Pharmacokinetics - Pharmacodynamic Study of HT-2157 in Healthy Subjects and in Patients With Major Depressive Disorder

Phase 1

Completed

Brief Summary: This is a two part study. The objective of Part 1 is to evaluate the safety, tolerability, and pharmacokinetics of HT-2157 in healthy normal volunteers

Part 2 is a randomized, double-blind, placebo-controlled, multiple (21-day) ascending-dose evaluation of the safety, tolerability, pharmacokinetics, and pharmacodynamics of HT-2157 in patients with major depressive disorder

Detailed Description: This is a two part study. The objective of Part 1 is to evaluate the safety, tolerability, and pharmacokinetics of HT-2157 administered for 7-days in healthy normal volunteers

Part 2 is a randomized, double-blind, placebo-controlled, multiple ascending-dose evaluation of the safety, tolerability, pharmacokinetics of HT-2157 administered for 21-days in patients with major depressive disorder. The primary objective of Part 2 is to assess the CNS penetration of HT-2157 in cerebrospinal fluid. In addition, the potential activity of HT-2157 in this patient population may be assessed using exploratory biologic and pharmacodynamic markers of potential efficacy

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
HT-2157	HT-2157	-

Primary Outcome Measures

Name	Time	Method
7-day plasma PK profile of HT-2157	7-day	To assess the multiple dose (7-day) plasma PK profile (including AUC, Cmax, Tmax, T1/2, CL/F, Lambda z, VZ/F) of HT-2157 (and its metabolite) administered in the fed state to healthy male and female subjects
To assess the brain penetration of HT-2157	21-days	To assess the brain penetration (PK \[including Cmax, Tmax, AUC if possible\] in cerebrospinal fluid \[CSF\]) of HT-2157 (and its metabolite)
PD profile (CSF and peripheral biomarkers, exploratory biologic and pharmacodynamic markers of potential efficacy) of multiple (21-day) doses of HT-2157 patients with MDD	21-days	To assess the PD profile (CSF and peripheral biomarkers, exploratory biologic and pharmacodynamic markers of potential efficacy) of multiple (21-day) doses of HT-2157 administered in the fed state to patients with MDD

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of multiple (7-day) doses of HT-2157	7-days	To assess the safety and tolerability of multiple (7-day) doses of HT-2157 administered in the fed state to healthy male and female subjects. Change from baseline will be assessed for the following measures: Vital signs, 12-lead ECG, laboratory (hematology, chemistry, urinalysis), physical examinations, and adverse events.
Safety and tolerability of multiple (21-day) ascending-doses of HT 2157	21-days	To assess the safety and tolerability of multiple (21-day) ascending-doses of HT 2157 administered in the fed state to patients with MDD. Change from baseline will be assessed for the following measures: Vital signs, 12-lead ECG, laboratory (hematology, chemistry, urinalysis), physical examinations, and adverse events.
21-day ascending-dose plasma PK profile of HT-2157	21-days	To assess the multiple (21-day) ascending-dose plasma PK profile (including AUC, Cmax, Tmax, T1/2, CL/F, Lambda z, VZ/F, RaCmax, RaAUC) of HT-2157 (and its metabolite) administered in the fed state to patients with MDD