Long-Term Extension Study of Lu AA21004 in Participants With Major Depressive Disorder
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).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Number of Participants Reporting One or More Treatment-emergent Adverse Events [ Time Frame: 52 Weeks. ] [ Designated as safety issue: Yes ]Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.
- Number of Participants With Markedly Abnormal Laboratory Values [ Time Frame: Up to week 52. ] [ Designated as safety issue: Yes ]The number of participants with any markedly abnormal standard safety laboratory values collected at weeks 4, 12, 24, 36, 48 and 52 relative to baseline.
- Significant Change from Baseline in Body Weight [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. ] [ Designated as safety issue: Yes ]Change from baseline in participant's weight measured throughout study.
- Change from Baseline in Vital Signs [ Time Frame: 52 Weeks. ] [ Designated as safety issue: Yes ]Vital signs will include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
- Change from Baseline in Electrocardiograms [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. ] [ Designated as safety issue: Yes ]Change from baseline in electrocardiograms measured throughout study.
- Clinically Significant Change From Baseline in Physical Examination Findings [ Time Frame: 52 Weeks. ] [ Designated as safety issue: Yes ]Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10).
- Change from Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at each time point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. ] [ Designated as safety issue: No ]The change between MADRS score at week 8 or final visit relative to baseline. MADRS is a 10-item clinician rated scale that measures overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.
- Change from Baseline in the Clinical Global Impression Scale-Severity (CGI-S) score at each time point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. ] [ Designated as safety issue: No ]The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill). Higher scores indicate greater severity of illness.
- Change from Baseline in the Clinical Global Impression - Improvement (CGI-I) score at each time point [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. ] [ Designated as safety issue: No ]The CGI-I assesses the clinician's impression of the subject's state of mental illness improvement and consists of one question for the investigator: "Compared to his condition at the start of the study, how much has this patient changed?" which is rated on a seven-point scale (1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; 7=very much worse). Higher scores indicate greater severity of illness.
|Study Start Date:||July 2011|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Experimental: Lu AA21004 group||
Drug: Lu AA21004
Lu AA21004 10 mg, tablets, orally, once daily for 2 weeks; reduced to 5 mg or increased to 20 mg, once daily if necessary according to the responses and symptoms of participants for up to 50 weeks.
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.
|Inzai-shi, Chiba, Japan|
|Noda-City, Chiba, Japan|
|Fukuoka-city, Fukuoka, Japan|
|Kitakyushu-shi, Fukuoka, Japan|
|Annaka-shi, Gunma, Japan|
|Fujioka-shi, Gunma, Japan|
|Takasaki-shi, Gunma, Japan|
|Hatsukaichi-shi, Hiroshima, Japan|
|Hiroshima-shi, Hiroshima, Japan|
|Sapporo-Shi, Hokkaido, Japan|
|Amagasaki-shi, Hyogo, Japan|
|Kobe-shi, Hyogo, Japan|
|Fujisawa-shi, Kanagawa, Japan|
|Kawasaki-shi, Kanagawa, Japan|
|Sagamihara-shi, Kanagawa, Japan|
|Yokohama-shi, Kanagawa, Japan|
|Osaka-shi, Kita-ku, Japan|
|Kumamoto-shi, Kumamoto, Japan|
|Kyoto-shi, Kyoto, Japan|
|Kurashiki-shi, Okayama, Japan|
|Osaka-shi, Osaka, Japan|
|Fukaya-shi, Saitama, Japan|
|Saitama-city, Saitama, Japan|
|Utsunomiya-shi, Tochigi, Japan|
|Anan-shi, Tokushima, Japan|
|Tokushisma-shi, Tokushima, Japan|
|Hachioji-shi, Tokyo, Japan|
|Katsushika-ku, Tokyo, Japan|
|Musashino-shi, Tokyo, Japan|
|Nanyo-shi, Yamagata, Japan|
|Study Director:||Senior Director||Takeda|