| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD) |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025454 |
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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 compare the efficacy of the administration of sertraline and elzasonan combination (SEC) to sertraline monotherapy in the acute treatment of subjects with MDD as measured by Montgomery-Asberg Depression Rating Scale (MADRS) remission rates at Week 8. |
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| E.2.2 | Secondary objectives of the trial |
1. Conduct comparative analyses between treatment groups for MADRS, 17-item Hamilton Depression Rating Scale (HAMD17), Clinical Global Impression of Improvement (CGI-I), Clinical Global Impression of Severity (CGI-S), and Hamilton Anxiety Rating Scale (HAMA)
2. Characterize population pharmacokinetics in treatment groups
3. Evaluate effects on sexual functioning measured by Changes in Sexual Functioning Questionnaire (CSFQ)
4. Evaluate psychological health and functioning using Schwartz Outcomes Scale (SOS-10)
5. Evaluate safety and tolerability of SEC and sertraline monotherapy
6. Explore psychometric properties, including reliability, validity, and responsiveness of the Patient Global Impression - Dimensional (PGI-D)
7. haracterize the influence of the homozygous short/short (“SS”), long/long (“LL”), and heterozygous (“SL”) genotypes of the serotonin transporter gene promoter region on efficacy and safety variables in subjects with MDD
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Adult subjects, 18 years of age or older, with a diagnosis of recurrent, moderate-to-severe MDD without psychotic features (DSM IV 296.3x).
2. Subjects must have a HAMD17 score ≥22 and CGI-S score ≥4 at both the screening and Week 0 (baseline) visits.
3. Subjects must have a primary diagnosis of recurrent MDD without psychotic features by DSM IV criteria (296.3x) as confirmed by the M.I.N.I.. The current depressive episode must be at least 1 month in duration but no longer than 6 months in duration.
4. MDD must be the primary psychiatric disorder present and the condition that motivated the subject to seek treatment. Subjects with concurrent diagnoses of Dysthymic Disorder, Specific Phobia, or Social Phobia are eligible if MDD is the primary diagnosis. Subjects with a concurrent diagnosis of Generalized Anxiety Disorder (GAD) are eligible if MDD is the primary diagnosis and the current depressive episode began before GAD criteria were met.
5. Subjects must be in good health and have normal laboratory findings at screening, including thyroid function tests, except for minor divergences from normal ranges of laboratory tests determined to be clinically non-significant by the investigator.
6. Females of childbearing potential must be willing to use an acceptable method of contraception from at least 14 days prior to the Week 0 (baseline) visit until completion of follow-up procedures.
7. The subject's electrocardiogram must be without clinically significant abnormalities as determined by an internist and/or cardiologist at the screening visit.
8. Urine drug screen at screening should be negative for illicit drugs and/or protocol prohibited psychoactive substances; eg, benzodiazepines. Chronic benzodiazepine users are excluded from participating in the trial.
9. Subjects must have a Body Mass Index (BMI) of ≥17 and <35 and a body weight more than 40 kg (88 lbs) at screening. Minor BMI divergences in this range may be enrolled at the discretion of the investigator and upon discussion with the sponsor.
10. Subjects must have a normal neurological examination at screening, except for minor findings determined to be clinically insignificant by the investigator. |
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| E.4 | Principal exclusion criteria |
1. Investigators and their immediate families
2. Subjects who have ever been diagnosed with Panic Disorder, Post-Traumatic Stress Disorder (PTSD), Obsessive-Compulsive Disorder (OCD), Bipolar Affective Disorder, Schizophrenia, Schizoaffective Disorder or other Psychotic Disorder, MDD with Seasonal Pattern, or Dissociative Disorders per DSM-IV criteria. Subjects with current DSM-IV-defined Substance Abuse or Dependence
3. Subjects who have been treated with ECT or fluoxetine within 6 weeks prior to the baseline visit, who have been treated with monoamine oxidase inhibitors within 2 weeks prior to the baseline visit, any oral antipsychotics within 4 weeks prior to the baseline visit, any subjects who have previously used depot antipsychotics, and subjects who, in the investigator's judgment, would require treatment with electro-convulsive therapy, antipsychotics, would require a change in intensity of sychotherapy, or would require additional treatment with any other psychotherapeutic drugs during the trial
4. Subjects who have been treated with prescription or nonprescription psychotropic drug within 1 week prior to the baseline visit, with the exception of the protocol allowed concomitant medications
5. Subjects who have been treated with oral antipsychotics within 4 weeks prior to the baseline visit
6. Subjects who have previously participated in this trial or any other clinical trial with elzasonan or sertraline
7. Subjects with comorbid Personality Disorders (Axis II) based on DSM-IV criteria and the clinical judgment of the investigator
8. Subjects who are judged clinically to be at serious suicidal or homicidal risk
9. Subjects who in the judgment of the investigator are unable or unlikely to comprehend and/or follow the clinical trial protocol. Subjects must be able to provide and be competent to sign an informed consent form for participation in the study
10. Subjects who in the judgment of the investigator are unlikely to comply with trial medication
11. Female subjects who are pregnant or breastfeeding. Males and females unwilling to abstain from sex or comply with lifestyle guidelines in protocol
12. Subjects with a history of clinically significant and currently relevant hematological, renal (including single kidney), hepatic, gastrointestinal, endocrine, including diabetes type I and type II, pulmonary, dermatological, oncological, or neurological disease, including seizures or seizure disorders of any etiology
13. Subjects with uncorrected hypothyroidism or hyperthyroidism. Subjects requiring thyroid hormone replacement must be on a stable dose of medication for at least 2 weeks prior to the baseline visit
14. Subjects with a history of clinically significant cardiovascular disease, including hypertension, hypotension, any significant symptomatic arrhythmia, congestive heart failure, angina pectoris, cardiac bypass surgery, or recent (within the last 6 months) myocardial infarction
15. Subjects with ECG evidence of QRS >120 msec or QTc >450 msec. Additionally, subjects with clinically significant ECG abnormality at screening including conduction abnormalities or known history of QT prolongation (including congenital long QT syndrome)
16. Subjects known to be HIV positive
17. Subjects positive for hepatitis B surface antigen and/or hepatitis C antibody with liver function tests outside the normal range.
18. Subjects with known allergy to elzasonan or sertraline, or their excipients
19. Subjects with any medical condition that has a significant potential to alter the absorption of trial medication; e.g., gastrectomy or gastric bypass surgery
20. Subjects who have received treatment with any investigational drug within 4 weeks prior to the baseline visit
21. Subjects likely to be hospitalized for any reason during the clinical trial
22. Subjects who plan to donate blood during the trial period or during the one month after trial completion
23. Subjects currently taking any protocol prohibited concomitant medication
24. Subjects with clinically significant laboratory abnormalities at screening. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial
25. Subjects with a known failure to satisfactorily respond after adequate dose and duration (approximately 12 weeks) of treatment with sertraline, clomipramine and one SSRI, or with two or more SSRIs in the following approximate dose ranges.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Remission rate at Week 8, where remission is defined as a MADRS total score of ≤11. |
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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 | No |
| 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 | Information not present in EudraCT |
| 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.8.3 |
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 | No |
| 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 | 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
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 0 |
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