Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Known Inducer of CYP3A4Phase 1NCT01323465

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

A Phase 1 study testing Sativex and rifampicin, Sativex and ketoconazole and Sativex and omeprazole in people with Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Known Inducer of CYP3A4 and Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Potent Inhibitor of CYP3A4, run by Jazz Pharmaceuticals at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: 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
What is being tested?: Sativex and rifampicin, Sativex and ketoconazole and Sativex and omeprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 1 siteUnited Kingdom
Study dates: Feb 2008to Mar 2008
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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 locations and contacts

1 site in 1 country.

United Kingdom1 site

Guy's Drug Research Unit, Quintiles Ltd.
London, SE1 1YR

Other trials in United Kingdom

About this study

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

Read the 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.

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
Being tested: Sativex and rifampicin, Sativex and ketoconazole, Sativex and omeprazole
Keywords: Sativex, Cytochrome P450, Pharmacokinetics, Cannabinoids, ketoconazole, omeprazole, rifampicin
Medical subject headings: Marijuana Abuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Sativex and rifampicinDrug
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.
Sativex and rifampicinDrug
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.
Sativex and ketoconazoleDrug
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.
Sativex and ketoconazoleDrug
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.
Sativex and omeprazoleDrug
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.
Sativex and omeprazoleDrug
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.

Study groups in NCT01323465
Study group	Role	What they receive
Sequence 1A	Experimental	Sativex and rifampicin Receives: Drug: Sativex and rifampicin
Sequence 1B	Experimental	Sativex and rifampicin Receives: Drug: Sativex and rifampicin
Sequence 2C	Experimental	Sativex and ketoconazole Receives: Drug: Sativex and ketoconazole
Sequence 2D	Experimental	Sativex and ketoconazole Receives: Drug: Sativex and ketoconazole
Sequence 3E	Experimental	Sativex and omeprazole Receives: Drug: Sativex and omeprazole
Sequence 3F	Experimental	Sativex and omeprazole Receives: Drug: Sativex and omeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetic analysis - Cmax of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole
Measured: Up to Day 8
Pharmacokinetic analysis - AUC(0-t) of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole
Measured: Up to day 8
Pharmacokinetic analysis - AUC(0-inf) of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole
Measured: Up to Day 8

Secondary outcomes (1)

Adverse Events
Measured: Up to follow up, Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Mar 2008

First posted25 Mar 2011 (estimated)
Study startFeb 2008
Primary completionMar 2008
Study completionMar 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Evaluation of Pharmacokinetics of Sativex in the Absence and Presence of a Known Inducer of CYP3A4Studies of the same condition, open and under way.
More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01323465
Sponsor's protocol ID: GWCP0602
Status last verified: Apr 2023
First submitted: 23 Mar 2011
Last updated: 10 Apr 2023
Results posted: No
Data monitoring committee: No

Publications

Stott C, White L, Wright S, Wilbraham D, Guy G. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. Springerplus. 2013 May 24;2(1):236. doi: 10.1186/2193-1801-2-236. Print 2013 Dec.
PubMed 23750331

Study at a glance

From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01323465
Acronym / sponsor ID: GWCP0602
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
Keywords: Sativex, Cytochrome P450, Pharmacokinetics, Cannabinoids, ketoconazole, omeprazole, rifampicin
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Feb 2008
Primary completion: Mar 2008 (actual)
Study completion: Mar 2008 (actual)
First posted: 25 Mar 2011 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Sequence 1A	Experimental	Drug: Sativex and rifampicinSativex and rifampicin
Sequence 1B	Experimental	Drug: Sativex and rifampicinSativex and rifampicin
Sequence 2C	Experimental	Drug: Sativex and ketoconazoleSativex and ketoconazole
Sequence 2D	Experimental	Drug: Sativex and ketoconazoleSativex and ketoconazole
Sequence 3E	Experimental	Drug: Sativex and omeprazoleSativex and omeprazole
Sequence 3F	Experimental	Drug: Sativex and omeprazoleSativex and omeprazole

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

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).

Key exclusion criteria (12 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Sativex and rifampicinSingle 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.	Drug	Sequence 1A
Sativex and rifampicinRifampicin 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.	Drug	Sequence 1B
Sativex and ketoconazoleSingle 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.	Drug	Sequence 2C
Sativex and ketoconazoleKetoconazole 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.	Drug	Sequence 2D
Sativex and omeprazoleSingle 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.	Drug	Sequence 3E
Sativex and omeprazoleOmeprazole 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.	Drug	Sequence 3F

Primary outcome

Pharmacokinetic analysis - Cmax of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole
Time frame: Up to Day 8
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
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

1 secondary outcome

Adverse Events
Time frame: Up to follow up, Day 14

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2023.
Results publication: PubMed 23750331Stott C, White L, Wright S, Wilbraham D, Guy G. A Phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of Rifampicin, Ketoconazole, and Omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. Springerplus. 2013 May 24;2(1):236. doi: 10.1186/2193-1801-2-236. Print 2013 Dec.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic analysis - Cmax of Sativex® alone and of Sativex® with concomitant administration of rifampicin, ketoconazole, and omeprazole (time frame: Up to Day 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01323465, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2023; AzTrials last refreshed its copy on 7 Nov 2026.