| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major depressive disorder |
|
| MedDRA Classification |
| 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 |
| The study objective is to compare the antidepressant efficacy and safety of DVS-233 SR with those of placebo in adult outpatients with MDD. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Outpatients.
2. Men and women 18 to 75 years of age, inclusive.
3. Women of child-bearing potential participating in the study must have a negative serum pregnancy test at screening and use a medically acceptable form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used double-barrier contraception, eg condom plus diaphragm.
4. Subjects must have a primary diagnosis of major depressive disorder (MDD) based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), single or recurrent episode, without psychotic features. If other allowable psychiatric diagnoses are present, MDD must be the predominant psychiatric disorder present. (See Exclusion Criterion 6 for other psychiatric diagnoses that are not allowable.)
5. Depressive symptoms for at least 30 days before the screening visit.
6. Minimum screening and study day –1 (baseline) scores of 22 on the Hamilton Psychiatric Rating Scale for Depression (HAM-D17).
7. Minimum screening and study day –1 (baseline) scores of 2 on item 1 (depressed mood) of the Hamilton Psychiatric Rating Scale for Depression (HAM-D17).
8. Minimum screening and study day –1 (baseline) scores of 4 on Clinical Global Impressions-Severity scale (CGI-S).
9. Signed and dated informed consent before any screening procedures. |
|
| E.4 | Principal exclusion criteria |
1. Treatment with DVS-233 SR at any time in the past.
2. Treatment with venlafaxine (immediate release [IR] or extended release [ER]), within 90 days of study day 1.
3. Known hypersensitivity to venlafaxine (IR or ER).
4. Significant risk of suicide based on clinical judgment. Common suicidal thoughts, and suicide being considered as a possible solution, even without specific plans or intention.
5. Women who are pregnant, breastfeeding, or planning to become pregnant during the study.
6. Current (within 12 months of baseline) psychoactive substance abuse or dependence (including alcohol), manic episode, posttraumatic stress disorder, obsessive-compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder as assessed by the modified Mini International Neuropsychiatric Interview (MINI). Current (within 12 months of baseline) generalized anxiety disorder, panic disorder, or social anxiety disorder as assessed by the modified MINI and considered by the investigator to be primary, causing a higher degree of distress or impairment than MDD. Presence (within 12 months of baseline) of a clinically important personality disorder (such as antisocial, schizotypal, histrionic, borderline, narcissistic).
7. A Covi Anxiety Scale total score greater than the Raskin Depression Scale total score at screening or at study day –1 (baseline). A Covi Anxiety score greater than 3 on any single item or a total score greater than 9 at screening or at study day -1 (baseline).
8. Depression associated with the presence of an organic mental disorder due to a general medical condition or a neurological disorder.
9. History of a seizure disorder other than a single childhood febrile seizure.
10. History or presence of clinically important hepatic or renal disease or other medical disease that might confound the study or be detrimental to the subject (eg, clinically important cardiac arrhythmia, uncontrolled diabetes, uncontrolled hypertension).
11. History or current evidence of gastrointestinal disease known to interfere with the absorption or excretion of drugs or history of surgery known to interfere with the absorption or excretion of drugs.
12. History of neoplastic disorder (within 2 years), with the exception of basal or squamous cell carcinoma of the skin.
13. Known presence of raised intraocular pressure or history of narrow-angle glaucoma.
14. Major acute illness during the 90 days before screening.
15. Myocardial infarction within 180 days before screening.
16. Clinically important abnormalities on screening physical examination, electrocardiogram (ECG), or laboratory tests. Clinically important abnormalities on screening urine drug screen (UDS), or a positive test result for tetrahydrocannabinol (THC), illicit opioids, or cocaine.
17. Use of prohibited treatments. Refer to the table that follows, Excluded Treatments sections 16.1 and 16.2 (Permitted Treatment and Prohibited Treatment) for treatments and associated time frames. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary analysis will be the change from baseline on the HAM-D17 score at the final evaluation and will be done by using analysis of covariance (ANCOVA) with treatment and country as factors and baseline HAM-D17 scores as the covariate. A second model with treatment-by-country interaction will be investigated to explore the possibility of qualitative or quantitative treatment-by-country interaction. If the interaction is found to be significant (p ≤ 0.10), an assessment of the magnitude and directions will be made. In the absence of significant interaction, the interaction term for the model will be dropped. |
|
| 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 | No |
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
|
For those patients not eligible for continuation into the long-term extension protocol (3151A1-303), end of the study will be last patient visit.
For those patients eligible to enter the long-term extension protocol (3151A1-303) end of the trial will be day 56 visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 13 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 13 |
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