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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers (Part 1); Major Depressive Disorder (Part 2)
• Intervention / Treatment: Drug: HT-2157; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; QD oral dosing
Experimental: HT-2157	Drug: HT-2157; QD oral dosing

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dart NeuroScience, LLC

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: August 4, 2011
• First Submitted That Met QC Criteria: August 9, 2011
• First Posted (Estimate): August 10, 2011

Study Record Updates

• Last Update Posted (Estimate): December 16, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: HT-2157-107