A Study to Assess the Pharmacokinetic (PK) Properties of Sativex® in Patients With Advanced Cancer

NCT02432612 | Withdrawn Phase 1

• 1 other identifier: GWCP1450
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (21)

• Pharmacokinetic endpoints of the analyte delta 9-tetrahydrocannabinol (THC).

  • Mean maximum plasma concentration (Cmax) of THC.

  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.

  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.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC).

  • Mean Cmax of 11-OH-THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-OH-THC.

  • Mean AUC(0-t)) of 11-OH-THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-OH-THC.

  • Mean AUC(0-∞) of 11-OH-THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-carboxy-delta 9-tetrahydrocannabinol (11-COOH-THC).

  • Mean Cmax of 11-COOH-THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-COOH-THC.

  • Mean AUC(0-t)) of 11-COOH-THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-COOH-THC.

  • Mean AUC(0-∞) of 11-COOH-THC.

  0-48 hours post dose

• Pharmacokinetic endpoints of the analyte cannabidiol (CBD).

  • Mean Cmax of CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte CBD.

  • Mean AUC(0-t) of CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte CBD.

  • Mean AUC(0-∞) of CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 6-hydroxy-cannabidiol (6-OH-CBD).

  • Mean Cmax of 6-OH-CBD.

  0-48 hours.

• Pharmacokinetic endpoints of the analyte 6-OH-CBD.

  • Mean AUC(0-t) of 6-OH-CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 6-OH-CBD.

  • Mean AUC(0-∞) of 6-OH-CBD.

  0-48 hours.

• Pharmacokinetic endpoints of the analyte 7-hydroxy-cannabidiol (7-OH-CBD).

  • Mean Cmax of 7-OH-CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 7-OH-CBD.

  • Mean AUC(0-t) of 7-OH-CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 7-OH-CBD.

  • Mean AUC(0-∞) of 7-OH-CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 7-carboxy-cannabidiol (7-COOH-CBD).

  • Mean Cmax of 7-COOH-CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 7-COOH-CBD.

  • Mean AUC(0-t) of 7-COOH-CBD.

  0-48 hours

• Pharmacokinetic endpoints of the analyte 7-COOH-CBD.

  • Mean AUC(0-∞) of 7-COOH-CBD.

  0-48 hours

Secondary Outcomes (23)

• Pharmacokinetic endpoints of the analyte THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte THC.

  0-48 hours post-dose

• Pharmacokinetic endpoints of the analyte 11-OH-THC.

  0-48 hours post-dose

Study Arms (1)

Sativex

EXPERIMENTAL

Sativex will be administered by trained, clinical trial personnel, via a pump action oromucosal spray. Sativex will be administered as 2 actuations (sprays) under the tongue or inside the cheeks every 4 minutes until 6 sprays have been administered. Following the administration of the first and second set of 2 actuations, patients will be offered 50 mL water to drink; and following the final set of 2 actuations, 100 mL of water will be offered (i.e., a total of 200 mL water will be offered during the Sativex dosing). There must be a period of at least 2 minutes and no more than 3 minutes between Sativex administration and consumption of water. Patients will not be permitted their regular medication until 2 hours post dose of investigational medicinal product (IMP) to minimize any possible drug interactions.

Drug: Sativex

Interventions

Sativex DRUG

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.

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

Sativex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

For inclusion in the trial subjects must fulfil ALL of the following criteria: * The subject is aged ≥18 years. * The subject has advanced cancer for which there is no known curative therapy. * The subject has a clinical diagnosis of cancer related pain, is currently taking Step III opioid therapy and is willing to continue on their current dosing regimen throughout the Inpatient/Treatment Period of the trial. * The subject is willing and able to give written informed consent. * The subject is willing and able to comply with all trial requirements. The subject may not enter the trial if ANY of the following apply: * The subject is receiving intrathecal opioids via pump mechanism. * The subject is currently using or has used cannabis or cannabinoid based medications within 30 days of trial entry and is unwilling to abstain for the duration of the trial. * The subject has any known or suspected history of a substance abuse/dependence disorder (including opiate abuse/dependence prior to the diagnosis of cancer); current heavy alcohol consumption (more than 60 grams of pure alcohol per day for men, and more than 40 grams of pure alcohol per day for women) and unwilling to abstain from alcohol for 24 hours prior to and during trial visits; current use of an illicit drug or current non prescribed use of any prescription drug. * The subject has a history of epilepsy as evidenced by one or more seizures in the last 12 months. * The subject has any known or suspected history or family history of schizophrenia, or other psychotic illness, history of severe personality disorder or other severe significant psychiatric disorder other than depression associated with the underlying condition. * The subject has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP. * The subject has significant cardiac disease, or has a cardiac disorder that in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction, or has a secondary or tertiary atrioventricular block, or evidence of clinically significant cardiac disease on ECG at the Screening Visit. * The subject has significantly impaired renal function as evidenced by a creatinine clearance (based on measured serum creatinine level) lower than 40 mL/min at Visit 1. * The subject has significantly impaired hepatic function at Visit 1 (alanine aminotransferase \[ALT\] \>5 upper limit of normal (ULN) or total bilirubin \[TBL\] \> 2 ULN). If the ALT or aspartate aminotransferase \[AST\] \>3 ULN and the TBL \>2 ULN \[or international normalized ratio \[INR\] \>1.5\]) this subject must not enter the trial. * The subject is a female of childbearing potential, or a male patient whose partner is of childbearing potential, is unwilling to ensure that they and/or their partner use a highly effective method of contraception, including female sterilization (ie, documented bilateral tubal ligation), male sterilization, established use of hormonal methods of contraception (oral, implanted or transdermal), an intrauterine device or intrauterine system, or true abstinence. * Female subject who is pregnant, lactating or planning pregnancy during the course of the trial and for 3 months thereafter. * The subject has received a non approved IMP within 30 days or 5 times the half-life of the IMP (whichever is greater) prior to the Screening Visit. * The subject has any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the trial, or may influence the result of the trial, or the patient's ability to participate in the trial. * The subject was previously enrolled in the current trial or any other Sativex clinical trial for cancer pain. * The subject is unwilling to abstain from the consumption of grapefruit products during the week prior to and throughout the Inpatient/Treatment period.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• GW Pharmaceuticals Ltd: lead

MeSH Terms

Interventions

nabiximols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: May 4, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: March 2, 2016

Record last verified: 2016-03