Long-Term Extension Study of Lu AA21004 in Participants With Major Depressive Disorder

An Open-label, Long-Term Extension Study to Assess the Safety and Efficacy of Lu AA21004 in Patients With Major Depressive Disorder (Extension to Lu AA21004/CCT-003 Study)

The purpose of this study is to assess the safety and efficacy of Lu AA21004 in participants with major depressive disorder after completion of an 8-week double-blind treatment period in a preceding study (Lu AA21004/CCT-003; NCT01355081).

Lu AA21004 was discovered by H. Lundbeck A/S, and is under co-development by H. Lundbeck A/S and Takeda for the treatment of major depressive disorder and general anxiety disorder.

Major depressive disorder (MDD) is a chronic, recurring disease with considerable morbidity in the general population. The estimated lifetime prevalence of major depression in the adult population is 5 to 25%, with approximately 2-fold higher prevalence in women than in men. The hallmark of the disease is a depressed mood, with additional symptoms including sleep disturbances, psychomotor agitation or retardation, sexual dysfunction, weight loss, concentration difficulties and delusional ideas. In addition to direct ill effects, MDD causes suicide or job loss and exerts indirect influence on social economy.

This long-term extension study will assess the safety and efficacy of 52-week treatment with Lu AA21004 in participants with major depressive disorder after completion of the 8-week double-blind treatment period in the preceding study (LuAA21004/CCT-003; NCT01355081; hereinafter referred to as CCT-003). This study will be conducted at the same institutions as CCT-003.

This study will include participants who completed the 8-week double-blind treatment period in CCT-003, and who meet all of the inclusion criteria, and do not meet any of the exclusion criteria of the long-term study. Visit 1 in this study will be the last visit (Visit 7) during the 8-week double-blind treatment period in CCT-003. Participants will start 2-week treatment with 10 mg/day of Lu AA21004 on the day after completion of the 8-week double-blind treatment period in CCT-003. The dose may then be decreased to 5 mg/day or increased to 20 mg/day according to the responses and symptoms of the participants. A dose increase, however, will be allowed only if the Clinical Global Impression (CGI) score meets the criteria for dose increases and the investigator or sub-investigator considers it necessary to increase the dose. The same dose should be maintained for at least 2 weeks after a dose change, except when immediate dose reduction is required for safety reasons. Neither dose increase from 5 to 20 mg nor dose reduction from 20 to 5 mg will be allowed.

The duration of administration will be 52 weeks. Participants will visit the study site every 2 weeks during the first month of treatment and every 4 weeks thereafter (Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52). Participants will be followed up 4 weeks after the last dose of the study drug, and those who prematurely discontinue the study will also be followed up 4 weeks after the last dose, whenever possible.

Inclusion Criteria:

1. Has completed the double-blind treatment period of the preceding study (CCT-003)
2. Signs and dates a written, informed consent form for this study, different from that for the preceding study (CCT-003).
3. Has CGI-S score improved at least one point at completion of the 8-week double-blind treatment period compared to the Baseline Visit in the preceding study (CCT-003).
4. In the opinion of the investigator, the subject appears to benefit from long-term treatment of Lu AA21004.

Exclusion Criteria:

1. Diagnosed with the following disorder or symptom in the preceding study (CCT-003):

   • Any current psychiatric disorder other than MDD as defined in a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR).
   • Any substance-related disorder (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR.
   • Clinically significant neurological disorder (including epilepsy).
   • Neurodegenerative disorder (Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, etc.).
   • Any DSM-IV-TR axis II disorder that might compromise this study.

2. Is at significant risk of suicide, or had a score ≥5 on Item 10 (suicidal thoughts) of the MADRS or attempted suicides during the preceding study (CCT-003)