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

Phase 2

Completed

Conditions: Major Depressive Disorder

Interventions: Drug: PDC-1421 Capsule
Drug: placebo

Registration Number: NCT02395978

Lead Sponsor: BioLite, Inc.

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part II: 2 PDC-1421 Capsule	PDC-1421 Capsule	2 PDC-1421 Capsule TID, p.o. after meal for 42 days
Part I: 1 PDC-1421 Capsule	PDC-1421 Capsule	1 PDC-1421 Capsule TID, p.o. after meal for 28 days
Part I: 2 PDC-1421 Capsule	PDC-1421 Capsule	2 PDC-1421 Capsule TID, p.o. after meal for 28 days
Part II: 1 PDC-1421 Capsule plus 1 placebo	PDC-1421 Capsule	1 PDC-1421 Capsule plus 1 placebo TID, p.o. after meal for 42 days
Part II: 1 PDC-1421 Capsule plus 1 placebo	placebo	1 PDC-1421 Capsule plus 1 placebo TID, p.o. after meal for 42 days
Part II: 2 placebo	placebo	2 placebo TID, p.o. after meal for 42 days

Primary Outcome Measures

Name	Time	Method
Change of Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 6 Compared to Placebo for Part II.	From Baseline to Week 6	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).

Secondary Outcome Measures

Name	Time	Method
Change of Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline to Week 2, 4 and 7 Part II.	From Baseline to Week 2, 4, 7	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).
Change of Hamilton Depression Rating Scale (HAM-D-17) Total Score From Baseline to Week 2, 4, 6 and 7 for Part II.	From Baseline to Week 2, 4, 6 and 7	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.
Change of Hamilton Anxiety Rating Scale (HAM-A) Total Score From Baseline to Week 2, 4, 6 and 7 for Part II.	From Baseline to Week 2, 4, 6 and 7	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.
Change of Depression and Somatic Symptoms Scale (DSSS) From Baseline to Week 2, 4, 6 and 7 for Part II	From Baseline to Week 2, 4, 6 and 7	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).
Change of Clinical Global Impression Scale - Severity (CGI-S) From Baseline to Week 2, 4, 6 and 7 for Part II.	From Baseline to Week 2, 4, 6 and 7	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).
Percentage of Responders and Partial Responders in MADRS by Week 2, 4, 6 and 7 Weeks for Part II.	From Baseline to Week 2, 4, 6 and 7	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.
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.	From screen to Week 2, 4, 6 and 7	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.
Clinical Global Impression Scale -Improvement (CGI-I) From Baseline to Week 2, 4, 6 and 7 for Part II.	From Baseline to Week 2, 4, 6 and 7	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).
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.	From screen to Week 2, 4, 6 and 7	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.

Trial Locations

Locations (5): Tri-Service General Hospital, Neihu Main Facility
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Taipei, Taiwan
Linkou Chang Gung Memorial Hospital
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Taoyuan, Taiwan
Taipei Veterans General Hospital
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Taipei, Taiwan
Stanford Depression Research Clinic
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San Francisco, California, United States
Wan Fang Hospital
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Taipei, Taiwan