An Study to Evaluate the Effects of Fluconazole on the Pharmacokinetics (PK) of Sativex® in Healthy Subjects With Cannabis Experience.

NCT02325011 | Completed Phase 1

• 2 other identifiers: GWCP14272014-003105-16
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to evaluate the effect of fluconazole on the pharmacokinetic (PK) profile of a single oromucosal dose of Sativex® (i.e. how the body absorbs, distributes, metabolises and excretes the drug) in healthy subjects with a history of cannabis use. The primary clinical hypothesis is that no drug-drug interaction between Sativex® and fluconazole will be detected as effects on PK parameters of Sativex®, when both are administered to healthy human volunteers who have experience using cannabis. The study additionally aims to evaluate the safety and tolerability of an oromucosal dose of Sativex® in subjects when given concurrently with fluconazole.

Conditions

Healthy Subjects

Keywords

Sativex; GW-1000-02; Nabiximols; Fluconazole; Pharmacokinetics; Drug-drug interaction

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetic parameters of Δ9 Tetrahydrocannabinol (THC): Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for THC: * Mean maximum (peak) plasma concentration of the drug (Cmax) * Mean area under the concentration-time curve calculated to the last observable concentration at time t (AUC(0-t)) * Mean area under the concentration-time curve from time zero to infinity (AUC(0-∞))

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• Pharmacokinetic parameters of 11-hydroxy-THC (11-OH-THC): Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for 11-OH-THC: * Mean Cmax * Mean AUC(0-t) * Mean AUC(0-∞)

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• Pharmacokinetic parameters of Cannabidiol (CBD): Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for CBD: * Mean Cmax * Mean AUC(0-t) * Mean AUC(0-∞)

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• Pharmacokinetic parameters of 7-hydroxy-CBD (7-OH-CBD): Cmax, AUC(0-t) and AUC(0-∞)

  The following are presented for 7-OH-CBD: * Mean Cmax * Mean AUC(0-t) * Mean AUC(0-∞)

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

Secondary Outcomes (9)

• Pharmacokinetic parameters of THC: t(1/2), tmax and CL/F

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• Pharmacokinetic parameters of 11-OH-THC: t(1/2) and tmax

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• Pharmacokinetic parameters of CBD: t(1/2), tmax and CL/F

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• Pharmacokinetic parameters of 7-OH-CBD: t(1/2) and tmax

  Pre-dose (t=0) and up to 48 hours post-dose (for each of the four treatment periods)

• The incidence of adverse events as a measure of subject safety

  From screening to follow-up (a maximum of 61 days)

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

During each of the four Inpatient Periods (Visit 2 to Visit 5 inclusive), healthy subjects with a history of cannabis use will either receive a single dose of Sativex® alone (Treatment A) or a single-dose of Sativex coadministered with the interaction drug, fluconazole (Treatment B) on a repeated, cross-over basis. Subjects will be randomly assigned to one of two treatment sequences. Treatment sequence 1 is as follows; * Visit 2 (Treatment A) * Visit 3 (Treatment B) * Visit 4 (Treatment A) * Visit 5 (Treatment B) The crossover treatments will be separated by a washout period of at least 10 days, but no more than 12 days, between each Sativex® dose.

Drug: Sativex® (Treatment A); Drug: Sativex® and fluconazole concomitantly (Treatment B)

Treatment Sequence 2

EXPERIMENTAL

During each of the four Inpatient Periods (Visit 2 to Visit 5 inclusive), healthy subjects with a history of cannabis use will either receive a single dose of Sativex® alone (Treatment A) or a single-dose of Sativex coadministered with the interaction drug, fluconazole (Treatment B) on a repeated, cross-over basis. Subjects will be randomly assigned to one of two treatment sequences. Treatment sequence 2 is as follows; * Visit 2 (Treatment B) * Visit 3 (Treatment A) * Visit 4 (Treatment B) * Visit 5 (Treatment A) The crossover treatments will be separated by a washout period of at least 10 days, but no more than 12 days, between each Sativex® dose.

Drug: Sativex® (Treatment A); Drug: Sativex® and fluconazole concomitantly (Treatment B)

Interventions

Sativex® (Treatment A) DRUG

Each 100 uL actuation (spray) of Sativex contains 27 mg/mL THC and 25 mg/mL CBD plus peppermint flavouring. The study dosage of 10.8 mg THC and 10 mg CBD is delivered as four sprays to the oral mucosa.

Also known as: Nabiximols, GW-1000-02, THC/CBD spray

Treatment Sequence 1; Treatment Sequence 2

Sativex® and fluconazole concomitantly (Treatment B) DRUG

Each 100 uL actuation (spray) of Sativex contains 27 mg/mL THC and 25 mg/mL CBD plus peppermint flavouring. The study dosage of 10.8 mg THC and 10 mg CBD is delivered as four sprays to the oral mucosa. Fluconazole 200 mg twice daily (BID) for two days, will be administered at the following time points relative to the Day 1 Sativex dose: 1 hour pre-dose, and approximately 11, 24, and 36 hours post-dose.

Also known as: Nabiximols, GW-1000-02, THC/CBD spray

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

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

You may qualify if:

• Willing and able to give written informed consent for participation in the study.
• Healthy, male or female, between 18 and 45 years of age (inclusive).
• Previous experience with cannabis; "cannabis experience" is defined as use of cannabis in the past, but not within 12 months prior to entry into the study.
• Able (in the investigator's opinion) and willing to comply with all study requirements.
• Willing and able to communicate with the investigator.
• Vital signs at screening (after five minutes resting measured in the supine position) within the following ranges:
• Body temperature between 35.0 to 37.5 °C
• Systolic blood pressure, 90 to 150 mmHg\*
• Diastolic blood pressure, 60 to 90 mmHg\*
• Pulse rate, 40 to 99 beats per minute\*. (\*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).
• Body mass index (BMI) between 18-30 kg/m2 (both inclusive) as calculated by the following BMI formula: Weight (kg) ÷ \[Height (m)\]2
• Willing for his or her name to be reported to the responsible authorities for participation in this study, as applicable in individual countries.
• Willing to allow his or her primary care practitioner and consultant to be notified of participation in the study.

You may not qualify if:

• The subject may not enter the study if ANY of the following apply:
• Donation or loss of 400 mL or more of blood within eight weeks prior to first dosing (Visit 2) and unwilling to abstain from donation of blood during the study.
• Significant concomitant illness within the two weeks prior to first dosing (Visit 2).
• At risk for requiring hospital admission or extended hospital stay during the study or any scheduled elective hospitalization during the planned study duration.
• Has any surgical or medical condition, significant disease or disorder or any finding on physical examination and/or oral examination which might significantly alter the absorption, distribution, metabolism or excretion of drugs or that, in the opinion of the investigator, may put the subject at risk, influence the result of the study, or the subjects' ability to participate in the study.
• Clinical evidence of acute or chronic liver disease or liver injury as indicated by clinically significant abnormal liver function tests such as aspartate aminotransferase, alanine aminotransferase, gamma glutamyl-transpeptidase, alkaline phosphatase, (any ≥2.5 upper limit of normal \[ULN\]) or serum bilirubin (≥1.5 ULN) unless there is another more likely explanation (eg, Gilbert's syndrome).
• Significant renal disease or significantly impaired renal function with an estimated creatinine clearance below 50 mL/min.
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, Sativex.
• Have a history of known hypersensitivity or idiosyncratic reaction to fluconazole, its excipients, or related compounds.
• Positive result for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCAb), or HIV I or II antibodies.
• Currently using or has used cannabis and/or cannabinoid based medications (eg, Marinol®, Nabilone®, Cannador®) or Acomplia (rimonabant) or taranabant within 12 months prior to first dosing (Visit 2) and is unwilling to abstain for the duration of the study.
• Currently using or has used an illicit drug or non prescribed use of any prescription drug within 12 months prior to first dosing (Visit 2) and is unwilling to abstain for the duration of the study.
• Any known or suspected history of a substance abuse/dependence disorder within the 12 months prior to first dosing (Visit 2).
• Has a positive urine drug (including THC) or alcohol result at screening or on Day -1 of Visit 2.
• Current heavy alcohol consumption (more than 60 g of pure alcohol per day for men, and more than 40 g of pure alcohol per day for women).

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

MeSH Terms

Conditions

Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Design

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

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 24, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

US (1)