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

Jazz Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: 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

Treatments: Drug: Sativex and omeprazole; Drug: Sativex and ketoconazole; Drug: Sativex and rifampicin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01323465

GWCP0602

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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36 participants in 6 patient groups

Sequence 1A

Experimental group

Description:

Sativex and rifampicin

Treatment:

Drug: Sativex and rifampicin

Drug: Sativex and rifampicin

Sequence 1B

Experimental group

Description:

Sativex and rifampicin

Treatment:

Drug: Sativex and rifampicin

Drug: Sativex and rifampicin

Sequence 2C

Experimental group

Description:

Sativex and ketoconazole

Treatment:

Drug: Sativex and ketoconazole

Drug: Sativex and ketoconazole

Sequence 2D

Experimental group

Description:

Sativex and ketoconazole

Treatment:

Drug: Sativex and ketoconazole

Drug: Sativex and ketoconazole

Sequence 3E

Experimental group

Description:

Sativex and omeprazole

Treatment:

Drug: Sativex and omeprazole

Drug: Sativex and omeprazole

Sequence 3F

Experimental group

Description:

Sativex and omeprazole

Treatment:

Drug: Sativex and omeprazole

Drug: Sativex and omeprazole