Buprenorphine Dose Escalation Trial for Treatment of Non-Dependent Opiate Users - 2

This will be an open-label, single dose-escalation trial. A total of 24 opiate experienced, but not dependent subjects will receive four ascending doses of buprenorphine, 4, 8, 16, and 24 mg, respectively, with an at least a 14 day washout interval between treatments. The four treatments are sublingual administration of:

• two 2-mg buprenorphine sublingual tablets,
• one 8-mg buprenorphine sublingual tablet,
• two 8-mg buprenorphine sublingual tablets; and
• three 8-mg buprenorphine sublingual tablets.

The dose proportionality in plasma profiles of buprenorphine and dose response of the buprenorphine sublingual tablets are evaluated at buprenorphine dose range of 4 to 24 mg.

Inclusion criteria

• Be male or female of any race, between 21 and 45 years of age.
• Weigh within 15% of ideal body weight for height according to the current life insurance table.
• Be in good physical and mental health as judged by interview and physical examination.
• Have no significant oral cavity pathology including excessive caries, gingivitis, infectious or inflammatory disease, or recent piercing of the oral cavity.
• Be experienced in illicit use of opiates but not be physically dependent on opiates and other drugs (except nicotine or caffeine) at the time of the study. A history of other psychoactive drug use is acceptable but preference will be for subjects reporting less frequent and more controlled illicit drug use.
• For female subjects, test nonpregnant and use adequate birth control, and not be lactating.
• Be capable of providing written informed consent to participate in this study.
• Be able to comply with protocol requirements and be likely to complete all four study treatments.

Exclusion criteria

• Have a diagnosis of drug addiction (other than nicotine, caffeine, and opiate) as per DSM-IV criteria.
• Have any significant, active medical or psychiatric illnesses (other than drug dependence) which might inhibit their ability to complete the study or might be complicated by administration of study medications.
• Have clinically significant abnormal laboratory measurements in liver function tests (AST and ALT levels greater than 3 times the upper limit of normal), hematology (CBC, differential, platelet count), serum chemistries (SMA-24) and urinalysis at screening.
• Test positive on the HIV blood screen.
• Have a history of significant hepatic, renal, endocrine, cardiac, nervous, psychiatric, gastrointestinal, pulmonary, hematologic or metabolic disorders.
• Have known hypersensitivity to buprenorphine and its derivatives or opiates or opiate-like analgesics.
• Receive any medications for medical conditions.
• Have any condition or history considered by the investigator(s) to place the subjects at increased risk.
• Do not actively meet the inclusion criteria at the time of screening.