| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Insomnia
Major Depressive Disorder |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025453 |
| E.1.2 | Term | Major depressive disorder NOS |
|
| 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 antidepressant effect of adjunctive treatment with Eszopiclone in subjects receiving venlafaxine for the treatment of Major Depressive Disorder (MDD) |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate subjective sleep efficacy in subjects with insomnia related to Major Depressive Disorder |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Initial Inclusion Criteria:
1. Subject is capable of understanding and complying with the protocol. Subject has signed the informed consent document.
2. Subject is a male or female between 18 and 64 years of age, inclusive, at the time of signing consent.
3. If subject is female, subject is:
(a) of non-childbearing potential and is at least two years postmenopausal or surgically sterile. If under the age of 55, subject has a negative serum pregnancy test (beta-HCG) at screening. -OR-
(b) of childbearing potential and has signed the Women of Childbearing Potential Addendum to the informed consent form. Subject is not pregnant as demonstrated by a negative serum pregnancy test (beta-HCG) at screening or nursing, is practicing effective contraception and meets all of the following criteria: (1) Is instructed to and agrees to avoid pregnancy during the study. (2) Uses one of the birth control methods listed below: a. an oral contraceptive agent, an intrauterine device (IUD), implantable contraceptive, transdermal or injectable contraceptive for at least one month prior to entering the study and will continue its use throughout the study and for thirty days following study participation. b. barrier method of contraception, e.g., condom and/or diaphragm with spermicide while participating in the study.
Psychiatric Inclusion Criteria:
Note: At screening, a complete psychiatric interview will be performed by a qualified psychiatrist. The Axis I psychiatric inclusion and exclusion criteria and Axis II (Personality Disorders) psychiatric exclusion criterion will be based on the results of this interview. The semi structured Mini International Neuropsychiatric Interview (M.I.N.I.) (Sheehan et al. 1997, 1998) will be performed by a trained rater as confirmation of the Axis I diagnosis.
1. Subject has a primary diagnosis of Major Depressive Disorder (MDD) by DSM-IV criteria (MDD; 296.XX), moderate (296.X2) or severe depression without psychotic features (296.X3) with the presences of either a single episode (296.2X) or recurrent episode (296.3X) as determined by the clinical interview.
2. Subject’s symptoms of depression have been present for at least 1 month before screening, but not longer than 6 months in duration.
3. MDD is the condition that was primarily responsible for motivating the subject to seek treatment.
4. Subject has score of ≥ 22 on the 17-item Hamilton Depression Scale (HAM-D-17) at screening.
5. Subject is deemed appropriate by the investigator for medical treatment with venlafaxine for depression.
Medical Inclusion Criteria:
1. Subject meets DSM IV criteria for insomnia related to MDD, and the symptoms of insomnia do not pre–date the symptoms of MDD by more than 10 weeks.
2. Subject reports a total sleep time of ≤ 6.5 hours at least three times per week over the past month.
3. Subject is in general good health (defined as the absence of any clinically relevant abnormalities), based on the screening physical examination and medical history.
4. The subject's electrocardiogram has no clinically significant abnormalities at screening. Subjects with any significant, symptomatic or asymptomatic arrhythmia, including first (PR interval > 220 msec), second or third degree heart block will not be permitted to enter the study.
5. Subject has a normal neurological examination at screening.
6. Subject has a negative urine drug and alcohol test at screening.
7. Subject is able to remain free of any prescription or nonprescription psychotropic drugs for two weeks prior to baseline (six weeks in the case of neuroleptics). |
|
| E.4 | Principal exclusion criteria |
Initial Exclusion Criteria:
1. Subject is participating in, has participated in, or plans to participate in any investigational drug study within 30 days prior to screening until 30 days following the end of participation in this study.
2. Subject has a known sensitivity to zopiclone, eszopiclone or venlafaxine or are known to have failed previous zopiclone, eszopiclone or venlafaxine treatment.
3. Subject has history of circadian rhythm disorder, travels across ≥ 3 times zones on a regular basis, or is a rotating or third/night shift worker.
4. Subject is unwilling to refrain from drinking alcoholic beverages during study participation.
5. Subject is a staff member or relative of a staff member.
6. Subject has used any drugs as outlined in Section 11.1 in protocol 190-096(Disallowed Medications) within 1 week of Visit 1.
Psychiatric Exclusion Criteria:
1. Subject’s depression, in the opinion of the investigator, is so severe that hospitalization is required.
2. Subject has failed to respond (in past 5 years) to more than one adequate antidepressant therapy including tricyclics (e.g. imipramine 150 mg/day for 6 weeks or equivalent) and SSRIs (e.g. fluoxetine 20 mg/day for 6 weeks or equivalent) and SNRIs (e.g. duloxetine 60mg/day for 6 weeks or equivalent).
3. Subject, in the Investigator’s judgment, would require electroconvulsive therapy (ECT) or treatment with additional psychotherapeutic drugs including lithium, and neuroleptics.
4. Subject has received treatment for depression (adequate duration and dose including ECT) in the past six months.
5. Subject requires an introduction, or change in intensity, of psychotherapy (including behavioral therapies) from 3 months prior to the baseline visit through the duration of the study. (Note: Non-directive counseling associated with the prescription/administration of study medication and attendance at Alcoholics Anonymous meetings is permitted during the trial.)
6. Subject recieved treatment with fluoxetine, neuroleptics, or ECT in the 6 weeks before baseline, or other antidepressants within 2 weeks prior baseline.
7. Subject has current (within 6 months prior to baseline) DSM-IV-defined Psychoactive Substance (including alcohol) Abuse or Dependence or has a positive urine drug or alcohol screen at Visit 1.
8. Subject has a current (within 6 month prior to baseline) primary DSM-IV Axis I psychiatric diagnosis of any of the following disorders: dementia, delirium, schizophrenia, psychosis, other psychotic disorders, dysthymic disorder; bipolar disorders; cyclothymic disorder, other mood disorders, nocturnal panic disorder, primary anxiety disorders, primary panic disorders or any other psychiatric disorder that would compromise the investigator’s ability to evaluate the safety and efficacy of the study medication.
9. Subject has any of the following DSM IV Axis II Personality Disorders diagnoses: schizotypal, schizoid, borderline personality disorder; mental retardation or any other personality disorder that would compromise the investigator’s ability to evaluate the safety and efficacy of the study medication.
10. Subject has a history of significant risk of suicide or homicide, or is considered at risk for suicide or homicide during the study. (Based on interview or HAM-D17 item 3 score ≥ 2)
Medical Exclusion Criteria
1. Subject has a documented history of HIV, hepatitis B or hepatitis C.
2. Subject has a history of clinically significant and currently relevant or active hematological, renal (including single kidney), hepatic, gastrointestinal, endocrine, pulmonary, dermatological, oncological, or neurological disease, including all forms of seizures, including febrile seizures, and epilepsy.
3. Subject has a disorder or history of a condition (e.g., malabsorption, gastrointestinal surgery) that may interfere with drug absorption, distribution, metabolism, or excretion.
4. Subject has used any drugs known or suspected to affect hepatic or renal clearance capacity within a period of 30 days prior to screening.
5. Subjects has a history of significant cardiovascular disease, including uncontrolled hypertension (as defined above), hypotension, first (PR greater than 220msec), second, or third degree heart block, congestive heart failure, angina pectoris, bypass surgery, angioplasty, or recent myocardial infarction (within the last 6 months).
6. Subject is likely to be hospitalized (for any reason) during the study.
7. Subject has another primary sleep disorder (e.g., sleep apnea, restless leg syndrome, or periodic limb movement disorder), or has another secondary sleep disorder (any other known or suspected medical or psychiatric condition that has or may affect sleep (e.g., chronic pain, benign prostatic hypertrophy).
8. Subject is using beta blockers for psychiatric reasons or is not on a stable dose for any condition for a minimum of 30 days prior to the Visit 1. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is a change from baseline in HAM-D-17 total score at 8 weeks |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| 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 | 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 6 |
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