A Phase I Open Label Study to Assess PK and Safety of Plant Cannabis Extract

A Phase I Open Label Study to Assess the Single Dose Pharmacokinetics and Safety of Sublingual Administration of Tablets and Medicated Drops of Plant Cannabis Extract

This study is an open-label, single-dose, healthy volunteer phase 1 study after overnight fasting designed to study the safety and PK of medicated drops and tablet formulation for sublingual administration.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: A1; Drug: A2; Drug: A3; Drug: A4; Drug: A5; Drug: B1; Drug: B2; Drug: B3; Drug: B4

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Zefat, Israel, 13100
    • Ziv Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy, male or female, between 18 and 45 years of age (inclusive).
2. Body mass index (BMI) between 20-30 kg/m2 (both inclusive)
3. No recent cannabis usage within 30 days from screening
4. Normal rage hepatic functions
5. No electrolytes abnormalities

6. Vital signs at screening (after five minutes resting measured in the supine position) within the following ranges:

   1. Body temperature between 35.0 to 37.5 °C
   2. Systolic blood pressure, 90 to 150 mmHg*
   3. Diastolic blood pressure, 60 to 90 mmHg*
   4. Pulse rate, 50 to 90 beats per minute*.
   5. *Blood pressure and pulse rate will be taken again in a standing position. After two minutes standing, there shall be no more than a 20 mmHg drop in systolic or 10 mmHg drop in diastolic blood pressure, associated with clinical manifestation of postural hypotension).

Exclusion Criteria:

1. Blood donation within 90 days
2. History of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastroenterology, endocrine, immunology, dermatologic, neurologic or psychiatric disorders
3. Subjects with a history of alcohol, drug abuse, chronic cannabis use within 2 years of study
4. Pregnant women
5. Subjects who used any prescription or OTC medication in the past 14 days with the exception of paracetamol or ibuprofen.
6. Sexually active males whose partner is of childbearing potential who do not agree to practice two highly effective methods of birth control or remain abstinent during the study and for three months after the last dose of IMP. Sexually active females of childbearing potential who do not agree to practice two highly effective methods of birth control or remain abstinent during the study and for three months after the last dose of IMP
7. Pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
8. Subjects who had postural drop of > 20 mmHg in systolic blood pressure at screening
9. Patients with heart failure,
10. Subjects with a history of psychotic state in the past or anxiety disorder,
11. Subjects at age of less than 30 years with a history of psychiatric disease in a first-degree family member
12. Subjects with a history of addiction or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose; Single dose in fasted state of : A1, A2,A3, A4, A5, B1, B2, B3, B4	Drug: A1; Medical Cannabis oil diluted in Olive oil. CBD 36.6 mg, THC 1.8 mg (6 drops); Other Names: Celixir 20 T1/C20- CBD 20%, THC 1%; Drug: A2; Medical Cannabis oil diluted in Olive oil. CBD 0.6 mg, THC 3.1 mg (1 drop); Other Names: Telixir 10 T2/C10 - CBD 2%, THC 10%; Drug: A3; Medical Cannabis oil diluted in Olive oil. CBD 3.1 mg. THC 3.1 mg (1 drop); Other Names: Equatir 10 T10/C10 - CBD 10%, THC 10%; Drug: A4; Medical Cannabis (oil diluted in MCT oil). CBD 34.8 mg, THC 1.7 mg (6 drops); Other Names: C18T0.9 in MCT oil - CBD 18%, THC 0.9%; Drug: A5; Medical Cannabis oil (diluted in MCT oil). CBD 0.6 mg, THC 3.1 mg (1 drop); Other Names: T10/C2 - CBD 2%, THC 10%; Drug: B1; Sublingual tablets. CBD 40 mg, THC 2 mg (1 tablet); Other Names: Tablet: CBD 40 mg, THC 2 mg; Drug: B2; Sublingual tablets. CBD 30 mg, THC 5 mg (1 tablet); Other Names: Tablet: CBD 30 mg, THC 5 mg; Drug: B3; Sublingual tablets. CBD 40 mg (1 tablet); Other Names: Tablet: CBD 40 mg; Drug: B4; Sublingual tablets. CBD 40 mg (1 tablet); Other Names: Tablet: CBD 40 mg
Experimental: Cross-Over food effect; 2 doses: fasted and fed state with the same product: A1, A4, A5, B4	Drug: A1; Medical Cannabis oil diluted in Olive oil. CBD 36.6 mg, THC 1.8 mg (6 drops); Other Names: Celixir 20 T1/C20- CBD 20%, THC 1%; Drug: A4; Medical Cannabis (oil diluted in MCT oil). CBD 34.8 mg, THC 1.7 mg (6 drops); Other Names: C18T0.9 in MCT oil - CBD 18%, THC 0.9%; Drug: A5; Medical Cannabis oil (diluted in MCT oil). CBD 0.6 mg, THC 3.1 mg (1 drop); Other Names: T10/C2 - CBD 2%, THC 10%; Drug: B4; Sublingual tablets. CBD 40 mg (1 tablet); Other Names: Tablet: CBD 40 mg
Experimental: Cross-Over product comparison; 2 doses: in fasted state comparing A1 to A4	Drug: A1; Medical Cannabis oil diluted in Olive oil. CBD 36.6 mg, THC 1.8 mg (6 drops); Other Names: Celixir 20 T1/C20- CBD 20%, THC 1%; Drug: A4; Medical Cannabis (oil diluted in MCT oil). CBD 34.8 mg, THC 1.7 mg (6 drops); Other Names: C18T0.9 in MCT oil - CBD 18%, THC 0.9%
Experimental: Cross-over route of administration comparison; 2 doses: in fasted state comparing oral administration to sublingual administration of A4	Drug: A4; Medical Cannabis (oil diluted in MCT oil). CBD 34.8 mg, THC 1.7 mg (6 drops); Other Names: C18T0.9 in MCT oil - CBD 18%, THC 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic analysis of Cmax	0-12 hours post dose
Pharmacokinetic analysis of Tlag	0-12 hours post dose
Pharmacokinetic analysis of Tmax	0-12 hours post dose
Pharmacokinetic analysis of AUC(0-t)	0-12 hours post dose
Pharmacokinetic analysis of AUC(0-∞)	0-12 hours post dose
Pharmacokinetic analysis of %AUC extrapolated	0-12 hours post dose
Pharmacokinetic analysis of T1/2	0-12 hours post dose
Pharmacokinetic analysis of clearance from plasma (Cl/F)	0-12 hours post dose
Pharmacokinetic analysis of ratio of the Volume of distribution based on the terminal phase to the bioavailability (Vz/F)	0-12 hours post dose
Pharmacokinetic analysis of clearance from plasma dose normalized Cmax	0-12 hours post dose
Pharmacokinetic analysis of dose normalized AUC	0-12 hours post dose

Collaborators and Investigators

• Sponsor: Breath of Life International Pharma Ltd

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2019
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse
• Other Study ID Numbers: BOL-PK-ST-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No