5-Way Crossover Study to Compare the Safety, Tolerability and Pharmacokinetics of New Oral Cannabinoid Formulations Administered as Single Doses, With Buccal Sativex®, in Healthy Volunteers

NCT03201835 | Completed Phase 1

• 1 other identifier: CS-PYL-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study was to evaluate the safety and tolerability of novel oral capsules containing THC and/or CBD, following a single administration to healthy volunteers. The secondary objective of the study was to compare the pharmacokinetic profiles of THC, THC metabolite 11-hydroxy-THC and/or CBD following a single administration of the investigational oral formulations with Sativex® Oromucosal Spray.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Frequency, severity, and duration of adverse events (AEs), including clinically significant laboratory abnormalities after administration of the study drugs

  To evaluate the safety and tolerability of novel oral capsules containing THC and/or CBD, following a single administration to healthy volunteers. By evaluating frequency, severity, and duration of adverse events (AEs), including clinically significant laboratory abnormalities after administration of the study drugs

  during 8 weeks from screening

Secondary Outcomes (5)

• Calculating pharmacokinetics Tmax

  0-24 hours for each treatmet arm

• Calculating pharmacokinetics Cmax

  0-24 hours for each treatmet arm

• Calculating pharmacokinetics AUCT

  0-24 hours for each treatmet arm

• Calculating pharmacokinetics AUCInf

  0-24 hours for each treatmet arm

• Calculating pharmacokinetics T½.

  0-24 hours for each treatmet arm

Study Arms (5)

PNL-THC:CBD soft gelatin capsule

EXPERIMENTAL

3 soft capsules, containing a total of 10.8 mg THC and 10 mg CBD (Each capsule contains 3.6 mg THC and 3.3 mg CBD)

Drug: PNL-THC:CBD soft gelatin capsule

P-PNL-THC:CBD soft gelatin capsule

EXPERIMENTAL

2 soft capsules containing a total of 7.2 mg THC, 6.7 mg CBD and 20 mg piperine (Each capsule contains 3.6 mg THC, 3.3 mg CBD and 10 mg piperine)

Drug: P-PNL-THC:CBD soft gelatin capsule

CBD hard capsule dose 1

EXPERIMENTAL

1 hard capsule containing 10 mg CBD

Drug: CBD hard capsule dose 1

CBD hard capsule dose 2

EXPERIMENTAL

1 hard capsule containing 100 mg CBD

Drug: CBD hard capsule dose 2

Sativex®

ACTIVE COMPARATOR

spray X 4 actuations, Each 100 μL spray contains 2.7 mg THC and 2.5 mg CBD, total per administration: 10.8 mg THC and 10 mg CBD

Drug: Sativex

Interventions

PNL-THC:CBD soft gelatin capsule DRUG

3 soft capsules, containing a total of 10.8 mg THC and 10 mg CBD (Each capsule contains 3.6 mg THC and 3.3 mg CBD)

PNL-THC:CBD soft gelatin capsule

Sativex DRUG

spray X 4 actuations

Sativex®

CBD hard capsule dose 1 DRUG

1 hard capsule containing 10 mg CBD

CBD hard capsule dose 1

P-PNL-THC:CBD soft gelatin capsule DRUG

2 soft capsules containing a total of 7.2 mg THC, 6.7 mg CBD and 20 mg piperine (Each capsule contains 3.6 mg THC, 3.3 mg CBD and 10 mg piperine)

P-PNL-THC:CBD soft gelatin capsule

CBD hard capsule dose 2 DRUG

1 hard capsule containing 100 mg CBD

CBD hard capsule dose 2

Eligibility Criteria

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

You may qualify if:

• Healthy men between 18 and 45 years (inclusive) of age.
• Subjects who provide written informed consent to participate in the study.
• Body Mass Index (BMI) 19 to \<30 kg/m2 and weight ranging between 65-85 kg.
• Non-smoking and no use of any tobacco or nicotine products (by declaration) for a period of at least 6 months prior to screening visit
• Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
• Supine blood pressure and heart rate within normal limits (blood pressure: systolic 90-140 mmHg; diastolic 50-90 mmHg, heart rate 50- 100 beats per minute (bpm)) on Screening visit.
• Electrocardiogram (ECG) with no clinically significant abnormalities recorded at screening visit. Investigator assessment/discretion in cases of borderline results is allowed.
• Negative HIV, Hepatitis B and Hepatitis C serology tests at screening.
• No clinically significant abnormalities in hematology, blood chemistry, or urinalysis lab tests at screening.
• No known history of alcohol or drug abuse. Negative urinary screen for drugs of abuse determined on Screening visit and on admission before each dosing (urine THC will be measured only before first dosing).
• Subjects must be able to understand the requirements of the study and must be willing to comply with the requirements of the study.
• Subjects must agree to abstain from driving from first drug administration until 3 weeks after last dosing.
• Subject 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.
• Willing to abstain from cannabis use 30 days before and throughout the study duration.

You may not qualify if:

• Known hypersensitivity to cannabinoids (including cannabis extracts), excipients or capsules.
• Any history of adverse events associated with cannabis intoxication or dependence.
• Known/suspected history or family history of psychiatric disorders
• History of fainting or recurrent dizziness
• History of epilepsy/seizures.
• Documented history or ongoing symptoms of any gastrointestinal disorder involving motility, gastric acid or gastric emptying or malabsorption, including but not limited to, peptic ulcer disease, gastroesophageal reflux, dyspepsia, gastroparesis, chronic diarrhea, chronic constipation, gall bladder disease, pancreatitis, lactose intolerance and celiac disease.
• History of esophageal, gastric, biliary, or intestinal surgery (excluding herniotomy and appendectomy which are not related to gastrointestinal disorders).
• Known history of significant medical disorder, which in the investigator's judgment contraindicates administration of the study medications.
• Presence of mouth ulcerations or any abnormalities of the oral cavity.
• Any clinically significant abnormality upon physical examination or in the clinical laboratory tests at screening visit.
• Used cannabinoids or a cannabinoid-based medicine within 30 days prior to receiving study medication.
• Use of any prescription or over-the-counter (OTC) medications, vitamins and herbal or dietary supplements within 14 days prior to anticipated first dosing; subjects who had treatment with any known enzyme-altering agent (e.g. CYP450 inducers or inhibitors), within 30 days of first dosing. Paracetamol or for symptomatic relief of pain is allowed until 24 hours prior to first study drug administration.
• Known drug hypersensitivity or history of idiosyncratic reactions to any drug.
• Subjects with an abnormal diet, who had made substantial changes to eating habits within 30 days of the study,
• History of drug or alcohol abuse in the last two years.

Sponsors & Collaborators

• PhytoTech Therapeutics, Ltd.: lead

Study Sites (1)

Clinical Research Center (CRC)- Souraskey Medical center

Tel Aviv, Israel

Location

MeSH Terms

Interventions

nabiximols

Study Design

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

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 28, 2017
• Study Start: September 24, 2015
• Primary Completion: December 6, 2015
• Study Completion: June 6, 2016
• Last Updated: September 20, 2017

Record last verified: 2017-09

Locations

IL (1)