Single and Multiple Dose Study of VER-01 in Healthy Volunteers

Study Overview
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Brief Summary
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Evaluation of pharmacokinetics, tolerability and safety of VER-01 in healthy volunteers

Detailed Description
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Determination of the single and multiple dose pharmacokinetic profile of VER-01 in healthy volunteers. Single dose: 6 subjects each will receive VER-01 corresponding to 2.5 mg (Group A), 5 mg (Group B), 10 mg (Group C) or 20 mg THC (Group D) in the morning. Multiple dose: 6 Subjects each receive VER-01 corresponding to 5 mg (Group E) or 10 mg (Group F) THC in the morning and in the evening on 4 consecutive days. A third group (Group G) receives VER-01 corresponding to 12.5 mg THC in the morning and 20 mg THC in the evening on 4 consecutive days.

Official Title
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Open-label Study to Evaluate the Pharmacokinetics and Safety of VER-01after Single and Multiple Administration of Different Doses to Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: VER-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male volunteers Age: 18-45 years BMI: 19-30 kg/m² Body weight ≥ 50 kg volunteers in good general condition based on medical history, physical examination, resting ECG and clinical laboratory tests Willingness of men to use a reliable method of contraception and not to donate sperm during and at least 3 months after the last intake of the study product Understanding of the German language, ability to give consent and compliance The subject has understood the instructions to avoid changes in lifestyle and eating habits Signed patient information and written informed consent form of the study participant Exclusion Criteria: Consumption of cannabis-based products within 30 days prior to study start Well-known strong adverse events in connection with cannabis consumption Known allergy to cannabis, sesame seeds, or derivative products alcohol/drug/medication abuse or physical dependence on opioids, barbiturates, amphetamines, cocaine or benzodiazepines within the last 10 years or current intake of methadone Positive drug test for illegal substances and/or alcohol test at time T0 Heavy smokers (>10 cigarettes/day) Heavy caffeine consumers (>450 mg caffeine/day equal to approx. 5-6 cups of filter coffee) Drastic change in diet within 30 days before study start Mental illness (psychoses, schizophrenia, bipolar disorder, severe depression, anxiety disorder, suicide) Mental illness (psychoses, schizophrenia, bipolar disorder, severe depression, anxiety disorder, suicide) in a first-degree relative (parents and children) subjects with orthostatic hypotension during screening (drop in systolic blood pressure by ≥20 mmHg after change of position) Cardiovascular event within the last 3 months, untreated hypertension, untreated hypothyroidism, surgery within the last 2 months cardiac insufficiency Subjects with a serious disease or disorder which, in the opinion of the investigator, does not allow safe participation in the study from a medical point of view Intake of prescription drugs within the last 14 days, over-the-counter test products within the last 7 days before the start of the study or during the study period Eating of grapefruit products is not allowed during the study and 10 days before the first intake of the study product Participation in another clinical trial in the period of 90 days before the start of the trial Existing desire to have children or planned sperm donation (within the duration of the study and 3 months after end of the study) Planned blood donation No ability to consent Subject is in a dependency/employment relationship with the sponsor or investigator or other persons who may be under pressure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VER-01 single dose (2.5 mg THC)<br>PK profile is investigated after oral intake of a single dose VER-01 corresponding to 2.5 mg THC (Group A). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|
| Experimental: VER-01 single dose (5 mg THC)<br>PK profile is investigated after oral intake of a single dose VER-01 corresponding to 5 mg THC (Group B). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|
| Experimental: VER-01 single dose (10 mg THC)<br>PK profile is investigated after oral intake of a single dose VER-01 corresponding to 10 mg THC (Group C). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|
| Experimental: VER-01 single dose (20 mg THC)<br>PK profile is investigated after oral intake of a single dose VER-01 corresponding to 20 mg THC (Group D). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|
| Experimental: VER-01 multiple dose (5 mg THC)<br>PK profile is investigated after oral intake of VER-01 corresponding to 5 mg THC in the morning and 5 mg THC in the evening on 4 consecutive days (Group E). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|
| Experimental: VER-01 multiple dose (10 mg THC)<br>PK profile is investigated after oral intake of VER-01 corresponding to 10 mg THC in the morning and 10 mg THC in the evening on 4 consecutive days (Group F). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|
| Experimental: VER-01 multiple dose (12.5 / 20 mg THC)<br>PK profile is investigated after oral intake of VER-01 corresponding to 12.5 mg THC in the morning and 20.5 mg THC in the evening on 4 consecutive days (Group F). | Drug: VER-01<br>* standardised cannabis extract (containing 21 mg THC per gram drug product)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC] - AUC 0-t | Analysis of the AUC 0-t (AUC from time 0 to 24 hours) of THC over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC] - AUC 0-∞ | Analysis of AUC 0-∞ (AUC from time 0 extrapolated to infinity) of THC over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC] - C max | Analysis of C max (maximum plasma concentration) of THC over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - AUC 0-t | Analysis of AUC 0-t (AUC from time 0 to 24 hours) of 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - AUC 0-∞ | Analysis of AUC 0-∞ (AUC from time 0 extrapolated to infinity) of 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - C max | Analysis of C max (maximum plasma concentration) of 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - λ z | Analysis of λ z (terminal elimination constant) of THC, 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - t 1/2 | Analysis of t 1/2 (elimination half-life) of THC, 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - T max | Analysis of T max (time to reach Cmax) of THC, 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - C L/F | Analysis of C L/F (plasma clearance) the pharmacokinetic profile of THC, 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 
| Pharmacokinetic profile of Δ9-tetrahydrocannabinol [THC], 11-Hydroxy-Δ9-tetrahydrocannabinol [11-OH-THC] and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol [THC-COOH] - V area/F | Analysis of V area/F (volume of distribution) of THC, 11-OH-THC and THC-COOH over a defined period of time. | Group A-D: Day 1; Group E-G: Day 1 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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THC, Tetrahydrocannabinol, Cannabis, Pharmacokinetics