Format

Send to

Choose Destination
Clin Drug Investig. 2018 May;38(5):401-415. doi: 10.1007/s40261-018-0618-4.

Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.

Author information

1
Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad, 500034, India. nvsrk@suven.com.
2
Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad, 500034, India.

Abstract

BACKGROUND AND OBJECTIVE:

SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease. The objective of this study was to characterize the safety, tolerability and pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects following single and multiple oral doses.

METHODS:

Single doses (5, 15, 50, 100 and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100 mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose) was evaluated using an open-label, two-period, randomized, fed and fasted in a crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored using validated analytical methods.

RESULTS:

SUVN-502 is safe and well tolerated up to the highest tested single dose of 200 mg in healthy young adults and multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more than dose-proportional over the evaluated dose range. Food and gender did not have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total (AUC0-∞, and AUC0-last) and peak exposures (Cmax) were 2.9- and 2.2-fold higher, respectively, in elderly subjects compared to young subjects. Steady-state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of SUVN-502.

CONCLUSIONS:

SUVN-502 exhibited an acceptable safety, tolerability and pharmacokinetic profile in healthy young adults and elderly subjects. Based on the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to Phase 2 evaluation in patients with moderate AD.

PMID:
29380267
DOI:
10.1007/s40261-018-0618-4
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center