E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Major Depressive Disorder with an Inadequate Response to Antidepressant Therapy. |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
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 | 10025453 |
E.1.2 | Term | Major depressive disorder NOS |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
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 evaluate the efficacy of TC-5214 compared with placebo in patients with major depressive disorder (MDD) who exhibit an inadequate response to SSRI/SNRI therapy, as assessed by change in MADRS total score from Week 8 (baseline) to end of treatment (Week 16).
|
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of TC-5214 compared with placebo in patients with MDD
who exhibit an inadequate response to SSRI/SNRI therapy as assessed by
depressive symptoms, clinical global outcome regarding severity and improvement and anxiety.
• To evaluate the efficacy of TC-5214 compared with placebo in patients with MDD who exhibit an inadequate response to SSRI/SNRI therapy as assessed by patient reported outcomes (PROs) regarding functional impairment.
• To investigate pharmacokinetic (PK) properties of TC-5214 in patients with MDD using a population PK analysis methodology. SSRI/SNRI compliance will be
quantified in the open-label period. The PK properties of TC-5214 using
population PK analysis methodology will be investigated and reported separately
from the Clinical Study Report (CSR).
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics Research. Version 1.0, date 11 Nov 2010
AstraZeneca intends to perform genetic research in the TC5214 clinical development programme to explore how genetic variations may affect the clinical parameters associated with TC 5214 and/or agents used in combination or as comparators. Collection of DNA samples from populations with well described clinical characteristics may lead to improvements in the design and interpretation of clinical trials and, possibly, to genetically guided treatment strategies. Studies may also be performed on the underlying genetic contribution to MDD.
The objective of this research is to collect and store DNA for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to TC 5214 and/or agents used in combination and/or as comparators. Investigations into the genetic factors influencing disease (depression) may also be undertaken. |
|
E.3 | Principal inclusion criteria |
1. Provision oof signed and dated informed consent before initiation of any study related procedures. 2. Male or female patients aged 18 to 65 years, inclusive. 3. The patient must have a clinical diagnosis of major depressive disorder (MDD) with inadequate response to no more than one antidepressant.
4. Women of child-bearing potential must have a negative urine pregnancy test and confirmed use of a highly effective form of birth control before enrollment and until 3 months after their last dose of study drug. 5. Outpatient status at enrollment and randomization. |
|
E.4 | Principal exclusion criteria |
1. Patients with a lifetime history of bipolar disorders; psychotic disorder or post-traumatic stress disorder.
2. Patients with a history of suicide attempts in the past year and/or seen by the investigator as having a significant history of risk of suicide or homicide.
3. Patients with any significant unstable hepatic, renal, pulmonary, cardiovascular, ophthalmologic, neurologic, or any other medical conditions that might confound the study or put the patient at greater risk during study participation. 4. History of stroke or transient ischemic attack, seizures or seizure disorder, head trauma including closed head injury. 5. Pregnancy or lactation.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measures: Change in the MADRS total score from randomization(Week 8) to end of treatment (Week 16). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Will be scored at Weeks 8 (baseline), 9, 10, 12, 14, 16. |
|
E.5.2 | Secondary end point(s) |
1. Changes in clinician rated symptoms as assessed by MADRS, Hamilton Rating Scale for Depression (HAMD), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I) and Hamilton Anxiety Assessment (HAM-A).
2. Changes in patient-reported outcomes as assessed by Sheehan Disability Scale (SDS), European Quality of Life (EQ-5D).
3. AE’s (any incidence) and SAE’s, will be assessed as a measure of safety and tolerability.
4. Change in physical exam results, vital signs, laboratory tests, ECG (electrocardiogram), and C-SSRS (Columbia Suicide Severity Rating Scale), CSFQ (Changes Sexual Functioning Questionnaire) and DESS (Discontinuation Emergent Signs and Symptoms) will be assessed as a measure of safety and tolerability. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. MADRS and CGI will be scored at Weeks 8 (baseline), 9, 10, 12, 14, 16.
HAM-D scored at weeks 8 (baseline), 12, and 16. HAM-A scored at weeks 8 (baseline) and 16.
2. SDS and EQ-5D will be scored at weeks 8 (baseline) and 16.
3. Collected weekly from the beginning of the screening period through Week 18. Unsolicited SAE’s will be collected from 30 days post last study treatment.
4. Routine safety monitoring from consent to withdrawal. |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Estonia |
Finland |
India |
Japan |
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
|
The end of the study is defined as “the last visit of the last patient undergoing the study”. The end of study definition is for the entire study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |