A Study of Vortioxetine in Japanese Pediatric Patients With Major Depressive Disorder

A Randomized, Double-blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Once-Daily Oral Administration of Vortioxetine in Japanese Pediatric Patients 12 to 17 Years of Age With Major Depressive Disorder (MDD)

The main aim of the study is to check how well vortioxetine 10 mg/day or 20 mg/day works and to check for side effects compared to a placebo on depression symptoms in Japanese teenagers aged 12 to 17 years with a diagnosis of Major Depressive Disorder (MDD).

The overall time each participant will be in the study is about 20 weeks. This includes up to 15 days (about 2 weeks) to check who can take part, a 14-week period where everyone receives vortioxetine or a placebo, and after that, a 4-week period to check for any side effects after treatment.

During the study, participants will visit their clinic 13 times.

Inclusion Criteria:

1. The Japanese participant is a male or female, aged 12 to 17 years at the time of informed consent (patients who turn 18 years during the trial will be allowed to continue in the trial).

2. The participant is capable of communicating with the site personnel.

3. The participant is able to understand the informed assent form or the ICF and parent(s)/legal guardian(s) are able to read and understand the ICF. The participant is able and willing to accept video recording at the assessment by the trial site and evaluation by third party evaluators (Central Evaluating Committee).

4. The participant has provided the written informed assent as much as possible to participation and parent(s)/legal guardian(s) signed the ICF.

5. The participant and parent(s)/legal guardian(s) are willing and able to attend trial appointments within the specified time windows.

6. The participant is an outpatient consulting a clinician.

7. The participant has a primary diagnosis of MDD or persistent depressive disorder and fully meet the criteria for major depressive episodes according to DSM-5-TR without psychotic features although co-morbid anxiety disorders will be permitted. The diagnoses will be confirmed using the MINI-KID.

8. The participant has a CDRS-R total score greater than or equal to 45 at the Screening Visit and at the Baseline A Visit (Week 0).

9. The participant has a CGI-S score greater than or equal to4 at the Screening Visit and at the Baseline A Visit (Week 0).

10. The participant has a PHQ-A score of greater than or equal to10 at the Baseline A Visit (Week 0).

11. The participant, if a female and is capable of producing viable ova, agrees to the following, for the period from the signing of ICF until 30 days after the last dose of trial intervention.

    • To use a highly effective or acceptable contraceptive method
    • To avoid donating ova

12. The participant, if a female, must have a confirmed negative urine pregnancy test at the Screening Visit

Exclusion Criteria:

1. The participant has previously been entered and moved to Phase A in this trial.

2. The participant has participated in a clinical trial less than 30 days before the Screening Visit.

3. The participant is a member of the trial personnel or of their immediate families or is a subordinate (or immediate family member of a subordinate) to any of the trial personnel.

4. The participant has been previously treated with vortioxetine.

5. The participant has the current or previous major depressive episode which was considered by the investigators to have been resistant to 2 or more adequate antidepressants treatments of at least 6-weeks duration each at sufficient doses.

6. The participant is under forced treatment.

7. The participant has experienced any environmental change (eg, hospitalization, change of residence) considered by the investigator to have the potential impact on the participant's disease situation or plans such environmental changes during the trial.

8. The participant is pregnant or breast-feeding.

9. The participant receives on-going psychotherapy (except for a supportive psychotherapy) that is started less than 3 months before the Baseline A Visit (Week 0) and/or that is planned to be intensified during the trial.

10. The participant has a history of severe drug allergy or hypersensitivity or known hypersensitivity to any of the IMPs or their excipients.

11. The participant has hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltose insufficiency.

12. The participant has any current psychiatric disorder (DSM-5-TR criteria), including posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) established as the primary diagnosis, as assessed using the MINI-KID.

13. The participant has a medical history of substance use disorder (excluding nicotine, and caffeine) or alcohol use disorder (DSM-5-TR criteria) less than 6 months before the Screening Visit.

14. The participant has reported current use of or has tested positive for drugs of abuse (opiates, methadone, cocaine, amphetamines [including ecstasy], barbiturates, benzodiazepines, and cannabinoids, etc).

15. The participant suffers from medical, organic or drug cause mental disorders (DSM-5-TR criteria).

16. The participant has a known intellectual disability; or clinical evidence or known social or school history indicative of intellectual disability.

17. The participant has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with trial treatment or impair treatment compliance.

18. The participant has a history of moderate or severe head trauma; or other neurological disorders or systemic medical diseases that are, in the investigator's opinion, likely to affect central nervous system functioning.

19. The participant has a known first degree relative with a history of bipolar disorder.

20. The participant is unable to swallow tablets.

21. The participant has a history of cancer that has not been in remission for more than 5 years before the first dose of trial intervention.

22. The participant has or has had 1 or more of the following conditions that is/are considered clinically relevant in the context of the trial: neurological disorder, other psychiatric disorder, cardiovascular disease, seizure disorder or encephalopathy, congestive heart failure, cardiac hypertrophy, arrhythmia, bradycardia (pulse less than 50 bpm), respiratory disease, hepatic impairment or renal insufficiency, metabolic disorder, endocrinological disorder, gastrointestinal disorder, hematological disorder, infectious disorder, any clinically significant immunological condition, dermatological disorder, venereal disease, congenital or juvenile glaucoma or is at risk of acute narrow-angle glaucoma

23. The participant takes or has taken disallowed recent or concomitant medication, or it is anticipated that the participant will require treatment with at least one of the disallowed concomitant medications/procedures or treatment during the trial.

24. The participant has clinically significant abnormal vital signs at the Screening Visit.

25. The participant has 1 or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the Screening Visit, which are of potential risk to the participant's safety; or the participant has, at the Screening Visit:

    • a serum creatinine value more than 1.5 times the upper limit of the reference range
    • a serum total bilirubin value more than 1.5 times the upper limit of the reference range
    • a serum ALT or AST value more than 2 times the upper limit of the reference range

26. The participant has an abnormal TSH level. Participant with thyroid disease may be enrolled in the trial provided they are stable and euthyroid at the discretion of the investigator.

27. The participant has, at the Screening Visit:

    • an abnormal ECG that is, in the investigator's opinion, clinically significant
    • a QTcF interval more than 450 ms (based on the Fridericia correction where QTcF = QT/RR0.33)

28. The participant has a disease or takes medication that could, in the investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with the conduct or interpretation of the trial.

29. The participant is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.

30. The participant has attempted suicide within the last 12 months or is at significant risk of suicide (either in the opinion of the investigator or defined as a 'yes' to suicidal ideation questions 4 or 5 or answering 'yes' to suicidal behavior questions on the C-SSRS within the last 12 months).