Compare the Efficacy and Safety of KH607 Tablets Versus Vortioxetine Hydrobromide Tablets in Adult Patients With Major Depressive Disorder

1. Other psychiatric disorders meeting DSM-5 criteria, including but not limited to schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, panic disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, anorexia nervosa and bulimia nervosa, neurodevelopmental disorders, schizoaffective disorder, or any other psychiatric disorder that, in the Investigator's judgment, may compromise subject compliance.

2. A reduction of ≥25% in MADRS total score at baseline compared with the screening visit (this criterion does not apply if baseline and screening assessments are performed at the same visit).

3. Participants with clinically significant risk of suicide or self-harm, defined as any of the following:

1. A score ≥4 on Item 10 (Suicidal Thoughts) of the MADRS;

2. An answer of "Yes" to Question 4 (active suicidal ideation with intent without specific plan) or Question 5 (active suicidal ideation with specific plan and intent) of the C-SSRS within the past 6 months at screening, or a suicide-related behavior within the past 6 months (any "Yes" response for Actual Attempt, Interrupted Attempt, or Aborted Attempt).

4. Participants meeting any of the following depressive disorder diagnoses:

1. Poor response to adequate dose and adequate duration (at least 6 weeks) of two or more antidepressants with distinct pharmacological mechanisms during a prior depressive episode (based on Investigator interview, to be adjudicated and documented by the Investigator);

2. Depressive disorder secondary to other psychiatric disorders or somatic diseases (e.g., depression induced by hypothyroidism);

3. Substance/medication-induced depressive disorder.

5. Participants receiving structured psychotherapy (interpersonal therapy, psychodynamic therapy, cognitive behavioral therapy, etc.), music therapy, exercise therapy, acupuncture, or other therapies from screening through baseline, who require continuation of such therapies during the study.

6. Receipt of depression-related neuromodulation therapies within 1 month prior to enrollment, including but not limited to modified electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS).

7. Prior use of atypical antipsychotics or mood stabilizers during the current depressive episode (e.g., olanzapine, risperidone, quetiapine, aripiprazole, brexpiprazole, ziprasidone, cariprazine, valproate, lithium carbonate).

8. Use of any strong CYP3A4 inhibitor or inducer within 14 days (or 5 half-lives, whichever is longer) prior to enrollment.

9. Abnormal hepatic or renal function prior to enrollment: liver function abnormalities (ALT or AST \>2×ULN), renal function abnormalities (Cr \>1.5×ULN), or other conditions deemed inappropriate for enrollment by the Investigator.

10. Positive test results at screening for active hepatitis B (HBV-DNA ≥1000 copies/mL or 200 IU/mL), hepatitis C antibody, syphilis antibody, or human immunodeficiency virus (HIV) antibody.

11. 12-lead electrocardiogram (ECG) showing second-degree or third-degree atrioventricular block, long QT syndrome, or QTcF \>450 ms (male) / 460 ms (female) prior to enrollment; or other conditions unsuitable for participation as judged by the Investigator (e.g., clinically significant tachyarrhythmia requiring intervention).

12. Severe hypothyroidism (TSH ≥10.0 mIU/L).

13. Participants with current obstructive sleep apnea and/or narcolepsy.

14. Participants who have known or suspected hypersensitivity to vortioxetine hydrobromide, the investigational product or their excipients, or those with allergic diathesis (defined as allergy to at least two different substances).

15. Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test at screening.

16. Participants or their partners planning pregnancy, sperm donation, or oocyte donation during the study and within 6 months after the last study drug administration, and unwilling to use adequate and effective contraception throughout this period.

17. Participants who cannot avoid driving, operating hazardous machinery, or working at heights from the first dose of study drug until 2 weeks after the last dose.

18. History of seizures, or any other medical conditions associated with an increased seizure risk (e.g., stroke, severe head trauma, significant metabolic disturbances).

19. History of narrow-angle glaucoma or other conditions resulting in elevated intraocular pressure.

20. Any other conditions that, in the Investigator's opinion, render the subject unsuitable for participation in this study.

What this study is about