A Multiple Ascending Oral Dose Evaluation of the Safety, Tolerability, and Pharmacokinetics of DSP-1053 and Its Metabolites in Healthy Subjects and in Subjects With Major Depressive Disorder

This study will be conducted at a single site as a double-blind, placebo-controlled,
mulitple ascending oral doses evaluation of the safety, tolerability, and pharmacokinetics
of DSP-1053 and its metabolites in healthy subjects with Major depressive disorder after the
minimumally intolerated dose is reached in healthy subjects

Inclusion Criteria:

Healthy Subjects:

Be able to understand and willing to sign the Informed Consent Form, and capable of
providing written authorization for use and disclosure of protected health information per
requirements of 45 Code of Federal Regulations (CFR) 164.508 (Health Information
Portability and Accountability Act [HIPAA]).

Be healthy male or female subjects between 18 and 50 years of age (inclusive). Have a BMI
18 and 33 kg/m2. Have no clinically relevant abnormal laboratory values at screening and
Day -1.

Have no clinically relevant findings from vital sign measurements at screening and
check-in.

Have no clinically relevant findings from physical examination at screening and check in.

Have a negative urine drug of abuse test (cannabinoids, barbiturates, cocaine, opiates,
benzodiazepines, phencyclidine, and methadone) and negative cotinine test at screening and
check in.

Have a negative alcohol breath test at screening and check in. Have a negative Hepatitis B
surface antigen, Hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
tests at screening.

Have normal hepatic function [aspartate transaminase (AST), bilirubin, and alanine
transaminase (ALT)] and renal function (creatinine clearance greater than 80 mL/min as
assessed by Cockcroft Gault equation using serum creatinine) at screening and Day 1.

Be females who are of childbearing potential:

have a negative serum hCG pregnancy test at screening and Day -1; willing to not
breastfeed from Day -5 until 90 days after discharge from the study site;

Be females who are:

unable to have children (eg, post menopausal, tubal ligation, hysterectomy) OR willing to
remain abstinent (not engage in sexual intercourse) from check in until 90 days after
discharge from the study site.

OR willing to use an effective method of double-barrier birth control (eg, partner using
condom and female using diaphragm, contraceptive sponge, spermicide, or intrauterine
device) from check-in until 90 days after discharge from the study site.

Be males who:

are sterile or willing to remain sexually abstinent or use an effective method of birth
control (eg, condom) from check-in until 90 days after discharge from the study site.

AND agree not to donate sperm during the study and for 90 days after discharge from the
study site.

Refrain from strenuous physical activity from 48 hours prior to check-in until discharge
from the study site.

Agree to remain housed at the study site for the clinical confinement of study and return
for any visits required for additional safety or PK assessments.

Agree to consume study meals per protocol.

Subjects with MDD:

In addition to inclusion criteria mentioned above for healthy subjects, the following
inclusion criteria will be applied to subjects with MDD:

Have the diagnosis of MDD as defined by the Diagnostic and Statistical Manual of Mental
Disorders Fourth Edition; Text Revision (DSM IV TR) criteria and confirmed by the Mini
International Neuropsychiatric Interview (MINI) diagnostic interview. This diagnosis will
be confirmed by a psychiatrist or psychologist. The diagnosis should be supplemented (when
possible) by confirmation of chart records or by a discussion with a treating healthcare
professional or reliable informant. Diagnosis made by a psychologist must be reviewed by a
psychiatrist.

The subjects' current major depressive episode must be ≥ 4 weeks and < 2 years in
duration.

Are able to wash-out from prior antidepressant therapies by Day -1, are able to forego
psychotherapy from Day -1 through Day 10, inclusive, and are deemed clinically stable by
PI's assessment.

May have a comorbid anxiety disorder such as generalized anxiety disorder (GAD) or social
phobia but not obsessive compulsive disorder (OCD) as long as the comorbid anxiety
disorder is not the major source of impairment.

Have a stable living arrangement for at least 3 months prior to check in and agree to
return to a similar living arrangement after discharge. This criterion is not meant to
exclude subjects who have temporarily left a stable living environment. Such subjects
remain eligible to participate in this study. Chronically homeless subjects should not be
enrolled. The Medical Monitor should be consulted for individual cases as needed.

Exclusion Criteria:

Healthy Subjects

Significant history or clinical manifestations of any acute or chronic condition that in
the opinion of the PI, would limit the subject's ability to complete and/or participate in
the study:

metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal,
urological, neurological, or psychiatric disorders; drug hypersensitivity; stomach or
intestinal surgery or resection that would potentially alter absorption and/or excretion
of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be
allowed at the discretion of the PI); abnormal ECG, which, in the PI's opinion, is
clinically significant; known or suspected alcohol or substance abuse/ dependence within
one year prior to check in; movement disorders including tremor; lifetime or family
history of seizures or a febrile seizure. Poor peripheral venous access. Does not tolerate
venipuncture. Donation of blood from 28 days prior to screening through study completion,
inclusive.

Receipt of blood products within 2 months prior to check in. Any acute or chronic
condition that, in the opinion of the PI, would limit the subject's ability to complete
and/or participate in this clinical study.

Female subjects with menstrual dysfunction. Considered by the PI to be at imminent risk of
suicide or injury to self, others, or property.

Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the CSSRS at screening.

Subjects who, by history, have smoked or used tobacco products within 60 days from
screening until study follow up.

Consumption of food or beverages containing alcohol, grapefruit, or caffeine within 72
hours prior to check in and until discharge from the study site, unless deemed acceptable
by the PI.

Participation in any other investigational study drug trial in which receipt of an
investigational study drug occurred within 5 half lives or 3 months prior to check-in,
whichever is longer.

Taken any drug(s) known to be clinically relevant cytochrome P450 2D6 (CYP2D6), or
cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 28 days prior to the first DSP
1053 dose and during the study conduct through follow up.

Taken any antihistamines within 14 days prior to check-in and during the study. Family
history of prolonged QT interval (QTc) prolongation. Subjects, who by history, are at any
risk for bleeding or have abnormal prothrombin values or currently use of anticoagulant
treatment (such as warfarin) Clinically important folic acid or B12 abnormalities detected
within 3 months before screening.

Use of any prescription medications/products within 14 days prior to check in unless
deemed acceptable by the PI.

Subjects with MDD

Except for Exclusion Criterion 18 mentioned above for healthy subjects all exclusion
criteria will be applied and in addition the following exclusion criteria will be applied
to subjects with MDD:

History of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, eating
disorder, or obsessive compulsive disorder.

Any current Axis I disorder other than major depressive disorder which is the focus of
treatment.

Substance or alcohol abuse in the last 3 months or substance or alcohol dependence in the
last 12 months.

Concomitant psychotropic medication, including herbals. Significant risk of violent
behavior or a significant risk of suicidal behavior based on history or in the PI's
judgment.