Study of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression

Efficacy and Safety of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression: A Multicenter, Randomized, Double-blind, Double-dummy, Active- and Placebo-controlled, Parallel-group, Phase II Study

The purpose of this study is to evaluate the efficacy and safety of Ammoxetine hydrochloride enteric-coated tablets in subjects with depression.

In this study, a randomized, double-blind, duloxetine hydrochloride enteric coated capsule positive and placebo-controlled multicenter study was used to evaluate the efficacy and safety of different doses of amxetine hydrochloride enteric coated tablets in the treatment of depression.

Inclusion Criteria:

• 1. Subjects aged 18 and 65 years (inclusive), no gender limitation;
• 2. Subject has recurrent Major Depressive Disorder (MDD) as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5, 5th Edition), single episode or recurrent episodes (DSM-IV-TR criteria, classification code 296.2/296.3), without psychotic symptoms;
• 3. Subjects with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 26 and subjects with Clinical Global Impression Scale Disease Severity CGI-S severity score ≥ 4 at screening and baseline;
• 4. For male or female with fertility: must agree to use effective contraceptive method during the study and within 1 month after the end of the trial;
• 5. Be able to read and understand the content of the informed consent and voluntarily sign the informed consent.

Exclusion Criteria:

• 1. Subjects with ≥ 25% reduction in MADRS score in the baseline period compared to the screening period;
• 2. Subjects meet DSM-5 diagnostic criteria for other mental disorders (schizophrenia spectrum and other psychiatric disorders, bipolar and related disorders, anxiety disorders, obsessive-compulsive and related disorders, somatic symptoms and related disorders, etc.);
• 3. Subjects are diagnosed as DSM-5 drug use disorder;
• 4. Refractory depression (subjects who had previously used two different mechanisms of antidepressants and failed after receiving adequate treatment (at least 8 weeks);
• 5. Organic mental disorders, such as depression caused by hypothyroidism;
• 6. Depression caused by psychoactive substances or non-addictive substances;
• 7. Subjects with other diseases or other types of mental disorders with depressive symptoms;
• 8. Subjects assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) and those judged by the investigator to be at risk for suicide, or to have engaged in suicidal behaviour within 6 months prior to screening;
• 9. Allergic constitution (e.g. allergic to two or more drugs or to serotonin norepinephrine reuptake inhibitors (SNRIs));
• 10.Previous history of malignant tumor;
• 11.Previous history of elevated intraocular pressure or narrow angle glaucoma;
• 12.Subjects suffered from other serious physical diseases, such as uncontrolled hypertension or unstable cardiovascular disease, serious liver disease, kidney disease, blood disease, endocrine disease, neurological disease, etc;
• 13.Subjects with diseases that interfere with the absorption of oral medications, such as active bowel disease, partial or complete intestinal obstruction, chronic diarrhea, etc;
• 14.Subjects who have used drugs or foods that alter the activity of liver enzymes (CYP2C19 and CYP3A4) such as dexamethasone, rifampicin, omeprazole, grapefruit, etc., within 4 weeks prior to screening;
• 15.12-lead ECG system showed degree II or III atrioventricular block, long QT syndrome or QTc > 450 ms (male) / 470 ms (female) at screening;
• 16.Subjects discontinued use of a combination of drugs that prolong the QT interval prior to randomization, or drugs that can cause prolongation of the QT and may induce TdP for less than 5 half-lives of the drugs;
• 17.In screening period, subjects with ALT or AST 1.5 times higher than the upper limit of laboratory normal value; creatinine 1.1 times higher than the upper limit of normal value; and abnormalities in 2 or more of the 5 indicators of thyroid function (TSH, FT3, FT4, TT3 or TT4 0.9 times below the lower limit of normal value or 1.1 times above the upper limit of normal value);
• 18.Subjects have used monoamine oxidase inhibitors within 2 weeks before randomization;
• 19.Subjects discontinuing antipsychotics, antidepressants or mood stabilizers for less than 5 half-lives of the drug before randomization;
• 20.Subjects who are using long half-life drugs (such as fluoxetine, long-acting antipsychotics, etc.);
• 21.Subjects who have received electroconvulsive therapy (ECT), systematic psychotherapy (interpersonal relationship therapy, dynamic therapy, cognitive behavior therapy, etc.), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), phototherapy, etc. within 3 months before screening, or subjects who, in the judgment of the investigator, are currently in need of such treatment;
• 22.Female subjects who are breastfeeding or have a positive pregnancy test during the screening period or during the study;
• 23.Alcohol or drug dependence within 3 months before screening;
• 24.Subjects who have participated in other clinical trials within 3 months before screening and are taking the test drug;
• 25.Subjects who, in the opinion of the investigator, have any other condition that makes them unsuitable for participation in this trial.