A Study in Patients With Major Depressive Disorder

This is a Phase 2a, placebo-controlled, single-blind study in up to 24 patients with major
depressive disorder (MDD).

Subjects will sign consent form prior to any study related procedure and will complete
screening assessments. Subjects will be randomized to either the treatment group or the
placebo group at a ratio of 1:1.

The study will be conducted in two parts. Titration period On Day 1, subjects will complete
all baseline assessments prior to the 1st dosing.

Pramipexole group: Consenting individuals meeting accession criteria will start pramipexole
2.0mg daily dose (1.0mg twice a day) with ondansetron 16mg daily dose (8mg twice a day).
Pramipexole will be titrated up daily or every two days depends on each patients'
tolerability up to the first intolerable dose (FID) or maximum allowed dose (5 mg/day)
according to titration schedule (Table 1). Once subjects reach their FID, their maximum
allowed dose (MTD) will be defined as 1 mg below their FID.

During titration, subjects will be admitted to the clinic (subjects will be discharged on the
day following their pramipexole FID or Day 8 if subjects reach to 5 mg/day of pramipexole.

Placebo group will take 3 placebo tablets twice a day. Maintenance period During the
maintenance phase, patients will be treated with pramipexole MTD or MAD with ondansetron
16mg/day for the remainder of the 8-week treatment.

Placebo group is taking 3 tablets of placebo twice a day during the trial. Exit visit After
the Week 8 visit, study medications will be discontinued, and subject will return for Exit
visit at Week 9.

After the Exit visit, all subjects will return to their prior treatment for depression or
started on a new therapeutic regimen as medically appropriate.

At study completion (or at other times in accordance with Stopping Rules given below), and
all study participants will return to their pre-admission therapeutic regimen or started on a
new therapeutic regimen as medically appropriate. Higher doses of pramipexole IR may be
tapered off at rates deemed medically appropriate by PI.

In this modified single blind study, efficacy raters will be kept unaware of the
participants' treatment status.

An independent data and safety monitoring board (DSMB) will be appointed to have
responsibility for safeguarding the interests of the trial subjects and assessing the safety
and tolerability of the study treatments during the trial.

Inclusion Criteria:

- Patient Population: Males and females with a diagnosis of major depressive disorder

Inclusion Criteria:

1. Signed an Institutional Review Board (IRB) approved informed consent document
indicating that they understand the purpose of and procedures required by the study
and are willing to participate in the study and comply with all study procedures and
restrictions. Informed consent must be obtained from the patient and/or a designated
representative prior to initiating screening procedures to evaluate eligibility of the
study.

2. Males and females aged 18 and 65 years inclusive.

3. Meet DSM-V R criteria for major depression, single episode or recurrent episode, with
or without melancholia and without psychotic features (296.21, 296.22, 296.23, 296.31,
296.32, or 296.33).

4. Had a total score of > 18 on the HAM-D (17-item version), and a score of > 2 on the
depressed mood item of the HAM-D at the screening visit and at the baseline visit.

5. Patients who are currently not on any antidepressants or, Patients on antidepressants
and agree to the appropriate washout period (certain antidepressants with prolonged
effects (e.g., fluoxetine) may need longer than 2 weeks post-discontinuation to obtain
relatively uncontaminated baseline evaluation).

6. Agreed not to start psychotherapy or behavior therapy during the trial. Patients
currently on these types of therapy for at least 3 months are eligible for the study
and could continue to receive therapy during the trial.

Exclusion Criteria:

1. Women who are pregnant, or lactating; or taking a low-estrogen "mini-pill"
contraceptive.

2. Individuals who are currently taking either study medication (pramipexole and/or
ondansetron).

3. Renal and hepatic dysfunction with:

- Total Bilirubin: >1.5 x UNL

- AST: >2.5 x UNL

- ALT: >2.5 x UNL

- Serum Creatinine: >1.5 x UNL

- Creatinine Clearance: <30 mL/min (calculated by Cockcroft and Gault equation)

4. Hypersensitivity to any component of either study medication.

5. Lifetime history of hypomania/mania, psychotic disorder, dementia and borderline or
antisocial personality disorders.

6. History of a serious suicidal attempt in the past 12 months; presence of serious
suicidal tendencies/potential; modified C-SSRS >4.

7. Positive urine screen for benzodiazepines, cocaine/cocaine metabolites, cannabinoids,
amphetamines, barbiturates, and opiates or history of moderate or severe substance
dependence (drugs or alcohol, DSM-V-R criteria) within the past 6 months of the
screening visit.

8. Non-responders to at least two trials of antidepressant treatment in the past.
(Therapeutic dose for at least 6 weeks)

9. Patients currently taking or have taken the following medications within the past 6
months.

- Centrally acting dopamine antagonists

- MAOI

10. Patients considered unlikely to co-operate in the study, and/or poor compliance
anticipated by the investigator.

11. Patients who have clinical significant hypotension or any clinical significant ECG
abnormality at screening.

12. Any other clinically relevant acute or chronic diseases which could interfere with
patients' safety during the trial, or expose them to undue risk, or which could
interfere with study objectives.

13. Patients who have participated in another clinical trial with an investigational drug
within previous 30 days or 5 half-lives whichever is longer.