dose regimen using a mixed effect ANOVA model. Attainment of the steady state will be concluded if the 90% CI for the geometric mean ratio of Days 5/6, 5/7, and 6/7 are completely within the acceptance range of 0.80–1.25.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of THC‐COOH‐Gluc assessed in blood plasma and urine of 4 different daily doses of CHI‐936.[Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of THC‐Gluc assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of THCV assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To characterize and compare the PK of THCV‐COOH assessed in blood plasma and urine of 4 different daily doses of CHI‐936. ; [Blood samples (4 mL per sample) for plasma PK measurements will be collected at the following time points: ; Day 1: Pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose ; Days 2–6: Pre‐morning dose ; Day 7: Pre‐morning dose and at 1, 2, 4, 6, 8, 12, and 16 hours after the morning dose ; Day 8: 24 and 32 hours after the Day 7 morning dose ; Day 9: 48 hours after the Day 7 morning dose ; Day 10: 72 hours after the Day 7 morning dose ; Day 11: 96 hours after the Day 7 morning dose ; Day 13: 144 hours after the Day 7 morning dose. ; ; Urine samples for urine PK measurements will be collected at the following time points: ; Days 1–6: Pre‐morning dose ; Day 7: Output (all samples provided) for the 00:00–12:00 and 12:00–24:00 intervals. ; ] To explore the subjective effects of CHI‐936 in healthy participants via the completion of a Drug Effects Questionnaire (DEQ).[The DEQ will be administered pre‐morning dose and at 1, 2, 4, 6, 8, and 12 hours after the morning dose on Days 1, 3, and 7] INCLUSION CRITERIA: 1. Is a healthy male or female adult aged 18–55 years at the time of screening. 2. Has a minimum of 2 lifetime exposures to THC‐containing cannabis products. 3. Has a body mass index between 18 and 30 kg/m2. 4. 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. 5. For women of childbearing potential, has a negative serum pregnancy test (ß‐human chorionic gonadotropin [hCG]) at the Screening Visit and a negative urine pregnancy test at intake to the inpatient research facility. 6. Agrees to abide by all study restrictions and comply with all study procedures. 7. Must be adequately informed of the nature and risks of the study and give written in