A Phase I/II Study of PDC-1421 for Treating Depression in Cancer Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and the effective doses of PDC-1421 in cancer patients with depression.

Official Title
-----------------
A Phase I/II Study of PDC-1421 for Treating Depression in Cancer Patients: Part I Dose Escalation

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: PDC-1421 Capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Eligibility Criteria 21 to 85 Years of age Diagnosis of Stage I, II or III cancer Histologically-proven malignancy Receiving or within one year of having received cancer treatment with radiation and/or chemotherapy Montgomery and Åsberg Depression Rating Scale (MADRS) ≥ 20 (moderate to severe depressive symptoms) Duration of depressive symptoms ≥ 2 weeks by patient report. No active/acute suicidality requiring immediate care or psychiatric hospitalization Sufficient English language proficiency to complete all assessments without assistance Able to swallow pills No severe anemia, defined as hemoglobin < 10 g/dL No history of multiple adverse drug reactions or allergy to study drugs Not pregnant No history of head trauma No history of epilepsy No other concurrent antidepressant medications Exclusion Criteria Have a current or previous diagnosis of or history consistent with obsessive-compulsive disorder, posttraumatic stress disorder, bipolar I or II, manic or hypomanic episodes, schizophrenia, major Axis II disorders which might compromise the study, or major depression with psychotic symptoms, as assessed using the MINI International Neuropsychiatric Interview (MINI Plus). Have a documented history of an intellectual disability. Use of any antidepressant medication in the last 2 weeks before visit 1 (4 weeks for fluoxetine). Currently being treated with tamoxifen. Subjects who were non-responsive to two or more courses of antidepressant medications given at an adequate dosage* for symptom treatment within four weeks, or by the judgment of the investigator considered to have treatment resistant depression (TRD), or a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or psychosurgery within the last year. Have a history of any seizure disorder. Any clinically significant abnormal vital sign, ECG, or laboratory values as determined by the investigator which might interfere with the study. Have a high suicidal risk as assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS). High suicidal risk is indicated by: A positive response to question 4 or 5, indicating endorsement of suicidal ideation with at least some intent to act in the past month; and/or A positive response to part two of question 6, indicating the presence of any suicidal behavior in the past 3 months. Have a history of substance dependence/abuse** within the past 6 months or a positive drug screen result during the screening period. Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions. * An adequate dosage of the antidepressant medication is defined as the average of the usual dose (mg/day) recommended in American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition. E.g. the usual dose of Citalopram is 20-60 mg/day, the adequate dosage is 40 mg/day. ** Tobacco is excluded here, and alcohol abuse is defined as average pure alcohol intake is more than 112 g (for male) or 56 g (for female) per week and/or with Alcohol withdrawal syndrome. Pure alcohol intake =% (Concentration or alcohol content) x c.c. (volume)x 0.79 (density of alcohol). Result of serum ethanol test should be equal to or lower than 10.0 mg/dL to be determined as eligible for the trial. If test result is between 10.1 to 29.9 mg/dL, only one re-test is allowed per subject to meet the criterion. Subject with test result equal to or higher than 30.0 mg/dL is to be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 PDC-1421 Capsule<br>1 PDC-1421 Capsule, trice daily, p.o. after meal for 28 days | Drug: PDC-1421 Capsule<br>* PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as active ingredient.<br>|
| Experimental: 2 PDC-1421 Capsules<br>2 PDC-1421 Capsule, trice daily, p.o. after meal for 28 days | Drug: PDC-1421 Capsule<br>* PDC-1421 Capsule is a botanical investigational new drug containing the extract of Radix Polygalae (Polygala tenuifolia Willd.) as active ingredient.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg Depression Rating Scale (MADRS) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 1, 2, 3, 4, and 5 in patients taking 1 or 2 PDC-1421 capsules. The MADRS is a 10-item checklist including 1) depression [apparent]; 2) depression [reported]; 3) loss of interest; 4) suicidal ideation; 5) tension; 6) reduced appetite; 7) insomnia; 8) difficulty in activities; 9) concentration; and 10) pessimism. The MADRS is administered by a trained interviewer. Each item is rated on a scale of 0-6, with anchors at 2-point intervals; higher scores indicating more severity (i.e., ranging from 0 [no sadness] to 6 [extremely despondent]). The total score is used to define treatment response (≥50% reduction from baseline) and partial response (20-49% reduction from baseline). Remission is defined as a score of < 10. The following are used as an interpretation of scores: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression | 5 weeks |