Safety, Tolerability, and Pharmacokinetics of Modified and Immediate Release Anatabine Citrate Formulations

3-Part Study With 2 6-Period Single Dose Parts (Pt 1, Pt 2 Optional) Followed by a 1-Period Multiple Dose Part (Pt 3) to Evaluate Prototype Modified Release Matrix and Multi Particulate Formulations of Anatabine Citrate to Determine PK

Parts 1 and 2:

Subjects take 1 dose of various formulations of the study product, and provide samples for pharmacokinetic (PK) analysis after each, with at least 7 days between doses.

Part 3:

Subjects take 2-4 doses of study product or placebo for 6 days, plus 1 additional dose, and provides samples for PK analysis.

Parts 1 and 2:

Subjects will be admitted to the clinic on the day before dosing (Day -1). Subjects will fast overnight and receive the study product in the morning of Day 1 in a non-randomized manner. Subjects will remain onsite until 24 h post-dose and will return to the clinical unit at 36 and 48 h post-dose to provide a sample for PK analysis.

There will be at least a 7-day washout between regimens. Subject will be telephoned 3-5 days after the final dose to ensure his/her ongoing well-being.

Part 3:

Subjects will be admitted to the clinic on the day before dosing (Day -1). Subjects will fast overnight (for Day 1 and Day 7) and receive the study product or placebo on a once, twice, or three times a day regimen in a randomized, double-blind manner. Subjects will remain onsite until 24 h after the final dose (Day 7), leaving the clinic on the morning of Day 8 and returning at 36 and 48 h post last-dose to provide a sample for PK analysis.

Subject will be telephoned 3-5 days after the final dose to ensure his/her ongoing well-being.

Inclusion Criteria:

• negative for urinary cotinine
• normal test values for liver function
• provide informed consent

Exclusion Criteria:

• clinically significant abnormal biochemistry, hematology, or urinalysis, as judged by the investigator