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

Study Overview
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Brief Summary
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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
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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

Official Title
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A Two-part Study: Part 1 is a Multiple-dose (7-day), Open-label Evaluation of the Safety, Tolerability, and Pharmacokinetics of HT-2157 in Healthy Subjects. 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

Conditions
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Healthy Volunteers (Part 1), Major Depressive Disorder (Part 2)

Intervention / Treatment
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* Drug: HT-2157
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HT-2157<br> | Drug: HT-2157<br>* QD oral dosing<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* QD oral dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day plasma PK profile of HT-2157 | 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 | 7-day | 
| To assess the brain penetration of HT-2157 | To assess the brain penetration (PK [including Cmax, Tmax, AUC if possible] in cerebrospinal fluid [CSF]) of HT-2157 (and its metabolite) | 21-days | 
| 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 | 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 | 21-days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of multiple (7-day) doses of HT-2157 | 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. | 7-days | 
| Safety and tolerability of multiple (21-day) ascending-doses of HT 2157 | 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-days | 
| 21-day ascending-dose plasma PK profile of HT-2157 | 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 | 21-days |