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

Inclusion Criteria:

1. The Japanese participant is a male or female, aged 12 to 17 years at the time ofinformed consent (patients who turn 18 years during the trial will be allowed tocontinue 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 andparent(s)/legal guardian(s) are able to read and understand the ICF. The participantis able and willing to accept video recording at the assessment by the trial siteand evaluation by third party evaluators (Central Evaluating Committee).

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

5. The participant and parent(s)/legal guardian(s) are willing and able to attend trialappointments 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 andfully meet the criteria for major depressive episodes according to DSM-5-TR withoutpsychotic features although co-morbid anxiety disorders will be permitted. Thediagnoses will be confirmed using the MINI-KID.

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

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

11. The participant, if a female and is capable of producing viable ova, agrees to thefollowing, for the period from the signing of ICF until 30 days after the last doseof 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 atthe 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 theScreening Visit.

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

4. The participant has been previously treated with vortioxetine.

5. The participant has the current or previous major depressive episode which wasconsidered by the investigators to have been resistant to 2 or more adequateantidepressants 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 onthe participant's disease situation or plans such environmental changes during thetrial.

8. The participant is pregnant or breast-feeding.

9. The participant receives on-going psychotherapy (except for a supportivepsychotherapy) 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 knownhypersensitivity to any of the IMPs or their excipients.

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

12. The participant has any current psychiatric disorder (DSM-5-TR criteria), includingposttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), autismspectrum 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 beforethe Screening Visit.

14. The participant has reported current use of or has tested positive for drugs ofabuse (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 knownsocial or school history indicative of intellectual disability.

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

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

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

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/areconsidered clinically relevant in the context of the trial: neurological disorder,other psychiatric disorder, cardiovascular disease, seizure disorder orencephalopathy, congestive heart failure, cardiac hypertrophy, arrhythmia,bradycardia (pulse less than 50 bpm), respiratory disease, hepatic impairment orrenal insufficiency, metabolic disorder, endocrinological disorder, gastrointestinaldisorder, hematological disorder, infectious disorder, any clinically significantimmunological condition, dermatological disorder, venereal disease, congenital orjuvenile glaucoma or is at risk of acute narrow-angle glaucoma

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

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

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

• a serum creatinine value more than 1.5 times the upper limit of the referencerange

• a serum total bilirubin value more than 1.5 times the upper limit of thereference range

• a serum ALT or AST value more than 2 times the upper limit of the referencerange

26. The participant has an abnormal TSH level. Participant with thyroid disease may beenrolled in the trial provided they are stable and euthyroid at the discretion ofthe 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'sopinion, interfere with the assessments of safety, tolerability, or efficacy, orinterfere with the conduct or interpretation of the trial.

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

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