Comparison of Safety, Tolerability and Pharmacokinetics of Medical Grade Cannabis (MGC) Orally Disintegrating Tablets With Buccal Sativex®, in Healthy Adult Volunteers

NCT03936907 | Completed Phase 1

• 2 other identifiers: OWC-ODP1220185282
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a preliminary study designed to assess the safety and properties of a new oral formulation containing the two most common cannabinoids used for medicinal purposes - Tetrahydrocannabinol (THC) and Cannabidiol (CBD). The formulation is designed to disintegrate sublingually in order to enhance absorption of these ingredients by circumventing first-pass metabolism by the liver (and probably also by the intestinal mucosal cells) as well as gastric acid degradation, thus allowing a rapid onset and more intensive pharmacological effect.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (6)

• Pharmacokinetic parameter- Tmax determined from plasma concentrations of THC, 11-hydroxy-THC and CBD.

  he amount of time requires for THC, 11-hydroxy-THC and CBD to reach to maximum concentration in serum

  24 hours post dosing

• Pharmacokinetic parameter -Cmax determined from plasma concentrations of THC, 11-hydroxy-THC and CBD.

  Mean highest observed plasma concentration of THC, 11-hydroxy-THC and CBD after dosing.

  24 hours post dosing

• Pharmacokinetic parameter- AUC0-t (area under the plasma concentration-time curve) determined from plasma concentrations of THC, 11-hydroxy-THC and CBD.

  24 hours post dosing

• Pharmacokinetic parameter- T½ determined from plasma concentrations of THC, 11-hydroxy-THC and CBD.

  The time required for the concentration of THC, 11-hydroxy-THC and CBD to reach half of its original value

  24 hours post dosing

• Pharmacokinetic parameter- kel determined from plasma concentrations of THC, 11-hydroxy-THC and CBD.

  Elimination rate constant K - The rate at which THC, 11-hydroxy-THC and CBD are removed from the body determined by their plasma concentration.

  24 hours post dosing

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerabilityof MGC-ODTand Sativex® ]

  Safety

  2 weeks post dosing

Study Arms (2)

Orally Disintegrating MGC-ODT Tablet

EXPERIMENTAL

Administration of a single tablet of Medical Grade Cannabis - Orally Disintegrating Tablet (MGC-ODT) containing 5mg THC and 5 mg CBD

Drug: OWCP Orally Disintegrating Tablet

Sativex®

ACTIVE COMPARATOR

Sativex® spray X 2 actuations (1 under the tongue and 1 inside the cheek administered within 2 min) - Reference Product \[Each 100 μL spray contains 2.7 mg THC and 2.5 mg CBD, total per administration: 5.4 mg THC and 5.0 mg CBD\]

Drug: Sativex

Interventions

OWCP Orally Disintegrating Tablet DRUG

Medical Grade Cannabis - Orally Disintegrating Tablet (MGC-ODT) containing 5 mg THC and 5 mg CBD

Orally Disintegrating MGC-ODT Tablet

Sativex DRUG

Sativex® Oromucosal Spray

Sativex®

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who provide written informed consent to participate in the study.
• Subjects who agree to have their name and details disclosed to the Israeli Ministry of Health and other responsible official authorities, as per the local legal requirement for participation in a THC study.
• Body Mass Index (BMI) ranging from 18 to \<30 kg/m2.
• Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs, ECG and a physical examination.
• No history of either recurrent or current buccal disorders (e.g. aphthae, xerostomia, infections).
• Supine blood pressure and heart rate within normal limits (systolic 90-140 mmHg; diastolic 50-90 mmHg, heart rate 45-100 beats per minute). No evidence of orthostatic hypotension.
• No clinically significant abnormalities in clinical laboratory parameters (hematology, blood chemistry, or urinalysis).
• Negative HIV 1/2, HBSAg, HCV serology tests at Screening.
• Subjects who agree to use an effective method of contraception during the course of the study. These include condom, having undergone a vasectomy or abstain from sexual intercourse.
• No known history of alcohol or drug abuse. Negative urinary screen for drugs of abuse as determined on the Screening visit and on admission before dosing.
• Willing to abstain from cannabis use 30 days before and throughout the study duration.
• Subjects must agree not to engage in potentially hazardous activities such as operating machinery, working at heights (e.g. maintenance and construction, climbing a ladder) throughout the study duration.
• Subjects must agree to abstain from driving from time of drug administration until 3 weeks after dosing.
• Subjects must agree to eat all the food and beverages provided during the study, and only these meals.
• Subjects must be able to understand the requirements of the study and must be willing to comply with the requirements of the study.

You may not qualify if:

• Known history of significant medical disorders including: cardiac, gastroenterological, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal (or other) that, as per the medical judgment of the principal investigator, could interfere with the execution and/or results of the study or contraindicates administration of the study medications.
• History of fainting or recurrent dizziness.
• History of epilepsy/seizures.
• History of any significant psychiatric disorder i.e., mania, depression, or schizophrenia.
• Any known or suspected history or family history of schizophrenia, or other psychotic illness, history of severe personality disorder or other severe significant psychiatric disorder other than reactive depression.
• Known hypersensitivity to cannabinoids (including cannabis extracts), excipients of tablet or of Sativex.
• Any history of cannabis dependence.
• Any history of adverse events associated with cannabis intoxication.
• A history of drug or alcohol abuse, or a history of regular alcohol consumption (by declaration) within 6 months of the study, defined as an average weekly intake of \>14 drinks. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Positive urine drug of abuse test on Screening and on admission to the CRC before dosing.
• A positive alcohol breath test on admission to the CRC before dosing.
• History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis).
• Any clinically significant abnormality upon physical examination or in the clinical laboratory tests at the Screening visit.
• Liver disease or liver injury manifested by clinically significant abnormal liver function tests
• Subjects receiving concomitant antipsychotic, sedative, hypnotic or other psychoactive drugs.

Sponsors & Collaborators

• One World Cannabis Ltd.: lead

Study Sites (1)

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel (isr), 6423906, Israel

Location

MeSH Terms

Interventions

nabiximols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequence ABBA

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: May 3, 2019
• Study Start: April 15, 2019
• Primary Completion: July 18, 2019
• Study Completion: July 18, 2019
• Last Updated: July 24, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)