The purpose of this study is to evaluate the pharmacokinetics (PK) of a single oromucosal dose of Sativex in subjects with advanced cancer currently on background Step III opioid therapy.
This is an open-label, multiple-centre, single dose clinical trial to assess the PK of a single oromucosal dose of Sativex in subjects with advanced cancer who are currently on background Step III opioid therapy. A minimum of 25 subjects ≥18 years with advanced cancer will be needed for the assessment of the primary objective of the trial. The Screening Visit (Visit 1) will be performed within -10 to -2 days prior to dosing. For the Screening Visit, subjects will attend on an outpatient basis. Subjects will be checked into the clinical research facility on Day -1 and will be confined to the clinical research facility for the Inpatient/Treatment Period (Day -1 to Day 3) (Visit 2). Subjects will be administered a single oromucosal dose of Sativex on Day 1 (time \[t\]=0). Fourteen PK blood samples will be taken from Day 1 to Day 3 during Visit 2: one predose sample and 13 postdose samples at the following time points after dosing: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours postdose. Subjects will be discharged from the clinical research facility after the 48-hour PK blood sample has been taken and final safety assessments are completed. Subjects who discontinue from the trial prior to the completion of the PK blood draws will undergo the safety evaluations scheduled for Day 3. The Safety Follow-up Call (Visit 3) will be made 7 (+2) days after dosing on Day 1. Subjects with any new adverse events (AEs) or clinical laboratory abnormalities will be asked to return for safety follow-up. The expected duration for trial participation (including Screening Visit, Inpatient/Treatment Period, and Safety Follow-up Call) for each individual subject is a maximum of 19 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Sativex is supplied as a liquid containing 27 mg/mL Δ9-tetrahydrocannabinol (THC) and 25 mg/mL Cannabidiol (CBD) plus peppermint flavoring. Each 100 µL actuation of the pump-action spray delivers 100 µL 27 mg THC and 25 mg CBD.
Pharmacokinetic endpoints of the analyte delta 9-tetrahydrocannabinol (THC).
• Mean maximum plasma concentration (Cmax) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte THC.
• Mean area under the concentration-time curve calculated from time zero to the last observable concentration at time t (AUC(0-t)) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte THC.
• Mean area under the concentration-time curve from time zero to infinity (AUC(0-∞)) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC).
• Mean Cmax of 11-OH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-OH-THC.
• Mean AUC(0-t)) of 11-OH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-OH-THC.
• Mean AUC(0-∞) of 11-OH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-carboxy-delta 9-tetrahydrocannabinol (11-COOH-THC).
• Mean Cmax of 11-COOH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-COOH-THC.
• Mean AUC(0-t)) of 11-COOH-THC.
Time frame: 0-48 hours post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Pharmacokinetic endpoints of the analyte 11-COOH-THC.
• Mean AUC(0-∞) of 11-COOH-THC.
Time frame: 0-48 hours post dose
Pharmacokinetic endpoints of the analyte cannabidiol (CBD).
• Mean Cmax of CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte CBD.
• Mean AUC(0-t) of CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte CBD.
• Mean AUC(0-∞) of CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 6-hydroxy-cannabidiol (6-OH-CBD).
• Mean Cmax of 6-OH-CBD.
Time frame: 0-48 hours.
Pharmacokinetic endpoints of the analyte 6-OH-CBD.
• Mean AUC(0-t) of 6-OH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 6-OH-CBD.
• Mean AUC(0-∞) of 6-OH-CBD.
Time frame: 0-48 hours.
Pharmacokinetic endpoints of the analyte 7-hydroxy-cannabidiol (7-OH-CBD).
• Mean Cmax of 7-OH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 7-OH-CBD.
• Mean AUC(0-t) of 7-OH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 7-OH-CBD.
• Mean AUC(0-∞) of 7-OH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 7-carboxy-cannabidiol (7-COOH-CBD).
• Mean Cmax of 7-COOH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 7-COOH-CBD.
• Mean AUC(0-t) of 7-COOH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte 7-COOH-CBD.
• Mean AUC(0-∞) of 7-COOH-CBD.
Time frame: 0-48 hours
Pharmacokinetic endpoints of the analyte THC.
• Mean half-life (t1/2) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte THC.
• Mean time to maximum plasma concentration (tmax) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte THC.
• Mean apparent clearance of drug from plasma after extravascular administration (CL/F) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte THC.
• Mean apparent volume of distribution (Vd/F) of THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-OH-THC.
• Mean t1/2 of 11-OH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-OH-THC.
• Mean tmax of 11-OH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-COOH-THC.
• Mean t1/2 of 11-COOH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 11-COOH-THC.
• Mean tmax of 11-COOH-THC.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte CBD.
• Mean t1/2 of CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte CBD.
• Mean tmax of CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte CBD.
• Mean CL/F of CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte CBD.
• Mean Vd/F of CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 6-OH-CBD.
• Mean t1/2 of 6-OH-CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 6-OH-CBD.
• Mean tmax of 6-OH-CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 7-OH-CBD.
• Mean t1/2 of 7-OH-CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 7-OH-CBD.
• Mean tmax of 7-OH-CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 7-COOH-CBD.
• Mean t1/2 of 7-COOH-CBD.
Time frame: 0-48 hours post-dose
Pharmacokinetic endpoints of the analyte 7-COOH-CBD.
• Mean tmax of 7-COOH-CBD.
Time frame: 0-48 hours post-dose
The incidence of adverse events as a measure of subject safety.
The number of subjects who experienced an adverse event during the study is presented. The time-frame for adverse event reporting was from screening to follow-up visit.
Time frame: From screening to follow-up (a maximum of 19 days).
The number of subjects with a clinically significant change in physical and oral examination results, relative to pre-treatment baseline.
The number of subjects with a change in physical and oral examination results indicative of an adverse event, relative to the pre-treatment baseline, is presented.
Time frame: From screening to follow-up (a maximum of 19 days)
The number of subjects with a clinically significant change in in 12-lead ECG (electrocardiogram) results, relative to pre-treatment baseline.
The number of subjects with a change in ECG results indicative of an adverse event, relative to the pre-treatment baseline, is presented.
Time frame: From screening to follow-up (a maximum of 19 days)
The number of subjects with clinically significant changes in laboratory test parameters, relative to pre-treatment baseline.
The number of subjects with clinically significant changes in serum biochemistry, haematology and urinalysis, relative to the pre-treatment baseline, is presented.
Time frame: From screening to follow-up (a maximum of 19 days)
The number of subjects with a clinically significant change in vital signs, relative to pre-treatment baseline.
The number of subjects with a clinically significant change in vital signs (supine/sitting blood pressure and pulse rate) indicative of an adverse event relative to the pre-treatment baseline, is presented.
Time frame: From screening to follow-up (a maximum of 19 days)