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

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:
• •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.