Sr. Clinical Pharmacologist AbbVie Mount Prospect, Illinois, United States
Background: ABBV-552 is an agonist of synaptic vesicle glycoprotein 2A (SV2A) which is currently being investigated for use in cognitive deficiencies related to Alzheimer’s disease. This phase 1, multicenter, open label, parallel cohort study was conducted to study the pharmacokinetics (PK), safety, and tolerability of ABBV-552 in healthy adult Japanese and Han Chinese subjects, and to compare PK and safety with healthy adult Western subjects from previous studies. Methods: Healthy adult Japanese subjects in Cohort 1 received single ascending oral doses of 5 mg, 15 mg, and 40 mg ABBV-552 with a washout of 7 days between each period. Healthy adult Han Chinese subjects in Cohort 2 received a single oral dose of 40 mg ABBV-552. Plasma PK samples were collected at pre-dose, and at various intervals up to 144-hours post dose for both cohorts. Safety assessments included vital signs, adverse event (AE) monitoring, 12-lead ECG measurements and clinical laboratory analysis. Results: All subjects completed the study and were included in the safety analysis. Cmax and AUC increased dose-proportionally in Japanese subjects. Healthy adult Japanese and Han Chinese subjects had comparable Tmax and Cmax. The mean AUC value for Han Chinese subjects was approximately 20% higher than that for Japanese subjects. Individual concentration-time profiles following administration of a 40-mg dose were similar between the 2 cohorts and with historical data from healthy adult Western subjects.
Single doses of ABBV-552 was were safe and tolerable at all tested doses. The most common AEs reported by >2 subjects were dizziness (39%), and somnolence, fatigue, and papule (11% each). All AEs were Grade 1 (61%) or Grade 2 (11%) and resolved. There were no serious AEs. No unique safety signals were observed compared to Western subjects, and there were no clinically significant laboratory or ECG findings. Elevated liver enzymes were not clinically significant and normalized on follow-up. Conclusion: ABBV-552 PK and tolerability in healthy adult Japanese and Han Chinese subjects are comparable to that observed in healthy adult Western subjects in previous clinical studies. The results of this study support the inclusion of Asian patients in the currently enrolling global phase 2 Alzheimer’s disease trial.
