NMDA Receptor Modulation for Hyperarousal in PTSD

This study aims to provide a rigorous test of functional target engagement and "go/no go"
milestones for a subsequent POC trial. Investigator will conduct a parallel-arm, randomized,
double-blind, placebo-controlled study to assess lanicemine (100 mg) with respect to a
functional pharmacodynamic readout of target engagement (APS). Twenty-four patients with
significant PTSD symptoms and elevated APS will be randomized to one of 2 treatment groups
[placebo or 100 mg], and undergo three 60 min parenteral infusions over a 5 day period. APS
and other neurophysiological biomarkers will be tested before and after the 1st and 3rd
treatment.

Primary Objective is to examine, relative to placebo, whether lanicemine will demonstrate
normalization of the APS response following three treatments.

Secondary Objectives are to examine, relative to placebo, whether lanicemine will demonstrate
effects on P50 auditory evoked potentials, gamma band EEG, and Mismatch Negativity.
Investigator also explore whether target engagement will mediate the effect of treatment on
CAPS-5 scores.

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Patients must provide acceptable proof of identity documentation to confirm initials
and date of birth

3. Male and female patients aged 21 to 65 years, inclusive.

4. All male patients who are sexually active must agree to use a double barrier method of
contraception (condom with spermicide) from the first dose of IP until 12 weeks after
their last dose. All females must have a negative serum pregnancy test. Women of
childbearing potential (WOCBP, see below) must use a highly effective form of birth
control plus the use of a condom by the male sexual partner, reviewed and approved by
the PI. The highly effective form of birth control includes: true sexual abstinence, a
vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any
effective IUD/IUS, Depo-Provera injections, oral contraceptive, and Evra Patch or
Nuvaring. Women should be on a stable method of birth control for a minimum of 3
months , prior to randomization and 3 months after the last dose of IP.

Women of non-childbearing potential. Women of non-childbearing potential are defined
as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy,
or bilateral salpingectomy), or who are postmenopausal. Women will be considered
postmenopausal if they are amenorrheic for 12 months prior to randomization without an
alternative medical cause. The following age-specific requirements apply:

Women < 50 years old would be considered postmenopausal if they have been amenorrheic
for 12 months or more following cessation of exogenous hormonal treatment and follicle
stimulating hormone (FSH) levels in the postmenopausal range.

Women ≥ 50 years old would be considered postmenopausal if they have been amenorrheic
for 12 months or more following cessation of all exogenous hormonal treatment.

5. CAPS-5 score ≥ 25 and CGI-S ≥ 4 at Screening and Randomization

6. Anxiety Potentiated Startle T-score ≥ 2.8.

7. Psychotropic medications must remain at a stable dose for at least 42 days prior to
screening, without clinically significant adjustment.

8. Be able to understand and comply with the requirements of the study, as judged by the
investigator

Exclusion Criteria:

1. Patients who are currently participating in another clinical study in which the
patient is exposed to an investigational or non-investigational drug or device, or
have done so within the last 30 days prior to screening.

2. Patients who have no regular contact with an adult who could come to the patient's aid
should an urgent need arise.

3. Patients with a history of DSM-5 diagnosis of bipolar disorder, schizophrenia or
schizoaffective disorder, or currently exhibiting psychotic symptoms associated with
depression; dementia or suspicion thereof, is also exclusionary.

4. Currently being treated with MAOIs, lithium, divalproex, carbamazepine, barbiturates,
or benzodiazepines. Patients taking medications with known activity at the NMDA or
AMPA glutamate receptor [eg, riluzole, amantadine, lamotrigine, memantine, topiramate,
dextromethorphan, D-cycloserine], or the mu-opioid receptor.

5. Patients who meet DSM-5 criteria for substance use disorder (amphetamines, cocaine,
hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics) within 1 month
prior to screening. Patients with a positive urine drug screen (UDS) are excluded
except for patients testing positive for prescribed medications that are otherwise
permitted and there is no evidence of misuse or abuse. Patients can be re-tested only
if either the initial opiate or barbiturate result is positive and they have a
prescription, but the patient should be excluded if the result is still positive at
the second test. Patients with positive UDS for drug(s) legally available by
prescription must provide evidence of prescription for the drug(s).

6. Patients with a binge-pattern of alcohol use which makes them at risk for
withdrawal-related seizures. Also, significant alcohol withdrawal symptoms that
require medical detoxification.

7. Patients with a suicide attempt within the last 3 months or at imminent risk of
suicide and not suitable for an outpatient study, in the judgment of the investigator.

8. Patients who are pregnant or lactating.

9. Clinically significant laboratory value, physical examination, or ECG that signifies a
major medical illness that is unstable or inadequately controlled, or that may put the
subject at risk during the study in the judgment of the investigator. Hypothyroidism
is permitted if corrected and the patient is on a stable treatment regimen for a
minimum of 6 months.

10. Systolic BP < 85 or > 160 mmHg or diastolic BP > 100 mmHg or heart rate < 50 or >105
beats per minute at Screening or Randomization. Exclusionary values may be repeated
once.

11. QTcF (Fridericia-corrected) ≥ 450 msec at Screening or Randomization. Exclusionary
values may be repeated once.

12. Patients with any history of seizure disorder (except for febrile seizures in
childhood) or traumatic brain injury.

13. Previous exposure to lanicemine.

14. Patients with a personality disorder which in the opinion of the investigator has a
major impact on the patient's current psychiatric status and would preclude safe study
participation.

15. Body mass index (BMI) ≥ 40 kg/m2