Bioequivalence Assessment of Oral Administration Vs. Oral Spray of a Cannabinoids (Tetrahydrocannabinol and Cannabidiol)

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

This project is intended to evaluate self-emulsifying drug delivery system termed Piperine-Pro-Nano-Lipospheres (P-PNL) for enhancing the oral bioavailability of tetrahydrocannabinol (THC) and cannabidiol (CBD).The oral bioavailability of these cannabinoids is hampered by extensive first pass metabolism, resulting in relative bioavailability of 6%.

The main goal of this study is to evaluate the bioequivalence of THC-CBD P-PNL product for oral administration to Sativex® buccal spray, as measured by AUC 0-24h, Tmax and Cmax.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Hadassah Medical Organization
• Treatments: Cannabidiol; Dronabinol; Nabiximols; Piperine

Criteria

Inclusion criteria:

• Men 18 through 45 years of age

• Body mass index in the range of: 25 through 30 kg/m2.

• Participants must be able to swallow and absorb oral medications.

• Normal Values Vital Sign Parameters as following: systolic blood pressure 90-139 mmHg, diastolic blood pressure 50-89 mmHg, pulse rate 45-100 bpm, body temperature 36.0-37.5º C.

• Subjects must be able to understand and comply with the requirements of the study (e.g. all medication, dietary, and alcohol restrictions).

• Subjects must provide written informed consent to participate in the study after reading the information and consent form, and after having an opportunity to discuss the study with the investigator.

• Subjects must complete the screening process within 4 weeks prior to the admission visit.

Exclusion criteria from study participation will include:

1. Previous participation in an investigational trial involving administration of any investigational compounds within two month prior to the current study.

2. Impaired glucose tolerance

3. Diabetes mellitus

4. Renal disease

5. Edema

6. Stroke or neurological disorder

7. Arthritis, joint or tendon abnormalities

8. History of asthma

9. Hepatic disorder

10. History of seizures

11. History of psychosis any addictive or other psychiatric disease disorder or a history of any illness that,might confound the results of the study or pose risk by participation in the study.

12. History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) 1 or 2.

13. History of cannabis intoxication or dependence.

14. Use of the forbidden drugs, substances or foods as follows:

14.1 Investigational product (THC or/and CBD ingestion or smoking) within one month preceding the study.

14.2 Prescription or non-prescription medication (including herbal, vitamins or dietary supplements) or vaccine within 14 days of the first day of study drug administration or within 5 half-lives before the first day of study drug administration.

Exceptions are locally acting medications (eg, topical creams), which are not allowed within 5 days of study drug administration, and the occasional use of acetaminophen (up to 3 g/day) and ibuprofen (up to 1200 mg/day).

14.3 Consumption of grapefruit, grapefruit juice, Seville oranges, pomelo containing products, within the 14 days prior to study and then throughout the study.

14.4 Excessive consumption of alcohol, defined as >3 drinks per day (beer, wine, or distilled spirits), or unwilling to comply with the restricted use of alcohol during the study (48 hours prior to admission and throughout the study)and history of alcoholism.

15. Previous surgery on the gastrointestinal tract [including removal of parts of stomach, bowel, liver, gall bladder, or pancreas] or stomach banding).

16. Exhausting physical exercise 48 hours prior to drug administration.

17. Excessive caffeine and xanthine containing foods and beverages (ie, equivalent to >4 cups brewed coffee per day) from 2 weeks prior to Day -1 and throughout the entire study.

18. Those who had donated >0.5 L blood within 30 days of study.

19. Abnormal heart function according to the following criteria:

20. The subject has a supine pulse rate outside of the range of 40 to 100 bpm (following at least a 10-minute rest) measured at screening or Day -1.

21. Supine blood pressure outside of the range of 90 to 139 mm Hg systolic or 50 to 89 mm Hg diastolic (following at least a 10 minute rest) measured at screening or Day-1. 11.

22. Clinically significant history of drug allergies (including cannabis extracts, propylene glycol, ethanol, or peppermint oil), drug hypersensitivity or history of idiosyncratic reactions to any drug.

23. Presence of mouth ulcerations or any damage of mouth and oral cavity.

24. History of abuse of any drug/chemical.

25. Inability to relate to and/or cooperate with the investigators.

26. A subject with any other condition, which, in the opinion of the investigator, makes the subject inappropriate for the study.