An Open Label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics and Tolerability of a Single Oromucosal Dose of 4 Sprays of Sativex(Containing 10.8 mg Delta-9-tetrahydrocannabinol [THC] and 10 mg Cannabidiol [CBD]) in Patients With Impaired Hepatic Function and Healthy Subjects With Normal Hepatic Function.

Exclusion criteria

• Donation or loss of 400 mL or more of blood within eight weeks prior to dosing.
• Significant concomitant illness within the two weeks prior to dosing.
• Resting heart rate \<40 bpm.
• History of autonomic dysfunction.
• History of clinically significant drug allergy; a known hypersensitivity to the study drug or drugs similar to the study drug.
• Any surgical or medical condition (other than hepatic impairment) which might significantly alter the absorption, distribution, metabolism or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
• Any history of significant bleeding and haemorrhagic tendencies. However, subjects with a history of bleeding tendencies secondary to hepatic impairment will be excluded based on Principal Investigators' discretion.
• History of immunocompromisation, including known history of human immunodeficiency virus seropositivity.
• History of drug abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
• Unwilling to abstain from alcohol during this study.
• Currently receiving a prohibited or restricted medication and unwilling to stop or comply with restriction for 14 days prior to the screening visit and for the duration of the study.
• 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 and unwilling to abstain for the duration of the study.
• A known or suspected history or family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with underlying condition.
• A history of uncontrolled epilepsy as evidenced by one or more seizures in the last 12 months.
• Significant cardiac disease, e.g. has experienced myocardial infarction (MI) (if the screening ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the subject can enter the study at the discretion of the Investigator and/or local medical monitor) or clinically relevant cardiac dysfunction within the last six months, or any of the following within the last six months:
• had a coronary artery bypass surgery or percutaneous coronary intervention,
• has unstable angina or has had stroke,
• unstable heart insufficiency (New York Heart Association grade III-IV),
• has a cardiac disorder that, in the opinion of the Investigator, would put the subject at risk of a clinically relevant arrhythmia or MI, or has a secondary or tertiary atrioventricular block.
• Had liver surgery (including transplantation) within the last six months.
• Has significant renal disease or significantly impaired renal function with a creatinine clearance below 50 mL/min for Group 1 and 2, or below 40 mL/min for Group 3.
• 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 effective contraception, for example, oral contraception, double barrier or intra-uterine device, during the study and for three months thereafter (however, a male condom should not be used in conjunction with a female condom as this may not prove effective).
• Female subject who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
• Any clinically significant abnormal findings in physical or oral examination, ECG or laboratory evaluations (not consistent with known clinical disease) which, 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.
• Subjects who are unwilling to abstain from smoking from midnight on Day -1 to four hours post dose Day 1.
• Subjects who consume more than five caffeinated beverages per day (e.g. 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 the period of in-patient confinement.
• Unwilling to abstain from donation of blood during the study.
• Travel outside the country of residence planned during the study.
• Subjects previously enrolled into this study.
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal product (IMP).
• Subjects who have received an IMP within 30 days or five times the half-life of the IMP (whichever is greater) prior to the screening visit. Groups 1, 2, and 3 (hepatic impairment)
• Symptoms or history of Stage III or worse degree of encephalopathy.
• Clinical evidence of severe ascites.
• Any evidence of acute progressive liver disease.
• Patients with clinically abnormal prothrombin time will be excluded based on the Principal Investigators' discretion. Group 4 (healthy controls)
• A positive Hepatitis B surface antigen or Hepatitis C test result.
• History of alcohol abuse within the 12 months prior to dosing or evidence of such abuse, as indicated by the laboratory assays conducted during the screening or baseline evaluations.
• Use of any prescription medication within 14 days prior to dosing except for hormonal contraceptives.
• Use of over-the-counter medications or vitamins within 14 days prior to dosing (except for the occasional use of paracetamol).