E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The desvenlafaxine succinate sustained release formulation, DVS SR, is being used in development programs for the treatment of major depressive disorder (MDD). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025453 |
E.1.2 | Term | Major depressive disorder NOS |
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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 |
The primary objective is to compare the long-term efficacy and safety of treatment with DVS SR 50 mg/day versus placebo in MDD subjects stabilized on DVS SR, using a randomized withdrawal design. This comparison will be based on time to relapse between DVS SR and placebo treatment groups. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the long-term response of subjects receiving 50 mg/day of DVS SR versus placebo through clinical global assessments, remission (Hamilton Psychiatric Rating Scale for Depression, 17-item [HAM-D17] ≤ 7) and functional and quality of life outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Open-Label Phase, Screening/Baseline 1. Male or female subjects aged 18 years or older. 2. Outpatient status. 3. A primary diagnosis of MDD, single or recurrent episode, without psychotic features. 4. Depressive symptoms for at least 30 days before the screening visit. 5. A HAM-D17 total score ≥20 at the screening visit. 6. A score ≥2 on item 1 (depressed mood) of the HAM-D17 at the screening visit. 7. A score ≥4 on the Clinical Global Impressions Scale-Severity (CGI-S) at the screening visit. Stability Phase 1. Response to treatment, as defined as a HAM-D17 total score of ≤ 11 at the conclusion of the 8-week open-label phase. 2. A CGI-I score ≤ 2 at the conclusion of the 8-week open-label phase. Double-Blind Phase 1. Maintenance of stability, as defined as a HAM-D17 total score of ≤ 11 at the conclusion of the 12-week stability phase 2. CGI-I score ≤ 2 at the conclusion of the 12-week stability phase 3. Absence of an assessed HAM-D17 total score of ≥ 16 or CGI-I score of ≥ 4 at any visit during the stability phase..
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E.4 | Principal exclusion criteria |
Open-Label Phase, Screening 1. Treatment with DVS SR at any time in the past. 2. Known or suspected allergy to venlafaxine. 3. Significant risk of suicide based on clinical judgment. 4. HAM-D17 score > 3 on Item 3 (Suicide) at the screening visit. 5. Columbia Suicide-Severity Rating Scale (C-SSRS) determination of “yes” on question 4 or question 5 for the Suicidal Ideation section at the screening visit. 6. Pregnant or breastfeeding women. 7. a) Current psychoactive substance abuse or dependence, manic episode, posttraumatic stress disorder, obsessive compulsive disorder, or a lifetime diagnosis of bipolar or psychotic disorder; b) current generalized anxiety disorder, panic disorder, or social anxiety disorder considered by the investigator to be primary; c) presence of a clinically important personality disorder. 8. Depression associated with the presence of an organic mental disorder due to a general medical condition or a neurologic disorder. 9. History of seizure disorder other than a single childhood febrile seizure. 10. Any major illness/condition. 11. History or current evidence of gastrointestinal disease known to interfere with the absorption or excretion of drugs or a 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 cell or squamous cell carcinoma of the skin. 13. Known presence of raised intraocular pressure or history of narrow angle glaucoma. 14. Major acute illness within 90 days of the screening visit. 15. Myocardial infarction within 180 days of the screening visit. Open-Label Phase, Baseline 1. Clinically important abnormalities indicated by electrocardiograms (ECG), vital signs, laboratory tests or urine drug screening. 2. HAM-D17 score >3 on Item 3 (Suicide) at the baseline visit. 3. Columbia Suicide-Severity Rating Scale (C-SSRS) determination of “yes” on question 4 or question 5 for the Suicidal Ideation section at the baseline visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time to relapse following randomization to the double-blind phase. Relapse is defined as the occurrence of one or more of the following at any time during the double-blind phase: • HAM-D17 total score of ≥ 16 at any visit • discontinuation for unsatisfactory efficacy response • hospitalization for depression • attempted or completed suicide
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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 | 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) | No |
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.8.4.1 | 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 | 50 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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The end of the study is the last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |