The Efficacy And Safety Of Mitizodone Phosphate Tablets In The Treatment of Patient With Major Depressive Disorder

Study Overview
=================
Brief Summary
-----------------
This is a phase 2 and 3 adaptive design study for Mitizodone Phosphate,to find out an optimal dose in phase 2 period and confirm the result an efficacy and safety in phase 3 period.Dose-finding will be done after 8 weeks of double-blinded treatment in phase 2 period and will be assessed by both efficacy and safety from 3 dose groups of Mitizodone Phosphate.The dose be found in phase 2 period will be evaluated on efficacy and safety when compared with placebo in phase 3 period with a duration of 8 weeks treatment.The target subjects are patients with MDD.

Official Title
-----------------
A Phase II/III ,Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Adaptive Design Study Evaluating the Efficacy And Safety of Mitizodone Phosphate Tablets in the Treatment of Patient With Major Depressive Disorder

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

Intervention / Treatment
-----------------
* Drug: Mitizodone Phosphate tablets
* Drug: Placebo-matching tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1.a Man or a woman with major depressive disorder(MDD) as the primary diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (classification code 296.22、296.23、296.32、296.33) 2.Has a Montgomery Åsberg Depression Rating Scale (MADRS) total score of 26 or greater at Screening and Baseline Visits. 3.Has a Clinical Global Impression - Severity of Illness (CGI-S) score of 4 or greater at Screening and Baseline Visits. Exclusion Criteria: 1.has major depressive disorder with psychotic features according to the DSM-5. 2.Current or history of: bipolar disorder、schizophrenia、anixety disorder、insomnia、any substance abuse or dependence and other psychiatry disorder as defined in the DSM-5. 3.Current or history of a clinically significant neurological disorder (including epilepsy、Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease). 4. has Serious body disease such as neurological disorders、cardiacvascular disorders、hepatic disorders、 renal disorders, blood system disorders and endocrine disorders. 5. Current or history of cancer( except basal cell of the skin and preinvasive carcinoma of cervix uteri). 6. Current or history of angle-closure glaucoma. 7. has made a suicide behavior in the previous 1 year ，or has a score greater than or equal to 4 on item 10 (suicidal thoughts) of MADRS . 8.has taken fluoxetine within 4 weeks prior to initial dosing. 9. has taken other antidepressive medications or antipsychotic medications within 2 weeks prior to initial dosing. 10.has psychotherap at Screening and/or Baseline Visits. 11.has had physiotherapy within 3 months prior to initial dosing. 12.Has an alanine aminotransferase, aspartate aminotransferase or total bilirubin level greater than 1.5 times the upper limits of normal. 13.Has an alanine aminotransferase, aspartate aminotransferase level greater than 2 times the upper limits of normal；or total bilirubin， direct bilirubin，creatinine level greater than 1.5 times the upper limits of normal；or a thyroid stimulating hormone value outside the normal range. 14.Has an abnormal electrocardiogram confirmed as clinically significant by the investigator. 15.Has a history of severe allergies.

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: Mitizodone Phosphate tablet 10mg<br>Mitizodone Phosphate tablet 10mg ,orally,once daily for 8 weeks, then placebo,orally,once daily for 2 weeks. | Drug: Mitizodone Phosphate tablets<br>* Mitizodone Phosphate tablets will be administered with food.<br>* Other names: HEC113995PA•H2O;|
| Experimental: Mitizodone Phosphate tablet 20mg<br>Mitizodone Phosphate tablet 10mg ,orally,once daily for 1 weeks, then Mitizodone Phosphate tablet 20mg ,orally,once daily for 7 weeks, then Mitizodone Phosphate tablet 10mg ,orally,once daily for 1 weeks, then placebo,orally,once daily for 1 weeks. | Drug: Mitizodone Phosphate tablets<br>* Mitizodone Phosphate tablets will be administered with food.<br>* Other names: HEC113995PA•H2O;|
| Experimental: Mitizodone Phosphate tablet 40mg<br>Mitizodone Phosphate tablet 10mg ,orally,once daily for 1 weeks, then Mitizodone Phosphate tablet 20mg ,orally,once daily for 1 weeks, then Mitizodone Phosphate tablet 40mg ,orally,once daily for 6 weeks, then Mitizodone Phosphate tablet 20mg ,orally,once daily for 1 weeks, then Mitizodone Phosphate tablet 10mg ,orally,once daily for 1 weeks. | Drug: Mitizodone Phosphate tablets<br>* Mitizodone Phosphate tablets will be administered with food.<br>* Other names: HEC113995PA•H2O;|
| Active Comparator: Placebo<br>Placebo,tablet,orally,once daily for 10 weeks. | Drug: Placebo-matching tablets<br>* Placebo will be administered with food.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at week 8 | The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. | baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects With a MADRS Response at Week 8 | Response is defined as a subject with a ≥50% decrease in Montgomery Åsberg Depression Rating Scale (MADRS) total score from Baseline. | baseline and week 8 | 
| Percentage of Participants in MADRS Remission at Week 8 | Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. | week 8 | 
| Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at week 1、week 2 、week 4、week 6. | The MADRS is a depression rating scale consisting of 10 items, each rated 0 (normal) to 6 (most abnormal). The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. | baseline 、 week 1、week 2 、week 4 and week 6. | 
| Change From Baseline in the Clinical Global Impression - Severity of illness (CGI-S) Total Score at week 1、week 2 、week 4、week 6、week 8. | The Clinical Global Impression-Severity of illness scale assesses the subject's Severity as assessed by the clinician at the moment on a 8-point scale: 0, not assessed ; 1, normal，not at all ill ; 2, borderline mentally ill ; 3, mildly ill ; 4, moderately ill ; 5 , markedly ill ; 6, severely ill；7，among the most extremely ill patients. | baseline、week 1、week 2 、week 4、week 6 and week 8. | 
| Clinical Global Impression - Improvement (CGI-I) Score at week 1、week 2 、week 4、week 6、Week 8 | The Clinical Global Impression- Improvement scale assesses the subject's improvement (or worsening) as assessed by the clinician relative to Baseline on a 8-point scale: 0, not assessed ;1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. | week 1、week 2 、week 4、week 6 and week 8. | 
| Change From Baseline in the hamilton anxiety rating scale （HAM-A）Total Score at week 1、week 2 、week 4、week 6、week 8. | the HAM-A is a anxiety rating scale consisting of 14 items, each rated 0 (none) to 4 (very severe). The 14 items represent the core symptoms of anxiety illness. The overall score ranges from 0 (symptoms absent) to 56 (severe anxiety). A decrease in the total score or on individual items indicates improvement. | baseline、week 1、week 2 、week 4、week 6 and week 8. |