To determine the safety, tolerability and pharmacokinetics (PK) of LY3154207 in a SAD study in healthy volunteers

This was a phase 1, SAD, crossover design of LY3154207 in healthy subjects conducted in 2 alternating cohorts with dose escalation. Subjects were dosed at 25 mg, 75 mg, 100 mg, 150 mg and 200 mg or placebo. Safety parameters assessed included adverse events (AEs), safety laboratories, vital signs, ambulatory blood pressure monitoring (ABPM) and electrocardiogram (ECG).  Subjects provided blood samples after dosing to measure plasma concentrations of LY3154207 for assessment of PK.

Eighteen subjects enrolled with 17 subjects completing the study. Subjects had a mean age (SD) of 33.6 (13.0), 16 were male (89%) and 16 white (89%). One subject withdrew due to anxiety following a 150 mg dose.  A total of 111 treatment emergent AEs occurred and were mostly mild (101/111).  Insomnia, decreased appetite, anxiety, dizziness, headache, nausea, upper abdominal pain, and dysgeusia were the most common AEs and the majority (69/111) occurred at doses ≥100 mg. A dose-related signal for increases in pulse and blood pressure occurred and resolved in 24 hours. The Cmax and AUC was proportional with dose administered.  The median tmax and the t1/2 were approximately 2-3 and 12 hours, respectively.   The administered LY3154207 dose excreted in urine was 0.02%.