Healthy VolunteersPhase 1NCT02240160

A Randomised, Open-label, Three-way Crossover Study to Assess the Pharmacokinetics and Safety of Single Doses of Four Sprays of Sativex® in a Range of Oral pH Environments in Healthy Subjects

A Phase 1 study testing Sativex in people with Healthy Volunteers, run by GW Pharmaceuticals Ltd.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

To evaluate the effect of oral pH on the pharmacokinetics (PK) of a single oromucosal dose of Sativex (four sprays containing 10.8 mg Δ9 tetrahydrocannabinol (THC) and 10 mg cannabidiol (CBD)) by comparing the PK profile of Sativex in healthy subjects. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: Sativex
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: No sites listed yet
Study dates: Aug 2014to Oct 2015
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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subject is willing and able to give informed consent for participation in the study;
Male and/or female subjects aged 18 to 50 years, inclusive;
Subject must weigh at least 50.0 kg and have a body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive;
Subject must be a non-smoker for at least three months prior to screening and must be willing to abstain from smoking during the study;
Subject must be in good health as determined by the investigator from medical history, physical and oral examination findings, 12-lead standard ECG findings and clinical laboratory test results (laboratory results outside of the reference range must be documented as acceptable by both the investigator and sponsor);
Subject is able (in the investigator's opinion) and willing to comply with all study requirements;
Subject is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

Who cannot join

Use of any prescription medications or herbal supplements within 2 weeks prior to Day 1 of the first treatment visit or any over the counter medications or supplements within 72 hours prior to first study medication administration;
Subject has oral issues/condition likely, in the opinion of the investigator, to affect the assessment of the oromucosal absorption of Sativex;
Subject is physically dependent on alcohol, has a history of drug or alcohol abuse within the 12 months prior to dose administration or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations;
Subject has a positive result for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCAb) or human immunodeficiency virus (HIV) antibodies;
Subject is currently using or has used cannabis, cannabinoid-based medications (e.g. Marinol®, Nabilone®, Cannador®) or Acomplia (rimonabant) or taranabant within 30 days of study entry (first treatment visit) and is unwilling to abstain for the duration of the study;
Subject consumes more than five caffeinated beverages per day (e.g., five cups of tea or coffee or cans of cola) or is unwilling to abstain from consumption of caffeine-containing food and beverages throughout the study period;

Show all 19Show fewer

Subject has any known or suspected history or family history of schizophrenia, or other psychotic illness, history of severe personality disorder or other significant psychiatric disorder;
Subject has any history of epilepsy as evidenced by one or more seizures in the last 12 months;
Subject has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal product (IMP), Coca-Cola or antacid medications;
Subject who has received an IMP within the 12 weeks prior to the screening visit, or who has received the last dose of an IMP greater than three months ago but is on extended follow-up;
Subject with any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, may influence the result of the study or the subject's ability to participate in the study;
Following a physical examination, the subject has any abnormalities that, in the opinion of the investigator would prevent the subject from safe participation in the study;
Travel outside the country of residence planned during the study;
Subjects who are vegans or have medical dietary restrictions.
Subject has a positive urine drug (including THC), cotinine or alcohol result at screening or at Day -1 of first treatment visit; or positive urine drug (excluding THC), cotinine or alcohol result at Day -1 of subsequent treatment visits;
Female subjects of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use two effective forms of contraception e.g, oral contraception, double barrier or intra-uterine device (IUD), during the study and for three months thereafter (however a male condom should not be used in conjunction with a female condom);
Female subject who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter;
Subjects who have donated or lost more than 450 mL of blood in the 60 days prior to screening or are unwilling to abstain from donation of blood during the study;
Subject has previously been randomised into this study.

About this study

The primary clinical hypothesis is that there will be an effect of oral pH on the PK of Sativex when administered as a single oromucosal dose (four sprays).

Read the detailed description

This is a Phase I, randomised, open-label, three-way crossover study to assess the effects of oral pH on the PK of Sativex. Subjects will receive each of the following treatments in a random order across three residential treatment visits:

Treatment A (acidic oral pH): Sativex (four sprays) after pre-treatment with Coca-Cola;
Treatment B (neutral oral pH): Sativex (four sprays) after pre-treatment with tap water;
Treatment C (alkaline oral pH): Sativex (four sprays) after pre-treatment with an oral suspension of magnesium hydroxide (milk of magnesia).

The target pH for each treatment will be determined from the results of a pilot study.

Each dose administration will be separated by at least seven days. Study subjects will participate in a total of five study visits.

Conditions: Healthy Volunteers
Being tested: Sativex
Keywords: Sativex, Pharmacokinetics, Oral pH
Medical subject headings: Marijuana Abuse

What participants receive

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

SativexDrug
Also called Nabiximols, THC/CBD spray
Oromucosal spray containing THC (27 mg/mL) and CBD (25 mg/mL) in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each 100 μL spray delivers 2.7 mg THC and 2.5 mg CBD.

Study groups in NCT02240160
Study group	Role	What they receive
Sativex: acidic oral pH	Experimental	Four sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with Coca-Cola (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times). Receives: Drug: Sativex
Sativex: neutral oral pH	Experimental	Four sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with tap water (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times). Receives: Drug: Sativex
Sativex: alkaline oral pH	Experimental	Four sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with milk of magnesia (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times). Receives: Drug: Sativex

What is being measured

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

Pharmacokinetic parameters of THC: Cmax, AUC(0-t), and AUC(0-∞)
Mean highest observed plasma concentration of the measured concentration-time profile (Cmax), area under the concentration-time curve from administration to the last sampling point (AUC(0-t)), and area under the concentration-time curve extrapolated to infinity (AUC(0-∞)) of THC are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of CBD: Cmax, AUC(0-t), and AUC(0-∞)
Mean Cmax, AUC(0-t), and AUC(0-∞) of CBD are presented.
Measured: 0-24 hours post-dose

Secondary outcomes (16)

Pharmacokinetic parameters of 11-hydroxy-CBD (11-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)
Mean Cmax, AUC(0-t), and AUC(0-∞) of 11-OH-CBD are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of 7-hydroxy-CBD (7-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)
Mean Cmax, AUC(0-t), and AUC(0-∞) of 7-OH-CBD are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of 6-hydroxy-CBD (6-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)
Mean Cmax, AUC(0-t), and AUC(0-∞) of 6-OH-CBD are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of THC: t½ and Tmax
Mean terminal elimination half-life (t½) and time to maximum plasma concentration (Tmax) of THC are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of 11-OH-CBD: t½ and Tmax
Mean t½ and Tmax of 11-OH-CBD are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of CBD: t½ and Tmax
Mean t½ and Tmax of CBD are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of 7-OH-CBD: t½ and Tmax
Mean t½ and Tmax of 7-OH-CBD are presented.
Measured: 0-24 hours post-dose
Pharmacokinetic parameters of 6-OH-CBD: t½ and Tmax
Mean t½ and Tmax of 6-OH-CBD are presented.
Measured: 0-24 hours post-dose
Total body clearance (CL/F) of THC and CBD from plasma
Mean total body clearance of THC and CBD from plasma is presented.
Measured: 0-24 hours post-dose
The incidence of adverse events as 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 the follow-up visit.
Measured: From screening to follow-up, an expected average of 35 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.
Measured: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in 12-lead electrocardiogram (ECG) 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.
Measured: From screening to follow-up, an expected average of 35 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.
Measured: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in vital signs, relative to pre-treatment baseline
The number of subjects with a change in vital signs (systolic blood pressure, diastolic blood pressure, pulse rate) indicative of an adverse event, relative to the pre-treatment baseline, is presented.
Measured: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in body temperature, relative to pre-treatment baseline
The number of subjects with a change in body temperature indicative of an adverse event, relative to the pre-treatment baseline, is presented.
Measured: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in body weight, relative to pre-treatment baseline
The number of subjects with a change in body weight indicative of an adverse event, relative to the pre-treatment baseline, is presented.
Measured: From screening to follow-up, an expected average of 35 days

Timeline

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

Aug 2014Oct 2015

First posted15 Sep 2014 (estimated)
Study startAug 2014
Primary completionAug 2014
Study completionOct 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
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: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02240160
Sponsor's protocol ID: GWCP10116
Other IDs: 2013-004459-19
Status last verified: Feb 2021
First submitted: 11 Sep 2014
Last updated: 5 Feb 2021
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Open-label, Three-way Crossover Study to Assess the Pharmacokinetics and Safety of Single Doses of Four Sprays of Sativex® in a Range of Oral pH Environments in Healthy Subjects
ClinicalTrials.gov ID: NCT02240160
Acronym / sponsor ID: GWCP10116
Conditions: Healthy Volunteers
Keywords: Sativex, Pharmacokinetics, Oral pH
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 6 participants (actual)
Lead sponsor: GW Pharmaceuticals LtdIndustry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: Aug 2014 (actual)
Study completion: Oct 2015 (actual)
First posted: 15 Sep 2014 (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.

The primary clinical hypothesis is that there will be an effect of oral pH on the PK of Sativex when administered as a single oromucosal dose (four sprays).

Detailed description

Treatment A (acidic oral pH): Sativex (four sprays) after pre-treatment with Coca-Cola;
Treatment B (neutral oral pH): Sativex (four sprays) after pre-treatment with tap water;
Treatment C (alkaline oral pH): Sativex (four sprays) after pre-treatment with an oral suspension of magnesium hydroxide (milk of magnesia).

The target pH for each treatment will be determined from the results of a pilot study.

Each dose administration will be separated by at least seven days. Study subjects will participate in a total of five study visits.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Sativex: acidic oral pH	Experimental	Drug: SativexFour sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with Coca-Cola (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times).
Sativex: neutral oral pH	Experimental	Drug: SativexFour sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with tap water (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times).
Sativex: alkaline oral pH	Experimental	Drug: SativexFour sprays of Sativex taken within two minutes of pH measurement immediately following oral pre-treatment with milk of magnesia (30 mL held in the mouth for 45-60 seconds then spat out, repeated three times).

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Subject is willing and able to give informed consent for participation in the study;
Male and/or female subjects aged 18 to 50 years, inclusive;
Subject must weigh at least 50.0 kg and have a body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive;
Subject must be a non-smoker for at least three months prior to screening and must be willing to abstain from smoking during the study;
Subject must be in good health as determined by the investigator from medical history, physical and oral examination findings, 12-lead standard ECG findings and clinical laboratory test results (laboratory results outside of the reference range must be documented as acceptable by both the investigator and sponsor);

Key exclusion criteria (19 listed)

Use of any prescription medications or herbal supplements within 2 weeks prior to Day 1 of the first treatment visit or any over the counter medications or supplements within 72 hours prior to first study medication administration;
Subject has oral issues/condition likely, in the opinion of the investigator, to affect the assessment of the oromucosal absorption of Sativex;
Subject is physically dependent on alcohol, has a history of drug or alcohol abuse within the 12 months prior to dose administration or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations;
Subject has a positive result for the presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCAb) or human immunodeficiency virus (HIV) antibodies;
Subject is currently using or has used cannabis, cannabinoid-based medications (e.g. Marinol®, Nabilone®, Cannador®) or Acomplia (rimonabant) or taranabant within 30 days of study entry (first treatment visit) and is unwilling to abstain for the duration of the study;

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
SativexAlso: Nabiximols, THC/CBD sprayOromucosal spray containing THC (27 mg/mL) and CBD (25 mg/mL) in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each 100 μL spray delivers 2.7 mg THC and 2.5 mg CBD.	Drug	Sativex: acidic oral pH, Sativex: alkaline oral pH, Sativex: neutral oral pH

Primary outcome

Pharmacokinetic parameters of THC: Cmax, AUC(0-t), and AUC(0-∞)
Time frame: 0-24 hours post-dose
Mean highest observed plasma concentration of the measured concentration-time profile (Cmax), area under the concentration-time curve from administration to the last sampling point (AUC(0-t)), and area under the concentration-time curve extrapolated to infinity (AUC(0-∞)) of THC are presented.
Pharmacokinetic parameters of CBD: Cmax, AUC(0-t), and AUC(0-∞)
Time frame: 0-24 hours post-dose
Mean Cmax, AUC(0-t), and AUC(0-∞) of CBD are presented.

16 secondary outcomes

Pharmacokinetic parameters of 11-hydroxy-CBD (11-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of 7-hydroxy-CBD (7-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of 6-hydroxy-CBD (6-OH-CBD): Cmax, AUC(0-t), and AUC(0-∞)
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of THC: t½ and Tmax
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of 11-OH-CBD: t½ and Tmax
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of CBD: t½ and Tmax
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of 7-OH-CBD: t½ and Tmax
Time frame: 0-24 hours post-dose
Pharmacokinetic parameters of 6-OH-CBD: t½ and Tmax
Time frame: 0-24 hours post-dose
Total body clearance (CL/F) of THC and CBD from plasma
Time frame: 0-24 hours post-dose
The incidence of adverse events as measure of subject safety
Time frame: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in physical and oral examination results, relative to pre-treatment baseline
Time frame: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in 12-lead electrocardiogram (ECG) results, relative to pre-treatment baseline
Time frame: From screening to follow-up, an expected average of 35 days
The number of subjects with clinically significant changes in laboratory test parameters, relative to pre-treatment baseline
Time frame: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in vital signs, relative to pre-treatment baseline
Time frame: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in body temperature, relative to pre-treatment baseline
Time frame: From screening to follow-up, an expected average of 35 days
The number of subjects with a clinically significant change in body weight, relative to pre-treatment baseline
Time frame: From screening to follow-up, an expected average of 35 days

Results and safety

The study was stopped early. Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2021.

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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.

James Ritter, DPhil, FRCP, FMedSci principal investigator

Quintiles Drug Research Unit at Guy's Hospital, Quintiles Ltd, 6 Newcomen Street, London SE1 1YR, United Kingdom

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sativex in people with Healthy Volunteers, run by GW Pharmaceuticals Ltd.

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 7 inclusion and 19 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: stopped early, as of the sponsor's last update on 5 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

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 was stopped early. Results are not available in the source record.

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 parameters of THC: Cmax, AUC(0-t), and AUC(0-∞) (time frame: 0-24 hours post-dose). The study lists 2 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 NCT02240160.

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 5 Feb 2021.