Study to Evaluate the Effect of Rifampicin, Ketoconazole, and Omeprazole on the Pharmacokinetics of Sativex

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT01323465
First received: March 23, 2011
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

Study to assess the effect of rifampicin, ketoconazole and omeprazole on the pharmacokinetics of a single dose of Sativex and to evaluate the safety of Sativex when given in combination with these other drugs.


Condition Intervention Phase
Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Known Inducer of CYP3A4
Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Potent Inhibitor of CYP3A4
Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a CYP2C19 Inhibitor.
Drug: Sativex and rifampicin
Drug: Sativex and ketoconazole
Drug: Sativex and omeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I, Open-label, Randomised, Crossover Study in 3 Parallel Groups to Evaluate the Effect of Rifampicin, Ketoconazole, and Omeprazole on the Pharmacokinetics of Sativex in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • Pharmacokinetic analysis - Cmax of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole [ Time Frame: Up to Day 8 ] [ Designated as safety issue: No ]
  • Pharmacokinetic analysis - AUC(0-t) of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole [ Time Frame: Up to day 8 ] [ Designated as safety issue: No ]
  • Pharmacokinetic analysis - AUC(0-inf) of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole [ Time Frame: Up to Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Up to follow up, Day 14 ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: February 2008
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence 1A
Sativex and rifampicin
Drug: Sativex and rifampicin
Single dose of 4 sprays Sativex on Day 1, Rifampicin 2 x 300 mg capsules on Days 2-10, Sativex dose of 4 sprays and rifampicin 2 x 300 mg capsules on Day 11.
Experimental: Sequence 1B
Sativex and rifampicin
Drug: Sativex and rifampicin
Rifampicin 2 x 300 mg capsules on Days 1-9, Sativex x 4 sprays and rifampicin 2 x 300 mg capsules on Day 10, Single dose of Sativex 4 sprays on Day 18.
Experimental: Sequence 2C
Sativex and ketoconazole
Drug: Sativex and ketoconazole
Single dose of 4 sprays Sativex on Day 1, ketoconazole 2 x 200 mg tablets on Days 2-5, Sativex x 4 sprays and ketoconazole 2 x 200mg on Day 6.
Experimental: Sequence 2D
Sativex and ketoconazole
Drug: Sativex and ketoconazole
Ketoconazole 2 x 200 mg tablets on Days 1-4, Sativex x 4 sprays and ketoconazole 2 x 200 mg tablets on Day 5, Single dose of 4 sprays Sativex on Day 9.
Experimental: Sequence 3E
Sativex and omeprazole
Drug: Sativex and omeprazole
Single dose of 4 sprays of Sativex on Day 1 Omeprazole 2 x 20 mg on Days 2-6. Sativex x 4 sprays and omeprazole 2 x 20 mg on Day 9.
Experimental: Sequence 3F
Sativex and omeprazole
Drug: Sativex and omeprazole
Omeprazole 2 x 20 mg on Days 1-5, Sativex x 4 sprays and omeprazole 2 x 20 mg on Day 6, Single dose of 4 sprays Sativex on Day 9.

Detailed Description:

An open-label, randomised, crossover, drug interaction study. Subjects were divided into three groups and within each group, subjects were randomised to one of two treatment sequences. Subjects received 4 sprays of Sativex alongside either doses of rifampicin, ketoconazole or omeprazole.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male subjects between 18 and 45 years of age (inclusive).
  • Subjects body mass index was between 18-30 kg/m2 (inclusive) as calculated by: Weight (kg)/height (m2).
  • No clinically significant abnormal findings on the physical examination, ECG, medical history, or clinical laboratory results during screening.
  • Subjects were to, in the opinion of the investigator, have no clinically significant abnormal findings of renal and hepatic function as determined by serum creatinine, total bilirubin, and transaminase levels.
  • Subjects were to be non-users of tobacco products (minimum of 6 months prior to the start of the study).
  • Subjects were to have a negative screen for HIV I and II, HBsAg. and antibody to hepatitis C.
  • Subjects were to have a negative urine screen for alcohol, drugs of abuse (screening only), and cotinine.
  • Subjects were to use an appropriate barrier method of contraception (condom and spermicide) in addition to having their female partner use another form of barrier contraception (e.g. female condom or occlusive cap [diaphragm or cervical vault/caps] with spermicide) during the study and for 3 months following administration of the study drug.
  • Subjects were to be able to comply with the protocol and the restrictions and the assessments therein.
  • Subjects were to give voluntary written informed consent to participate in the trial.

Exclusion Criteria:

  • Subjects were not to have a history or presence of significant cardiovascular, pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.
  • Subjects were not to have any history or presence of family history of schizophrenia, other psychotic illness, severe personality disorder, depression, or other significant psychiatric disorder.
  • Subjects were not to have a postural drop of 20 mmHG or more in systolic blood pressure at screening.
  • Subjects were not to have participated in a previous clinical trial within 90 days prior to study initiation.
  • Subjects were not to have donated plasma within 90 days prior to study initiation.
  • Subjects were not to have donated blood within 90 days prior to study initiation.
  • Subjects were not to have had an abnormal diet or substantial changes in eating habits within 30 days prior to study initiation.
  • Subjects were not to have had treatment with any known enzyme-altering agents (barbiturates, phenothiazines, cimetidine etc.) within 30 days prior to or during the study.
  • Subjects were to have no history of known hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
  • Subjects were not to use any prescription medication within 14 days prior to or during the study.
  • Subjects were not to use any over-the-counter medication within 7 days prior to or during the study.
  • Subjects were not to have a history of alcohol or drug abuse within 2 years prior to the study (subjects with a history of previous use of cannabis were not excluded unless they had used cannabis or cannabinoid based medicine within 30 days prior to study drug administration or were unwilling to abstain for the duration of the study).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01323465

Locations
United Kingdom
Guy's Drug Research Unit, Quintiles Ltd.
London, United Kingdom, SE1 1YR
Sponsors and Collaborators
GW Pharmaceuticals Ltd.
  More Information

No publications provided

Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01323465     History of Changes
Other Study ID Numbers: GWCP0602
Study First Received: March 23, 2011
Last Updated: June 13, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by GW Pharmaceuticals Ltd.:
Sativex
Cytochrome P450
Pharmacokinetics
Cannabinoids
ketoconazole
omeprazole
rifampicin

Additional relevant MeSH terms:
Ketoconazole
Rifampin
Omeprazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Anti-Ulcer Agents
Gastrointestinal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014