Study to Explore the Effective Doses and to Assess the Safety and Efficacy of Hypidone Hydrochloride Tablets

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the safety and efficacy of Hypidone Hydrochloride tablets in treatment of patients with major depressive disorder (MDD) by evaluating the change of MADRS total scores from baseline to week 6.

Detailed Description
-----------------
A total of 240 major depressive disorder (MDD) subjects between the ages of 18-65 who have current major depressive disorder diagnosed by DSM-5 will be recruited, Eligible patients will be randomized with a 1:1:1:1 ratio into the 4 treatment arms to receive either Hypidone Hydrochloride tablets or placebo, and will be accepted into the protocol after review and providing voluntary written informed consent forms and completion of a comprehensive medical and psychiatric history, physical examination, mental status examination, and routine laboratory assessment. The subjects will accept the drug treatment twice daily orally for 6 weeks. During the treatment follow up will occur at 8±1 days after treatment, 15±1 days after treatment, 29±2 days after treatment , 43±2 days after treatment to evaluate the safety and efficacy of the drug.

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Placebo Controlled Study to Explore the Effective Doses and to Assess the Safety and Efficacy of Hypidone Hydrochloride Tablets in Patients With Major Depressive Disorder

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

Intervention / Treatment
-----------------
* Drug: Hypidone Hydrochloride tablets
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatient or Inpatient, 18-65 years old, male or female Current major depressive disorder diagnosed by DSM-5, single episode(296.21, 296.22, 296.23), or recurrent episode(296.31, 296.32, 296.33) Montgomery-Åsberg Depression Rating Scale (MADRS) total scores in both Screening and Baseline ≥ 26 The first item of MADRS in both Screening and Baseline ≥ 3 CGI-S in both Screening and Baseline ≥ 4 Able to provide written informed consent forms Exclusion Criteria: Subjects accord with other mental disorders diagnosed by DSM-5 Subjects who attempted to suicide, or who presently have a high risk of suicide, or with the tenth item (Suicidal ideation) of C-SSRS ≥ 3 Baseline total scores compared with the screening period, the reduction rate of MADRS ≥ 25% Subjects with serious or uncontrolled cardiovascular disease, liver disease, kidney disease, blood disease, endocrine disease, respiratory disease Subjects with clinically significant ECG abnormal (Male QTcF ≥ 450 msec, Female QTcF ≥ 470 msec) Treatment with a MAOI within the 2 weeks prior to the first dose of trial medication Practicing 2 different treatment methods of antidepressants as recommended dose of full course (≥6 weeks) Subjects who have had a Vagus Nerve Stimulation (VNS) device implanted, or who have received Modified Electric Convulsive Therapy (MECT) or Transcranial Magnetic Stimulation (TMS) within 3 months of Screening, or who received light treatment, laser treatment, acupuncture and other Chinese medicine treatment, biofeedback treatment within 2 weeks of Screening Subjects with a history of true allergic response to more than 1 class of medications Subjects who participated in a clinical trial within the last 30 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg of Hypidone Hydrochloride tablets<br>Hypidone Hydrochloride tablets 10mg/day Study,5mg tablet is to be given orally, twice daily, for 6 weeks | Drug: Hypidone Hydrochloride tablets<br>* Hypidone Hydrochloride tablets will be given orally, twice daily, for 6 weeks<br>|
| Experimental: 20 mg of Hypidone Hydrochloride tablets<br>Hypidone Hydrochloride tablets 20mg/day Study,10mg tablet is to be given orally, twice daily, for 6 weeks | Drug: Hypidone Hydrochloride tablets<br>* Hypidone Hydrochloride tablets will be given orally, twice daily, for 6 weeks<br>|
| Experimental: 40 mg of Hypidone Hydrochloride tablets<br>Hypidone Hydrochloride tablets 40mg/day Study,20mg tablet is to be given orally, twice daily, for 6 weeks | Drug: Hypidone Hydrochloride tablets<br>* Hypidone Hydrochloride tablets will be given orally, twice daily, for 6 weeks<br>|
| Placebo Comparator: comparator<br>Placebo tablets is to be given orally, twice daily, for 6 weeks | Other: Placebo<br>* Placebo tablets will be given orally, twice daily, for 6 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) | Change from baseline in MADRS scores，the *total* score ranges[0,60],higher values represent a worse outcome | Baseline,43 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Scale 17 items(HAMD17) | Change from baseline in HAMD17 scores,the *total* score ranges[0,50],higher values represent a worse outcome | Baseline,43 days after treatment | 
| Hamilton Anxiety Rating Scale (HAM-A) | Change from baseline in HAM-A scores,the *total* score ranges[0,56],higher values represent a worse outcome | Baseline,43 days after treatment | 
| Clinical Global Impression of Severity Scale(CGI-S) | Change from baseline in CGI-S scores,the *total* score ranges[0,7],higher values represent a worse outcome | Screening,Baseline, 8 day after treatment,15 day after treatment,29 day after treatment,43 day after treatment | 
| Clinical Global Impression of Improvement Scale(CGI-I) | the *total* score ranges[0,7],higher values represent a worse outcome | 8 day after treatment,15 day after treatment,29 day after treatment,43 day after treatment | 
| Change in Digit Symbol Substitution Test (DSST) |  | Baseline, 43 days after treatment | 
| Change in Trail Making Test Parts A&B (TMT) |  | Baseline, 43 days after treatment |