Ketamine for Major Depressive Disorder

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)