Clinical trial NCT05018013: 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, Double-dummy, Active- and Placebo-controlled, Parallel-group, Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Major Depressive Disorder (MDD)
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-24
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, 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.

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 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.

Primary outcomes:
measure: Change from baseline in Montgomery Asperger Depression Scale (MADRS) score at the end of treatment (week 6)
timeFrame: Baseline and week 6
Secondary outcomes:
measure: Change from baseline in Hamilton Depression Scale (HAMD-17) at week 1, 2, 4, 6
timeFrame: Baseline, week 1, 2, 4 and 6
measure: Change from baseline in Hamilton Anxiety Inventory (HAMA) scores at week 1, 2, 4, 6
timeFrame: Baseline, week 1, 2, 4 and 6
measure: Change from baseline in CGI-S score at week 1, 2, 4, 6,7
timeFrame: Baseline, week 1, 2, 4, 6 and 7
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,an average of 18 months
measure: Change from baseline in MADRS score at week 1, 2, 4
timeFrame: baseline, week 1, 2 and 4
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
affiliation: CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd
name: Huang Yanli, MD
role: STUDY_DIRECTOR
affiliation: Shanghai Mental Health Center
name: Li Huafang, Ph.D
role: STUDY_CHAIR
References: