Comparison of Anyu Peibo With Placebo in Treatment of MDD in China

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of Anyu Peibo Capsule comparing with placebo in the treatment of Chinese Patients with Depression.

Official Title
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Efficacy and Safety Study of Anyu Peibo in the Treatment of Major Depressive Disorder(MDD): a Ⅲ Randomized, Double-Blind, Placebo-Paralleled, Multicenter Clinical Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Anyu Peibo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult with primary diagnosis of major depressive disorder(MDD) based on the criteria of DSM-5, single episode or recurrent episode. [296.21; 296.22; 296.23; 296.31; 296.32; 296.33] The total score of MADRS is ≥26 in both screening visit and baseline visit. The first item of MADRS is ≥3 in both screening visit and baseline visit. CGI-S is ≥4 in both screening visit and baseline visit. The subject understands and consents to takes part in this clinical trials. The subjects should sign informed consent form. Exclusion Criteria: The subject has a current psychiatric diagnosis other than depression. The subject has a suicide attempt within recent 1 year, or has a currently significant risk of suicide, or has a score ≥3 on item 10 (suicidal ideation) of MADRS. The subject has a current depressive episode due to somatic general disease or a neurological disease, such as hypothyroidism. When the MADRS total score of baseline visit compares with the screening visit, the decreasing rate is ≥25%. Known hypersensitivity to Big Leaf Ju, or at least to two kinds of drugs. Any unstable cardiovascular, hepatic, renal, blood, endocrine, or other medical disease. Any neurological disease (such as Parkinson's Disease, cerebrovascular accident and epilepsy) or cerebral injury (traumatic or disease related). Had a history or a high risk related disease or medication of seizure disorder, except infantile febrile convulsion. The subject could not take medication or has a disease affecting drug absorption, distribution, metabolism and excretion. Clinically significant electrocardiographic(ECG) abnormalities in screening visit. Such as QTc ≥450 ms in male or ≥470 ms in female. Clinically significant abnormal laboratory values (eg. ALT or AST value above 2 times of clinical top-limit; Cr value above normal top-limit; thyroid gland function index (≥ 2 items in 5 items) above 1.2 times or below 0.8 times of the normal range, or investigator diagnosed with hypothyroidism or hyperthyroidism). The subject who used at least two different antidepressants with recommended dose and adequate duration (maximum dosage by at least 4 weeks according to label) treatment still had no respond. The subject uses antidepressant drug normally before 2 weeks of screening, and stops using psychotropic drug before randomization less than 5 half-life period (monoamine oxidase inhibitor: at least 2 weeks; fluoxetine: at least 1 month). The subject received systematic light therapy, laser therapy and acupuncture or other Traditional Chinese Medicine, or systemic biofeedback therap within 2 weeks. The subject received modified ECT, trans-cranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) or systematic psychotherapy within 3 months. Women who were pregnant, breast-feeding, or serum-HCG(+) on screening; or planning to become pregnant within 3 months after kick-off of clinical trial. Education level below junior high school. The subject has participated in a drug clinical trial within 1 month before screening. The investigator thinks the subject is unsuitable to enroll in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anyu Peibo<br>Anyu Peibo Capsule, oral, 0.8g twice per day | Drug: Anyu Peibo<br>* Anyu Peibo Capsule, 0.8g twice per day, oral after breakfast and supper<br>|
| Placebo Comparator: Placebo<br>Placebo,oral, twice per day | Drug: Placebo<br>* Placebo Capsule, twice per day, oral after breakfast and supper<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of total score from baseline in Montgomery Asberg Depression Rating Scale （MADRS） | the minimum and maximum values of MADRS are from 0 to 60, and higher scores mean a worse outcome | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission Rate according to total score of MADRS at the end of study | Remission=at the end of study, total score of MADRS ≤10, the minimum and maximum values of MADRS are from 0 to 60, and higher scores mean a worse outcome | 8 weeks | 
| Clinical Remission Rate according to 17-items Hamilton Depression Scale (HAMD17) total score at the end of study | Remission=at the end of study, total score of HAMD17 ≤7, the minimum and maximum values of HAMD17 are from 0 to 52, and higher scores mean a worse outcome | 8 weeks | 
| The change of total score of MADRS by time | the minimum and maximum values of MADRS are from 0 to 60, and higher scores mean a worse outcome | 8 weeks | 
| The change of total score from baseline in HAMD17 | the minimum and maximum values of HAMD17 are from 0 to 52, and higher scores mean a worse outcome | 8 weeks | 
| The change of total score from baseline in Hamilton Anxiety Scale (HAMA) | the minimum and maximum values of HAMA are from 0 to 56, and higher scores mean a worse outcome | 8 weeks | 
| The change of score from baseline in Clinical Global Impression-Severity of Illness (CGI-S) | the minimum and maximum values of CGI-S are from 1 to 7, and higher scores mean a worse outcome | 8 weeks | 
| Clinical Global Impression-Severity of Illness (CGI-I) score | the minimum and maximum values of CGI-I are from 1 to 7, and higher scores mean a worse outcome | 8 weeks | 
| The change of total score from baseline in Discriminative Scale Space Tracker (DSST) | the minimum and maximum values of DSST are from 0 to 90, and higher scores mean a better outcome | 8 weeks | 
| The change of total score from baseline in Trail Making Test (TMT) A&B | the minimum and maximum values of TMT are from 0 to 300, and higher scores mean a worse outcome | 8 weeks | 
| The change of total score from baseline in Sheehan Disability Scale (SDS) | the minimum and maximum values of SDS are from 0 to 10, and higher scores mean a worse outcome | 8 weeks | 
| Proportion of subjects who withdrew from clinical trial due to poor efficacy | Investigator will assess subject's efficacy according to his/her clinical status with rating scales, including MADRS, HAMD17, HAMA and CGI, which already listed in Outcome | 8 weeks | 
| Proportion of subjects who combined medication to treat insomnia |  | 8 weeks | 
| Incidence rate of AE | AE=Adverse Events | 8 weeks | 
| Breath Rate | per minutes | 8 weeks | 
| Pulse Rate | per minutes | 8 weeks | 
| Heartbeat Rate | per minutes | 8 weeks | 
| Diastolic blood pressure | Sitting position, mmHg | 8 weeks | 
| Systolic blood pressure | Sitting position, mmHg | 8 weeks | 
| Electrocardiogram(ECG) | the number of subjects with abnormal ECG report by 12-lead electrocardiogram | 8 weeks | 
| Assessment of Arizona Sexual Experience Scale (ASES) | the minimum and maximum values of ASES are from 1 to 6, and higher scores mean a worse outcome | 8 weeks | 
| Number of Participants with AE result in early withdrawal from clinical trials |  | 8 weeks | 
| Number of Participants with Serious Adverse Event (SAE) result in early withdrawal from clinical trials |  | 8 weeks | 
| Number of Emerging AE during drug withdrawal period |  | 9 weeks |