A Study in Patients With Major Depressive Disorder
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).
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.