Clinical trial NCT05762458: The Study of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression
Official title: Efficacy and Safety of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Phase Ⅱ Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Major Depressive Disorder (MDD)
Keywords: MDD
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-09
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: In this study, a randomized, double-blind, placebo-controlled multicenter study will be conducted to evaluate the efficacy and safety of different doses of Ammoxetine hydrochloride enteric coated tablets in the treatment of depression.

Eligibility criteria: 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 at screening and baseline;
4. Subjects with Clinical Global Impression Scale Disease Severity CGI-S severity score ≥ 4 at screening and baseline;
5. A score of ≥2 on the first item (depressed mood) of the HAMD-17 scale at the screening and baseline;
6. 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;
7. 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 behavior 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, etc., within 4 weeks prior to randomization;
15. 12-lead ECG system showed degree Ⅱ or Ш atrioventricular block, long QT syndrome or QTc \> 450 ms (male) / 460 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 2 times higher than the upper limit of laboratory 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.

Primary outcomes:
measure: Change from baseline in Montgomery Asperger Depression Scale (MADRS) score at the end of treatment (week 8)
timeFrame: Baseline and week 8
Secondary outcomes:
measure: Change from baseline in Hamilton Depression Scale (HAMD-17) at week 1, 2, 4, 6, 8
timeFrame: Baseline, week 1, 2, 4 ,6 and 8
measure: Change from baseline in Hamilton Anxiety Inventory (HAMA) scores at week 1, 2, 4, 6, 8
timeFrame: Baseline, week 1, 2, 4 ,6 and 8
measure: Change from baseline in CGI-S score at week 1, 2, 4, 6, 8
timeFrame: Baseline, week 1, 2, 4, 6 and 8
measure: Change from baseline in MADRS score at week 1, 2, 4, 6
timeFrame: baseline, week 1, 2 and 4, 6
measure: CGI-I scores at the end of 8 weeks of treatment at week 1, 2, 4, 6, 8
timeFrame: Baseline, week 1, 2, 4, 6 and 8
measure: The efficiency and remission of the MADRS score
timeFrame: Baseline, Baseline, week 1, 2, 4, 6 and 8
measure: Efficacy and remission of HAMD-17 scores
timeFrame: Baseline, week 1, 2, 4, 6 and 8
measure: The percentage of subjects with a MARDS score reduction ≥ 25%
timeFrame: Week 1 and 2
measure: Incidence of adverse events (AE)
timeFrame: Throughout the study period（From baseline to week 10）
Other outcomes:
Locations:
Study officials:
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