Effects of Sativex on ECGPhase 1NCT01322139

Sativex Thorough QT/QTc Study

A Phase 1 study of Effects of Sativex on ECG, run by Jazz Pharmaceuticals at 1 site in Canada.

Completed

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

Trial summary

This study was to evaluate effects of Sativex on electrocardiogram (ECG) traces when administered at its therapeutic dose of 8 sprays per day and at multiples of the therapeutic dose (24 or 36 sprays per day), and to evaluate its safety and tolerability. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Effects of Sativex on ECG
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 258 participants
Where: 1 siteCanada
Study dates: Dec 2007to Jun 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
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male and female subjects 18 to 45 years of age.
Body Mass Index (BMI) within the range of 19 to 29.9 kg/m2, and a minimum weight of at least 50 kg at screening.
Non-users of tobacco products (minimum of 6 months)
Free from any clinically significant abnormality on the basis of medical history, vital signs, physical examination, ECG, and laboratory evaluation at screening and admission to the treatment session, as judged by the investigator or designee.
Systolic blood pressure between 90 to 140 mmHg and diastolic blood pressure between 50 and 90 mmHg at screening and admission to the treatment session.
Subjects with reproductive potential required to practice abstinence or be using and willing to continue using a medically acceptable form of birth control for at least one month prior to screening (at least 3 months for oral contraceptives) and for at least 60 days after the last study drug administration.

Show all 10Show fewer

Female subjects required to have a negative serum pregnancy test at screening and admission to the treatment session.
Subjects must have been able to speak, read and understand English sufficiently to understand the nature of the study, to provide written informed consent, and to allow completion of all study assessments.
Subjects must have understood and provided written informed consent prior to initiation of any protocol-specific procedures.
Subjects must have been willing and able to abide by all study requirements and restrictions.

Who cannot join

History or presence of drug or alcohol abuse or dependence (as determined by the Diagnostic and Statistical manual, 4th Revision [DSM-IV] for abuse and dependence), including subjects who had ever been in a drug rehabilitation program.
Clinically significant abnormalities on oral or physical examination, medical history, ECG, vital signs, or laboratory values at screening or admission to the treatment session, as judged by the investigator or designee.
Any known or suspected history (including family history) of schizophrenia or other psychotic illness. Presence or history of an organic brain disorder or seizure disorder deemed clinically significant by the investigator.
History or presence of clinically significant pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition, which in the opinion of the investigator would have jeopardised the safety of the subject or the validity of the study results.
Known cardiovascular condition or history of a cardiovascular condition at screening.
Pulse rate at rest less than 45 or greater than 100 beats per minute.

Show all 24Show fewer

Abnormal screening ECG indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS greater than 109 msec, QTc greater than 450 msec, PR interval greater than 200 msec. Any rhythm other than sinus rhythm, which was interpreted by the investigator to be clinically significant.
History of torsade de pointes or risk factors for torsade de pointes (e.g. heart failure, hypokalemia, family history of Long QT syndrome).
Postural drop of 20 mmHg or more in systolic blood pressure at screening.
Use of non-prescription drug within 7 days prior to the first drug administration (in particular iron and antacids). Subjects who had taken over-the-counter medication could still be entered into the study, if in the opinion of the investigator or designee, the medication received would not interfere with the study procedures or data integrity or compromise the safety of the subject.
Use of any prescription medications (except acceptable forms of birth control and hormone replacement), natural health products, or recreational drugs within 14 days or 5 elimination half-lives (whichever was longer) prior to first drug administration or throughout the study, unless in the opinion of the investigator or designee, the product would not interfere with the study procedures or data integrity or compromise the safety of the subject. In particular medications that prolong the QT/QTc interval (e.g. erythromycin, antipsychotics, tricyclic antidepressants)were strictly avoided.
Currently using cannabis or tetrahydrocannabinol (THC)-containing medicines (as shown by positive urine drug screen). Subjects who had used natural or synthetic cannabinoid based medications (including Sativex, Marinol or Acomplia [rimonabant]) within 3 months prior to study entry and were unwilling to abstain for the duration of the study.
Habituation to analgesic drugs (i.e. routine use of oral analgesics 5 or more times per week).
Positive urine drug screen upon presentation for screening or at admission to the treatment session.
Positive breath alcohol test at screening or at admission to the treatment session.
Female subjects who were pregnant or lactating or who were planning to become pregnant within 60 days of last study drug administration.
Inability to refrain from consuming caffeine (including caffeine pills, cola, tea, coffee, energy drinks, or any other caffeinated product) for at least nine days.
History of allergy or hypersensitivity to cannabinoids, propylene glycol, ethanol, peppermint oil, moxifloxacin or other quinolone antimicrobials, related drugs, or any of the drug excipients or other drug product components.
Positive for Hepatitis B, Hepatitis C, or HIV at screening.
Donation of 50 mL to 499 mL whole blood within 30 days or donation of more than 499 mL whole blood within 56 days of admission to the treatment session.
Current or pending legal charges or currently on probation.
Treatment with any investigational drug within 30 days prior to screening.
Study site or Sponsor employee or relative of an employee who was directly involved in the study.
A subject who, in the opinion of the investigator or designee, was not considered to be suitable and was unlikely to comply with the study protocol for any reason.

Trial locations and contacts

1 site in 1 country.

Canada1 site

DecisionLine Clinical Research Corporation
Toronto, Ontario, M5V 2T3

Other trials in Canada

About this study

Official title: A Multiple-Dose, Randomized, Double-Blind, Placebo- and Active-Controlled, Four-Arm, Parallel Group Thorough QT/QTc Study to Evaluate the Electrophysiologic Effects of Sativex.

Read the detailed description

This is a multiple-dose, randomized, double-blind, double-dummy, placebo- and active-controlled, four arm, parallel group study to evaluate the effect of Sativex on the QT/QTc interval.

Within 30 days of screening, eligible subjects were randomized to one of four treatment groups. Baseline ECG measurements were recorded at specified times and the following day, subjects commenced five days treatment with Sativex or placebo. On Day 5, subjects then received either moxifloxacin 400 mg (Group 4) or moxifloxacin placebo (Groups 1, 2 and 3). Triplicate ECG measurements and pharmacokinetic samples were collected on Day 5. On days 1-5, Safety ECG measurements were also collected at pre-dose and 2 hours post-dose. Subjects returned to the study centre for an outpatient safety follow-up visit approximately 10-14 days after their last dose of study medication.

Conditions: Effects of Sativex on ECG
Being tested: Placebo spray and oral moxifloxacin placebo, Sativex spray and oral moxifloxacin placebo, Placebo spray and moxifloxacin
Keywords: Sativex, Cannabinoid, Electrocardiogram, QT interval
Medical subject headings: Marijuana Abuse

What participants receive

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

Placebo spray and oral moxifloxacin placeboDrug
24 or 36 placebo sprays (12 or 18 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin placebo on Day 5.
Sativex spray and oral moxifloxacin placeboDrug
8 Sativex sprays (4 sprays twice daily every 12 hours) + 16 or 28 placebo sprays (8 or 14 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin placebo on Day 5.
Sativex spray and oral moxifloxacin placeboDrug
24 or 36 Sativex sprays (12 or 18 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin placebo on Day 5.
Placebo spray and moxifloxacinDrug
24 or 36 placebo sprays (12 or 18 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin 400 mg tablet on Day 5.

Study groups in NCT01322139
Study group	Role	What they receive
High dose placebo and oral moxifloxacin placebo	Placebo comparator	24 or 36 placebo sprays (12 or 18 sprays twice daily) for 5 days and single oral moxifloxacin placebo on Day 5. Receives: Drug: Placebo spray and oral moxifloxacin placebo
Low dose Sativex and oral moxifloxacin placebo	Active comparator	8 Sativex sprays (4 sprays twice daily) + 16 or 28 placebo sprays (8 or 14 sprays twice daily) for 5 days and single oral moxifloxacin placebo on Day 5. Receives: Drug: Sativex spray and oral moxifloxacin placebo
High dose Sativex and oral moxifloxacin placebo	Active comparator	24 or 36 Sativex sprays (12 or 18 sprays twice daily) for 5 days and single oral moxifloxacin placebo on Day 5. Receives: Drug: Sativex spray and oral moxifloxacin placebo
High dose placebo and single oral moxifloxacin 400 mg tablet	Active comparator	24 or 36 placebo sprays (12 or 18 sprays twice daily) for 5 days and single oral moxifloxacin 400 mg tablet on Day 5. Receives: Drug: Placebo spray and moxifloxacin

What is being measured

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

Time-matched change from baseline in QTc based on an individual correction (QTcl)
Measured: 5 days

Secondary outcomes (14)

QTc with Fridericia correction method (QTcF) and the QTc with Bazett correction (QTcB)
Measured: 5 days
Heart Rate
Measured: 5 days
PR interval
Measured: 5 days
QRS interval
Measured: 5 days
Uncorrected QT interval
Measured: 5 days
Change in ECG morphological patterns
Measured: 5 days
Correlation between the QTcl change from baseline and plasma concentrations of the parent metabolites
Measured: 5 days
Adverse Events
Measured: Up to 2 weeks after final dose
Clinical laboratory parameters
Measured: Up to 2 weeeks after final dose
Vital signs
Measured: Up to 2 weeks after final dose
Oral and physical examination
Measured: Up to 2 weeks after final dose
Peak plasma concentration (Cmax)
Measured: Days 5 and 6
Time to peak plasma concentration (Tmax)
Measured: Days 5 and 6
Area under the concentration curve (AUC(0-t) and AUC(0-inf))
Measured: Days 5 and 6

Timeline

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

Dec 2007Jun 2008

First posted24 Mar 2011 (estimated)
Study startDec 2007
Primary completionJun 2008
Study completionJun 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 Effects of Sativex on ECGStudies 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: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 258 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01322139
Sponsor's protocol ID: GWCP0607
Status last verified: Apr 2023
First submitted: 23 Mar 2011
Last updated: 10 Apr 2023
Results posted: No
Data monitoring committee: No

Publications

Sellers EM, Schoedel K, Bartlett C, Romach M, Russo EB, Stott CG, Wright S, White L, Duncombe P, Chen CF. A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray. Clin Pharmacol Drug Dev. 2013 Jul;2(3):285-94. doi: 10.1002/cpdd.36. Epub 2013 May 14.
PubMed 27121791

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 Multiple-Dose, Randomized, Double-Blind, Placebo- and Active-Controlled, Four-Arm, Parallel Group Thorough QT/QTc Study to Evaluate the Electrophysiologic Effects of Sativex.
ClinicalTrials.gov ID: NCT01322139
Acronym / sponsor ID: GWCP0607
Conditions: Effects of Sativex on ECG
Keywords: Sativex, Cannabinoid, Electrocardiogram, QT interval
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 258 participants (actual)
Lead sponsor: Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Dec 2007
Primary completion: Jun 2008 (actual)
Study completion: Jun 2008 (actual)
First posted: 24 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

This is a multiple-dose, randomized, double-blind, double-dummy, placebo- and active-controlled, four arm, parallel group study to evaluate the effect of Sativex on the QT/QTc interval.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
High dose placebo and oral moxifloxacin placebo	Placebo comparator	Drug: Placebo spray and oral moxifloxacin placebo24 or 36 placebo sprays (12 or 18 sprays twice daily) for 5 days and single oral moxifloxacin placebo on Day 5.
Low dose Sativex and oral moxifloxacin placebo	Active comparator	Drug: Sativex spray and oral moxifloxacin placebo8 Sativex sprays (4 sprays twice daily) + 16 or 28 placebo sprays (8 or 14 sprays twice daily) for 5 days and single oral moxifloxacin placebo on Day 5.
High dose Sativex and oral moxifloxacin placebo	Active comparator	Drug: Sativex spray and oral moxifloxacin placebo24 or 36 Sativex sprays (12 or 18 sprays twice daily) for 5 days and single oral moxifloxacin placebo on Day 5.
High dose placebo and single oral moxifloxacin 400 mg tablet	Active comparator	Drug: Placebo spray and moxifloxacin24 or 36 placebo sprays (12 or 18 sprays twice daily) for 5 days and single oral moxifloxacin 400 mg tablet on Day 5.

Who may qualify

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

Key inclusion criteria (10 listed)

Healthy male and female subjects 18 to 45 years of age.
Body Mass Index (BMI) within the range of 19 to 29.9 kg/m2, and a minimum weight of at least 50 kg at screening.
Non-users of tobacco products (minimum of 6 months)
Free from any clinically significant abnormality on the basis of medical history, vital signs, physical examination, ECG, and laboratory evaluation at screening and admission to the treatment session, as judged by the investigator or designee.
Systolic blood pressure between 90 to 140 mmHg and diastolic blood pressure between 50 and 90 mmHg at screening and admission to the treatment session.

Key exclusion criteria (24 listed)

History or presence of drug or alcohol abuse or dependence (as determined by the Diagnostic and Statistical manual, 4th Revision [DSM-IV] for abuse and dependence), including subjects who had ever been in a drug rehabilitation program.
Clinically significant abnormalities on oral or physical examination, medical history, ECG, vital signs, or laboratory values at screening or admission to the treatment session, as judged by the investigator or designee.
Any known or suspected history (including family history) of schizophrenia or other psychotic illness. Presence or history of an organic brain disorder or seizure disorder deemed clinically significant by the investigator.
History or presence of clinically significant pulmonary, hepatic, renal, haematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition, which in the opinion of the investigator would have jeopardised the safety of the subject or the validity of the study results.
Known cardiovascular condition or history of a cardiovascular condition at screening.

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
Placebo spray and oral moxifloxacin placebo24 or 36 placebo sprays (12 or 18 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin placebo on Day 5.	Drug	High dose placebo and oral moxifloxacin placebo
Sativex spray and oral moxifloxacin placebo8 Sativex sprays (4 sprays twice daily every 12 hours) + 16 or 28 placebo sprays (8 or 14 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin placebo on Day 5.	Drug	Low dose Sativex and oral moxifloxacin placebo
Sativex spray and oral moxifloxacin placebo24 or 36 Sativex sprays (12 or 18 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin placebo on Day 5.	Drug	High dose Sativex and oral moxifloxacin placebo
Placebo spray and moxifloxacin24 or 36 placebo sprays (12 or 18 sprays twice daily every 12 hours) for 5 days and single oral moxifloxacin 400 mg tablet on Day 5.	Drug	High dose placebo and single oral moxifloxacin 400 mg tablet

Primary outcome

Time-matched change from baseline in QTc based on an individual correction (QTcl)
Time frame: 5 days

14 secondary outcomes

QTc with Fridericia correction method (QTcF) and the QTc with Bazett correction (QTcB)
Time frame: 5 days
Heart Rate
Time frame: 5 days
PR interval
Time frame: 5 days
QRS interval
Time frame: 5 days
Uncorrected QT interval
Time frame: 5 days
Change in ECG morphological patterns
Time frame: 5 days
Correlation between the QTcl change from baseline and plasma concentrations of the parent metabolites
Time frame: 5 days
Adverse Events
Time frame: Up to 2 weeks after final dose
Clinical laboratory parameters
Time frame: Up to 2 weeeks after final dose
Vital signs
Time frame: Up to 2 weeks after final dose
Oral and physical examination
Time frame: Up to 2 weeks after final dose
Peak plasma concentration (Cmax)
Time frame: Days 5 and 6
Time to peak plasma concentration (Tmax)
Time frame: Days 5 and 6
Area under the concentration curve (AUC(0-t) and AUC(0-inf))
Time frame: Days 5 and 6

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 27121791Sellers EM, Schoedel K, Bartlett C, Romach M, Russo EB, Stott CG, Wright S, White L, Duncombe P, Chen CF. A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray. Clin Pharmacol Drug Dev. 2013 Jul;2(3):285-94. doi: 10.1002/cpdd.36. Epub 2013 May 14.

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?

A Phase 1 study of Effects of Sativex on ECG, run by Jazz Pharmaceuticals at 1 site in Canada.

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 24 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 Canada. 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. Some participants in this study may receive a placebo. 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?

Time-matched change from baseline in QTc based on an individual correction (QTcl) (time frame: 5 days). 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 NCT01322139, 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 27 Oct 2026.