A Phase II Study of PDC-1421 Capsule to Evaluate the Safety and Efficacy in Patients With Major Depressive Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy in patients with major depressive disorder.

Detailed Description
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The screening phase is intended for diagnosing and assessing the patient for possible inclusion in the study and for providing an adequate washout period. The following study will be conducted in two parts. Part I is an open-label study, multiple center and dose escalation evaluation in twelve patients. Six subjects each will be evaluated for safety and efficacy assessments at 1 or 2 capsules TID dose for 28 days, sequentially. Each of them will be assessed twice in the first week after administration of PDC-1421 Capsules and once a week in the following treatment. Part II is a randomized, double-blind, placebo-controlled, parallel-group study. 60 subjects will be randomly assigned on a 1:1:1 basis to one of the three arms (1 PDC-1421 Capsule plus 1 placebo TID, 2 PDC-1421 Capsules TID, 2 placebo TID) for 6 weeks and evaluated the safety and efficacy every two weeks during the treatment period.

Official Title
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A Phase II Study of PDC-1421 Capsule to Evaluate the Safety and Efficacy in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients aged 20-65 years Subjects must be able to understand and willing to sign informed consent Female subjects of child-bearing potential must test negative to pregnancy and use appropriate birth control method from the beginning of study to the 15 days later after ending of study Met criteria for MDD without psychotic features as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision® (DSM-IV-TR) and confirmed by use of the Mini International Neuropsychiatric Interview (MINI). 17-item HAM-D (Hamilton Rating Scale for Depression) total score ≧20 and CGI (Clinical Global Impression) total score ≧4 Exclusion Criteria: Have a current or previous major psychiatric disorders which be defined to be per the DSM-IV-TR, including obsessive-compulsive disorder, posttraumatic stress disorder, bipolar I or II, manic or hypomanic episode, schizophrenia, major Axis II disorders which might compromise the study, and major depression with psychotic symptoms, mental retardation. Use of any treatment for MDD in the last 2 weeks before visit 1 (4 weeks for fluoxetine). Use of psychoactive drugs within the last 2 weeks before visit 1 other than that subjects had insomnia who need the treatment as determined by the Investigator. Subjects who were non-responsive to two or more courses of antidepressant medications given 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, laboratory values as determined by the investigator which might interfere with the study. Any organic disorder caused u medical related depression which cannot be under well-controlled such as clinically significant in neurological, gastrointestinal, renal, hepatic, cardiovascular, respiratory, metabolic, endocrine, hematological or other major disorders Have a high suicidal risk as measured by MINI. Have a history of substance abuse within the past 6 months or a positive urine drug screen for any substance of abuse at visit 1. Have a history of severe allergies to more than 1 class of medication or multiple adverse drug reactions.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part I is a open label, dose escalation with two dosage levels study. Part II is a randomized (1:1:1), double-blind, placebo-controlled, parallel groups with three treatment arms.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: 1 PDC-1421 Capsule<br>1 PDC-1421 Capsule TID, 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>* Other names: BLI-1005;|
| Experimental: Part I: 2 PDC-1421 Capsule<br>2 PDC-1421 Capsule TID, 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>* Other names: BLI-1005;|
| Experimental: Part II: 2 PDC-1421 Capsule<br>2 PDC-1421 Capsule TID, p.o. after meal for 42 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>* Other names: BLI-1005;|
| Experimental: Part II: 1 PDC-1421 Capsule plus 1 placebo<br>1 PDC-1421 Capsule plus 1 placebo TID, p.o. after meal for 42 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>* Other names: BLI-1005;Drug: placebo<br>* Placebo contained corn starch.<br>|
| Placebo Comparator: Part II: 2 placebo<br>2 placebo TID, p.o. after meal for 42 days | Drug: placebo<br>* Placebo contained corn starch.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 6 Compared to Placebo for Part II. | The MADRS is a 10-item checklist of depressive symptoms. 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 MADRS score was calculated by summing the ratings of all items. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity). | From Baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 2, 4 and 7 Part II. | The MADRS is a 10-item checklist of depressive symptoms. 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 MADRS score was calculated by summing the ratings of all items. The total MADRS score for this measure ranges from 0 (absence of symptoms) to 60 (maximum severity). | From Baseline to Week 2, 4, 7 | 
| Change of Hamilton Depression Rating Scale (HAM-D-17) Total Score From Baseline to Week 2, 4, 6 and 7 for Part II. | HAM-D-17 scale is a clinician rated scale comprised of 17 items aimed at assessing depression severity among patients for treatment. Each item on the questionnaire is scored on a 3 point (8 items) or 5 point (9 items) scale, depending on the item. The total HAM-D-17 score was calculated by summing the ratings of all items. . The highest possible score was 52, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. | From Baseline to Week 2, 4, 6 and 7 | 
| Change of Hamilton Anxiety Rating Scale (HAM-A) Total Score From Baseline to Week 2, 4, 6 and 7 for Part II. | HAM-A is a series of questions related to symptoms of anxiety. It rates the individual on a five-point scale (0 4) for each of the 14 items. Seven of the items specifically address psychic anxiety and the remaining seven items address somatic anxiety. The total HAM-A score was calculated by summing the ratings of all items. The total HAM-A score ranges from 0 to 56. The higher score represented a more severe measure of anxiety. | From Baseline to Week 2, 4, 6 and 7 | 
| Change of Depression and Somatic Symptoms Scale (DSSS) From Baseline to Week 2, 4, 6 and 7 for Part II | DSSS includes a simultaneous measure of depression and somatic symptoms that two issues frequently co-occur. Consisting of 22 items, the DSSS includes 12 depression-related items (even items + item-21) and 10 somatic items (add items without item-21) - 5 of which query pain symptoms(item-1, 7, 11, 13, 17), forming a pain sub-scale. Each Item is rated on a scale of 0 (Absent) - 3 (Severe). DSSS Depression Sub-Score was calculated by summing the 12 depression-related items with ranges from 0 (absence of symptoms) to 36 (maximum severity). DSSS Somatic Sub-Score was calculated by summing the 10 somatin-related items with ranges from 0 (absence of symptoms) to 30 (maximum severity). DSSS Pain Sub-Score was calculated by summing the 5 pain-related items with ranges from 0 (absence of symptoms) to 15 (maximum severity). | From Baseline to Week 2, 4, 6 and 7 | 
| Change of Clinical Global Impression Scale - Severity (CGI-S) From Baseline to Week 2, 4, 6 and 7 for Part II. | CGI-Severity (CGI-S) is a 7-point scale which rates illness severity of psychopathology from 1 (normal, not at all ill) to 7 (among the most extremely ill). | From Baseline to Week 2, 4, 6 and 7 | 
| Percentage of Responders and Partial Responders in MADRS by Week 2, 4, 6 and 7 Weeks for Part II. | Responder defined as a participant with ≧50% decrease from baseline in total score. Partial responder defined as a participant with a ≧25 and <50% decrease from baseline in total score. | From Baseline to Week 2, 4, 6 and 7 | 
| Number of Subjects With Suicidal Ideations Collected by Columbia-Suicide Severity Rating Scale (C-SSRS) From Baseline to Week 2, 4, 6 and 7 for Part II. | The FDA has adopted the 11 categories defined in the C-SSRS (Category 1 to 5 for suicidal ideation , Category 6 to 10 for suicidal behavior, and Category 11 for self-injurious behavior without suicidal intent) as their standard. Number of subjects with Suicidal Ideation: The maximum suicidal ideation category (1-5 on the C-SSRS) present at the assessment. Assign a score of 0 if no ideation is present. | From screen to Week 2, 4, 6 and 7 | 
| Number of Subjects With Suicidal Behaviors Collected by Columbia-Suicide Severity Rating Scale (C-SSRS) From Baseline to Week 2, 4, 6 and 7 for Part II. | The FDA has adopted the 11 categories defined in the C-SSRS (Category 1 to 5 for suicidal ideation , Category 6 to 10 for suicidal behavior, and Category 11 for self-injurious behavior without suicidal intent) as their standard. Number of subjects with Suicidal Behavior: The maximum suicidal ideation category (6-10 on the C-SSRS) present at the assessment. Assign a score of 0 if no ideation is present. | From screen to Week 2, 4, 6 and 7 | 
| Clinical Global Impression Scale -Improvement (CGI-I) From Baseline to Week 2, 4, 6 and 7 for Part II. | CGI-Improvement (CGI-I) is a 7-point scale which rates illness has improved or worsened relative to a baseline state from 1 (Very much improved) to 7 (Very much worse). | From Baseline to Week 2, 4, 6 and 7 |