The purpose of this study is to measure the amount of ketamine in blood over time in subjects diagnosed with Major Depressive Disorder (MDD) and explore the anti-depressive effects of ketamine delivered by transdermal patch.

SHX-C301 is a Phase 1, first in human, single-blind, multi-center clinical study to evaluate the pharmacokinetics (PK), safety and antidepressant effects of SHX-001 transdermal patch low dose delivered based on prediction and high dose delivered based on the estimation from the low dose PK in subjects with MDD and sub-optimally controlled by standard of care.

Inclusion Criteria:

• Present a current depressive episode of at least 8 weeks
• Have a body mass index (BMI) of 18-35 kg/m2 (inclusive) at screening
• Agree to use adequate methods of contraception during the study (and for X days after discharge)

Exclusion Criteria:

• A history of alcohol consumption exceeding 14 drinks/week within the 5 years before study entry.
• Use of prescription or non-prescription drugs, vitamins, or dietary supplements within 14 days prior to the first dose of study medication except ongoing stable dose of antidepressant.
• Treatment with any investigational drug, use of any known CYP3A4 enzyme-inducing/inhibiting agents (e.g., barbiturates, phenothiazines, cimetidine, St. John's Wort) or herbal supplements within 7 days prior to the first dose of study medication
• A history of drug abuse or dependence within 180 days of screening
• A febrile illness within 5 days prior to the first dose of study medication.
• A known hypersensitivity to ketamine
• A history of use ketamine for Major Depressive Disorder and did not respond to ketamine
• Recent use of ketamine in any formulation for any indication (within 4 weeks prior to screening)