| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD) |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025454 |
| E.1.2 | Term | Major depressive disorder, recurrent episode |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the 52-week safety and tolerability of an oral aripiprazole/escitalopram combination therapy in the treatment of patients with MDD. |
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| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by IRB/IEC), prior to the initiation of any protocol-required procedures.
2. Ability, in the opinion of the principal investigator, to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet/capsule ingestion, and discontinuation of prohibited concomitant medication; to read and understand the written word in order to complete subject-reported outcomes measures; and to be reliably rated on assessment scales.
3. Male or female outpatients 18 to 66 years of age, inclusive, at the time of informed consent.
4. Subjects who have participated in Protocol 31-08-255, 31-08-256 or 31-08-263 and who, in the opinion of the investigator, could potentially benefit form the administration of oral aripiprazole/escitalopram combination therapy. Eligible subjects include those who:
a) completed participation in the Randomization Phase (Phase C, Week 14 Visit) or
b) met criteria for a response at the end of the Prospective treatment Phase (Phase B, Week 8 Visit) and at the end of Phase B+ (Week 14 Visit) did not meet criteria for remission (defined as a MADRS Total Score =<10). |
|
| E.4 | Principal exclusion criteria |
Sex and Reproductive Status
1. Sexually active males or females of childbearing potential who are not practicing two different methods of birth control during the study and for 90 or 30 days respectively after the last dose of study medication or who will not remain abstinent during the study and for 90 or 30 days respectively after the last dose. (*)
2. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug.
Target Disease
3. Subjects with a current need for involuntary commitment or who have been hospitalized <= 28 days of the Baseline Visit for the current major depressive episode.
4. Subjects with a current Axis I (DSM-IV-TR) diagnosis of any of the disorders listed in the protocol (*)
5. Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
6. Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode.
Medical History and Concurrent Diseases
7. Subjects with a significant risk of committing suicide based on history, investigator’s judgement, and/or evaluation based on the C-SSRS.
8. Subjects who have met DSM-IV-TR criteria for substance abuse in the past 6 months (prior to the Baseline Visit) and/or dependence up to and including the past 12 months (prior to Baseline Visit), including alcohol and benzodiazepines, but excluding caffeine and nicotine. (*)
9. Subjects with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least 90 days prior to the Baseline Visit). (*)
10. Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, haematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders. (*)
11. Subjects with insulin-dependant diabetes mellitus (IDDM) are excluded. Subjects with non-IDDM may be eligible for the study if their condition is stable as determined by satisfying ALL of the criteria in protocol. (*)
12. Subjects with epilepsy or significant history of seizure disorders, except a single childhood febrile seizure, posttraumatic, etc. An alcohol withdrawal seizure up to and including 24 months of the Baseline Visit is exclusionary.
Physical and Laboratory Results
13. Subjects with two positive drug screens for cocaine or other drugs of abuse (excluding stimulants and other prescribed medications and marijuana) (*)
14. The following laboratory test are exclusionary: Platelets =< 75,000/mm3; Hemoglobin =< 9 g/dL; Neutrophils, absolute =< 1000/mm3; AST > 3x upper limit of normal as defined by the central laboratory; ALT > 3x upper limit of normal as defined by the central laboratory; Creatinine >= 2 mg/dL; (*)
Prohibited Therapies or Medications
15. Subjects who would be likely to require prohibited prior or concomitant therapy during the trial (*)
16. Anticipated need for diphenylhydramine or hydroxyzine during the study and other antihistamines for the treatment of agitation, anxiety or insomnia.
Allergies and Adverse Drug Reactions
17. History of allergy or hypersensitivity to aripiprazole or escitalopram.
18. Subjects with a history of neuroleptic malignant syndrome or serotonin syndrome.
Other
19. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg. infectious disease) illness must not be enrolled into this study.
20. Any subject who, in the opinion of the investigator, should not participate in the study.
Note: Subjects who do not qualify for Protocol 31-08-257 at the last visit of Protocol 31-08-255, 31-08-256, 31-08-263 may not be rescreened.
* please see protocol for further information
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary outcome variable of safety will be the frequency and severity of AEs, including serious AEs (SAEs) and discontinuations from the study due to AEs. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Key secondary efficacy variables will include the mean Clinical Global Impression -
Severity of Illness Scale (CGI-S) score, and the mean Patient Global Impression of
Severity (PGI-S) score at baseline and at each time point.
In addition to AEs, safety variables examined in this study will include physical
examinations, vital signs, body weight, body mass index (BMI), clinical laboratory tests
(including, but not limited to, prolactin and hemoglobin A1c), electrocardiograms
(ECGs), the Abnormal Involuntary Movement Scale (AIMS), the Simpson Angus Scale
(SAS), the Barnes Akathisia Rating Scale (BARS), the Columbia-Suicide Severity Rating
Scale (C-SSRS), and the Massachusetts General Hospital Sexual Functioning Inventory
(MGH SFI).
Outcome variables will be evaluated for the mean Quality of Life Enjoyment and
Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) scores, the mean Sheehan Disability Scale (SDS) score, and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) score. Responses to the Resource Utilization Form will be summarized appropriately to explore the impact of treatment on health care resources.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Multiple timepoints (refer to Table 3.6.1 in the protocol for details) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 84 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Bulgaria |
| Canada |
| Croatia |
| Estonia |
| Finland |
| France |
| Germany |
| Hungary |
| India |
| Italy |
| Korea, Republic of |
| Malaysia |
| Mexico |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| Slovakia |
| South Africa |
| Spain |
| Sweden |
| Taiwan |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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