An Study to Evaluate the Effects of Fluconazole on the Pharmacokinetics (PK) of Sativex® in Healthy Subjects With Cannabis Experience.

This is a Phase I, open-label, randomized, single-dose, two-sequence, two-treatment,
four-period, crossover study to evaluate the effects of fluconazole on the PK of Sativex® in
healthy subjects with cannabis experience.

Subjects will be randomly assigned to one of the two treatment sequences. Each sequence has
four Inpatient Periods. During each Inpatient Period, a subject will either receive a single
dose of Sativex® alone (Treatment A) or a single-dose Sativex® coadministered with the
interaction drug, fluconazole (Treatment B). The crossover treatments will be separated by a
washout period of at least 10 days, but no more than 12 days, between each Sativex® dose.

Specifically in both Treatments A and B, a single oromucosal dose of Sativex® (10.8 mg THC
and 10 mg CBD delivered in four sprays) will be administered in a fasted state on Day 1
within each Inpatient Period. During Treatment B, fluconazole 200 mg twice daily (BID) for
two days, will be administered at the following time points relative to the Day 1 Sativex®
dose: 1 hour pre-dose, and approximately 11, 24, and 36 hours post-dose.

Subjects will be checking into the clinical research facility on Day 1 for each Inpatient
Period. Subjects will be confined to the clinical research facility during each Inpatient
Period, remaining in the clinical unit after dosing under observation through the collection
of all PK blood samples. Fifteen PK blood samples will be taken per subject during each
study period: prior to Sativex® dosing (t=0) and at the following multiple time points after
dosing: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours; along with some
select samples for fluconazole measurements (Day 1 and 2 pre-fluconazole morning dose, 4
hours and 8 hours post-fluconazole morning dose). Subjects will be discharged from the unit
after the 48-hour post-dose PK sample and samples for clinical laboratory tests and vital
signs have been taken and the subject is determined to be fit for discharge.

A Safety Follow-Up Visit will be performed 7 (+2) days after last Inpatient period.

The expected duration for study participation (including Screening Visit, Inpatient Periods,
and Safety Follow-up Visit) for each individual subject is a maximum of 61 days.

Inclusion Criteria:

For inclusion in the study subjects must fulfill ALL of the following criteria:

1. Willing and able to give written informed consent for participation in the study.

2. Healthy, male or female, between 18 and 45 years of age (inclusive).

3. Previous experience with cannabis; "cannabis experience" is defined as use of
cannabis in the past, but not within 12 months prior to entry into the study.

4. Able (in the investigator's opinion) and willing to comply with all study
requirements.

5. Willing and able to communicate with the investigator.

6. Vital signs at screening (after five minutes resting measured in the supine position)
within the following ranges:

1. Body temperature between 35.0 to 37.5 °C

2. Systolic blood pressure, 90 to 150 mmHg*

3. Diastolic blood pressure, 60 to 90 mmHg*

4. Pulse rate, 40 to 99 beats per minute*. (*Blood pressure and pulse rate will be
taken again in a standing position. After two minutes standing, there shall be
no more than a 20 mmHg drop in systolic or 10 mmHg drop in diastolic blood
pressure, associated with clinical manifestation of postural hypotension).

7. Body mass index (BMI) between 18-30 kg/m2 (both inclusive) as calculated by the
following BMI formula: Weight (kg) ÷ [Height (m)]2

8. Willing for his or her name to be reported to the responsible authorities for
participation in this study, as applicable in individual countries.

9. Willing to allow his or her primary care practitioner and consultant to be notified
of participation in the study.

Exclusion Criteria:

The subject may not enter the study if ANY of the following apply:

1. Donation or loss of 400 mL or more of blood within eight weeks prior to first dosing
(Visit 2) and unwilling to abstain from donation of blood during the study.

2. Significant concomitant illness within the two weeks prior to first dosing (Visit 2).

3. At risk for requiring hospital admission or extended hospital stay during the study
or any scheduled elective hospitalization during the planned study duration.

4. Has any surgical or medical condition, significant disease or disorder or any finding
on physical examination and/or oral examination which might significantly alter the
absorption, distribution, metabolism or excretion of drugs or that, in the opinion of
the investigator, may put the subject at risk, influence the result of the study, or
the subjects' ability to participate in the study.

5. Clinical evidence of acute or chronic liver disease or liver injury as indicated by
clinically significant abnormal liver function tests such as aspartate
aminotransferase, alanine aminotransferase, gamma glutamyl-transpeptidase, alkaline
phosphatase, (any ≥2.5 upper limit of normal [ULN]) or serum bilirubin (≥1.5 ULN)
unless there is another more likely explanation (eg, Gilbert's syndrome).

6. Significant renal disease or significantly impaired renal function with an estimated
creatinine clearance below 50 mL/min.

7. Any known or suspected hypersensitivity to cannabinoids or any of the excipients of
the IMP, Sativex.

8. Have a history of known hypersensitivity or idiosyncratic reaction to fluconazole,
its excipients, or related compounds.

9. Positive result for the presence of hepatitis B surface antigen (HBsAg), hepatitis C
virus antibodies (HCAb), or HIV I or II antibodies.

10. Currently using or has used cannabis and/or cannabinoid based medications (eg,
Marinol®, Nabilone®, Cannador®) or Acomplia (rimonabant) or taranabant within 12
months prior to first dosing (Visit 2) and is unwilling to abstain for the duration
of the study.

11. Currently using or has used an illicit drug or non prescribed use of any prescription
drug within 12 months prior to first dosing (Visit 2) and is unwilling to abstain for
the duration of the study.

12. Any known or suspected history of a substance abuse/dependence disorder within the 12
months prior to first dosing (Visit 2).

13. Has a positive urine drug (including THC) or alcohol result at screening or on Day -1
of Visit 2.

14. Current heavy alcohol consumption (more than 60 g of pure alcohol per day for men,
and more than 40 g of pure alcohol per day for women).

15. Unwilling to abstain from drinking alcohol during this study (for 24 hours prior to,
and for the duration of, each study visit).

16. Had any treatment with any known enzyme-altering agents (barbiturates,
phenothiazines, cimetidine, etc.) within 30 days prior to first dosing (Visit 2) or
during the study.

17. Unwilling to abstain from nicotine products from midnight Day -1 to 48 hours postdose
for each Inpatient Period.

18. Unwilling to abstain from grapefruit products for one week prior to and throughout
the Inpatient Period.

19. Have had substantial changes in eating habits, per the investigator's opinion, within
30 days prior to screening.

20. Consume more than five caffeinated beverages per day (eg, five cups of tea or coffee
or cans of cola) or who are unwilling to abstain from consumption of
caffeine-containing food and beverages throughout each Inpatient Period.

21. Any known or suspected history or immediate family history of schizophrenia, or other
psychotic illness, history of severe personality disorder or other severe significant
psychiatric disorder other than depression associated with underlying condition.

22. Any history of epilepsy as evidenced by one or more seizures in the last 12 months.

23. Significant cardiac disease, or a cardiac disorder that in the opinion of the
investigator would put the subject at risk of a clinically relevant arrhythmia or
myocardial infarction, or has a secondary or tertiary atrioventricular block, or
evidence of clinically significant cardiac disease on ECG at screening.

24. Sexually active males whose partner is of childbearing potential who do not agree to
practice two highly effective methods of birth control or remain abstinent during the
study and for three months after the last dose of IMP. Sexually active females of
childbearing potential who do not agree to practice two highly effective methods of
birth control or remain abstinent during the study and for three months after the
last dose of IMP. If employing birth control, two of the following precautions must
be used: established use of oral, transdermal, injected or implanted hormonal methods
of contraception; placement of an intrauterine device or intrauterine system
(consideration should be given to the type of device or system being used, as there
are higher failure rates quoted for certain types, eg, steel or copper wire); Condoms
with spermicidal foam/ gel/ film/ cream/ suppository; the use of a condom should
always be supplemented with the use of a spermicide. Male sterilization (with the
appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
True abstinence: when this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation
methods) and withdrawal are not acceptable methods of contraception.

Note: Non-childbearing potential is defined as female subjects who are surgically
sterile (ie, have undergone bilateral salpingo-oophorectomy, hysterectomy) and female
subjects who have been postmenopausal for at least 12 consecutive months.

25. Pregnant, lactating or planning pregnancy during the course of the study and for
three months thereafter.

26. Received an IMP within 30 days or five times the t½ of the IMP (whichever is greater)
prior to the Screening Visit.

27. Travel outside the country of residence planned during the study.

28. Use of any prescription medication or over-the-counter medication within 14 days
prior to Screening or during the study.

29. Previously enrolled in this study or another Sativex study.