A phase I study to determine the tolerability and safety of transdermally delivered oxycodone in combination with the novel penetration enhancer tocopheryl phosphate mix (TPM).

Exclusion Criteria1

• History or evidence of drug and/or alcohol abuse; smokers; use of central nervous system (CNS) depressants, other opioids, sedative/hypnotics, phenothiazines, tranquillisers, skeletal muscle relaxants or sedating antihistamines; use of macrolide antibiotics (e.g., Erythromycin), azole antifungal agents (e.g., Ketoconazole) or protease inhibitors (e.g., Ritanovir) within 30 days of study dosing; Evidence of clinically relevant oral, cardiovascular, haematological, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric or skin disorders; History of epilepsy, coronary disease, peripheral vascular diseases, cerebrovascular accident, transient ischaemic attack; uncontrolled hypertension or signs/symptoms of ischaemic heart disease; Any pre-existing medical conditions predisposing the subject to hypoventilation or hypoxaemia; Known allergy or hypersensitivity reactions to naltrexone or to oxycodone, or other opioid analgesics (codeine, fentanyl, hydrocodone, morphine etc.), or allergy to any contents of the gel (i.e., disodium tocopheryl phosphate (TP), sodium di-tocopheryl phosphate (T2P), pemulen gel, triethanolamine, methylparaben); Known allergy or hypersensitivity to lidocaine or Tegaderm(registered trademark) patches or to topical preparations, such as sunscreens; A calculated creatinine clearance (CL) of < 85ml/min; Positive screening test for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen or Hepatitis C antibody; Have a history of low blood pressure (BP) or severe motion sickness e.g., hypotension where BP is persistently < 90/50 mmHg; Consumption of grapefruit or grapefruit juice within 14 days prior to the first day of study confinement and through to completion of the confinement period.