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

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

Main Inclusion Criteria (Part 1)

• No clinically relevant abnormalities
• Age 18 to 55 years, inclusive
• Body Mass Index (BMI) of 18.5 to 32 kg/m2

Main Inclusion Criteria (Part 2)

• No clinically relevant abnormalities
• Age 18 to 55 years, inclusive
• Body Mass Index (BMI) of 18.5 to 32 kg/m2
• Mild-to-Moderate major depressive disorder

Main Exclusion Criteria (Part 1)

- Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs

Main Exclusion Criteria (Part 2)

• Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs
• Current and primary Axis I disorder other than MDD