A Randomised, Open-label, Three-way Crossover Study to Assess the Pharmacokinetics and Safety of Single Doses of Four Sprays of Sativex® in a Range of Oral pH Environments in Healthy Subjects

NCT02240160 | Terminated Phase 1

• 2 other identifiers: GWCP101162013-004459-19
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the effect of oral pH on the pharmacokinetics (PK) of a single oromucosal dose of Sativex (four sprays containing 10.8 mg Δ9 tetrahydrocannabinol (THC) and 10 mg cannabidiol (CBD)) by comparing the PK profile of Sativex in healthy subjects. The primary clinical hypothesis is that there will be an effect of oral pH on the PK of Sativex when administered as a single oromucosal dose (four sprays).

Conditions

Healthy Volunteers

Keywords

Sativex; Pharmacokinetics; Oral pH

Outcome Measures

Primary Outcomes (2)

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

  Mean highest observed plasma concentration of the measured concentration-time profile (Cmax), area under the concentration-time curve from administration to the last sampling point (AUC(0-t)), and area under the concentration-time curve extrapolated to infinity (AUC(0-∞)) of THC are presented.

  0-24 hours post-dose

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

  Mean Cmax, AUC(0-t), and AUC(0-∞) of CBD are presented.

  0-24 hours post-dose

Secondary Outcomes (16)

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

  0-24 hours post-dose

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

  0-24 hours post-dose

• Pharmacokinetic parameters of 6-hydroxy-CBD (6-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)

  0-24 hours post-dose

• Pharmacokinetic parameters of THC: t½ and Tmax

  0-24 hours post-dose

• Pharmacokinetic parameters of 11-OH-CBD: t½ and Tmax

  0-24 hours post-dose

Study Arms (3)

Sativex: acidic oral pH

EXPERIMENTAL

Four sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with Coca-Cola (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times).

Drug: Sativex

Sativex: neutral oral pH

EXPERIMENTAL

Four sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with tap water (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times).

Drug: Sativex

Sativex: alkaline oral pH

EXPERIMENTAL

Four sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with milk of magnesia (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times).

Drug: Sativex

Interventions

Sativex DRUG

Oromucosal spray containing THC (27 mg/mL) and CBD (25 mg/mL) in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each 100 μL spray delivers 2.7 mg THC and 2.5 mg CBD.

Also known as: Nabiximols, THC/CBD spray

Sativex: acidic oral pH; Sativex: alkaline oral pH; Sativex: neutral oral pH

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is willing and able to give informed consent for participation in the study;
• Male and/or female subjects aged 18 to 50 years, inclusive;
• Subject must weigh at least 50.0 kg and have a body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive;
• Subject must be a non-smoker for at least three months prior to screening and must be willing to abstain from smoking during the study;
• Subject must be in good health as determined by the investigator from medical history, physical and oral examination findings, 12-lead standard ECG findings and clinical laboratory test results (laboratory results outside of the reference range must be documented as acceptable by both the investigator and sponsor);
• Subject is able (in the investigator's opinion) and willing to comply with all study requirements;
• Subject is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

You may not qualify if:

• Use of any prescription medications or herbal supplements within 2 weeks prior to Day 1 of the first treatment visit or any over the counter medications or supplements within 72 hours prior to first study medication administration;
• Subject has oral issues/condition likely, in the opinion of the investigator, to affect the assessment of the oromucosal absorption of Sativex;
• Subject is physically dependent on alcohol, has a history of drug or alcohol abuse within the 12 months prior to dose administration or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations;
• Subject has a positive result for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCAb) or human immunodeficiency virus (HIV) antibodies;
• Subject is currently using or has used cannabis, cannabinoid-based medications (e.g. Marinol®, Nabilone®, Cannador®) or Acomplia (rimonabant) or taranabant within 30 days of study entry (first treatment visit) and is unwilling to abstain for the duration of the study;
• Subject consumes more than five caffeinated beverages per day (e.g., five cups of tea or coffee or cans of cola) or is unwilling to abstain from consumption of caffeine-containing food and beverages throughout the study period;
• Subject has any known or suspected history or family history of schizophrenia, or other psychotic illness, history of severe personality disorder or other significant psychiatric disorder;
• Subject has any history of epilepsy as evidenced by one or more seizures in the last 12 months;
• Subject has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal product (IMP), Coca-Cola or antacid medications;
• Subject who has received an IMP within the 12 weeks prior to the screening visit, or who has received the last dose of an IMP greater than three months ago but is on extended follow-up;
• Subject with any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, may influence the result of the study or the subject's ability to participate in the study;
• Following a physical examination, the subject has any abnormalities that, in the opinion of the investigator would prevent the subject from safe participation in the study;
• Travel outside the country of residence planned during the study;
• Subjects who are vegans or have medical dietary restrictions.
• Subject has a positive urine drug (including THC), cotinine or alcohol result at screening or at Day -1 of first treatment visit; or positive urine drug (excluding THC), cotinine or alcohol result at Day -1 of subsequent treatment visits;

Sponsors & Collaborators

• GW Pharmaceuticals Ltd: lead

MeSH Terms

Conditions

Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

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

Study Officials

• James Ritter, DPhil, FRCP, FMedSci

  Quintiles Drug Research Unit at Guy's Hospital, Quintiles Ltd, 6 Newcomen Street, London SE1 1YR, United Kingdom

  PRINCIPAL INVESTIGATOR

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: September 11, 2014
• First Posted: September 15, 2014
• Study Start: August 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: October 1, 2015
• Last Updated: February 5, 2021

Record last verified: 2021-02