| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Patients with Major Depressive Disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR; APA
2004), |
|
| 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 |
|
| 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 assess whether LY2216684 is superior to placebo in the treatment of
patients with MDD, as defined by the Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR; APA
2004), during a 10-week, double-blind, acute treatment phase. Superiority
is defined as a statistically greater reduction in depressive symptoms from
baseline to endpoint as measured by the 16-Item Quick Inventory of
Depressive Symptomatology-Self Rated (QIDS-SR16) total score. |
|
| E.2.2 | Secondary objectives of the trial |
To assess whether LY2216684 is superior to placebo in the acute
treatment of patients with MDD in improving global function as measured
by change from baseline to endpoint in the Sheehan Disability Scale
(SDS) Global Functional Impairment score (Sheehan 1983).
|
|
| 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 |
1) Protocol Sample Storage Addendum H9P-MC-LNBI: A Randomized, Double-Blind Comparison of LY2216684 and Placebo and Long Term Treatment with LY2216684
in Adult Patients with Major Depressive Disorder.
Protocol Addendum (1)(a) Approved by Lilly: 19 September 2008
The primary objective of this addendum is to collect and store sample(s) of whole blood, plasma and serum for future research. The research on stored samples from this study will involve looking at genetic variants in deoxyribonucleic acid (DNA), proteins, or other biochemical markers associated with major depressive disorder (MDD) and treatment with LY2216684. Plasma may be analyzed for neurotransmitters and related precursors and metabolites including, but not limited to, norepinephrine (NE) and other biogenic amines and amino acid tranmitters, as well as dihydroxyphenylglycol (DHPG) and other biomarkers of transmitter turnover. DNA samples may be analyzed for genetic variants (polymorphisms and/or single nucleotide polymorphism [SNPs]) that include, but are not limited to, serotonin transporter (5-HTT), norepinephrine transporter (NET), adrenergic receptors, and genes associated with drug metabolism and transport.
2)Protocol Sample Banking Addendum H9P-MC-LNBI: A Randomized, Double-Blind Comparison of LY2216684 and Placebo and Long Term Treatment with LY2216684
in Adult Patients with Major Depressive Disorder.
Protocol Addendum (2)(a) Approved by Lilly: 19 September 2008
Rationale for Addendum: Collection of Biological Samples for Banking, Eli Lilly and
Company Sample Banking Program.
Eli Lilly and Company has established a program, Combined Specimen Banking (CSB),
to bank samples (collectively called Banked Samples) from subjects enrolled in studies sponsored by Eli Lilly and Company. The Banked Samples are collected and banked for research to identify the genes and/or gene products and/or biochemical markers associated with diseases and/or response to clinical trial medication or other medication taken during the trial. For example, in Study H9P-MC-LNBI, genes and/or gene products related to LY2216684 and/or major depressive disorder. |
|
| E.3 | Principal inclusion criteria |
Adult men or women at least 18 to 65 years of age at informed
consent, who provide informed consent by signing the appropriate
ICDs. Patients must be competent and able to give their own
informed consent.
[2] Meet criteria for MDD as defined by DSM-IV-TR criteria without
psychotic features, as determined by clinical assessment and
confirmed by the MINI at Visit 1. Have had at least one other major
depressive episode prior to the current episode.
[3] Women of child-bearing potential (not surgically sterilized and
between menarche and 1 year postmenopause) may participate in the
study. Women must test negative for pregnancy at the time of
enrollment based on a serum pregnancy test and agree to use a reliable
method of birth control (for example, use of oral contraceptives; a
reliable barrier method of birth control [diaphragms with contraceptive
jelly; cervical caps with contraceptive jelly; condoms with
contraceptive foam; intrauterine devices]; partner with vasectomy; or
abstinence) during the study.
[4] Have a GRID-HAMD17 total score ≥18 at Visit 1 and Visit 2.
[5] Have a CGI-Severity score ≥4 at Visit 1 and Visit 2.
[6] Have an education level and a degree of understanding such that the
patient can communicate with the site study personnel.
[7] Judged to be reliable and agree to keep all appointments for clinic
visits, tests, and procedures, including venipuncture, and examinations
required by the protocol. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
* Have previously completed or withdrawn from this study or any other
study investigating LY2216684.
* Have had or currently have any additional ongoing DSM-IV-TR Axis I
condition other than major depression that was considered the primary
diagnosis within 1 year of Visit 1.
*Have had any anxiety disorder preceding the onset of depression that
was considered a primary diagnosis within the past year (including
panic disorder, obsessive-compulsive disorder, posttraumatic stress
disorder, generalized anxiety disorder, and social phobia, but
excluding specific phobias).
*Have an Axis II disorder which, in the judgment of the investigator,
would interfere with compliance with the study protocol.
*Have a current or previous diagnosis of Bipolar I or II Disorder,
psychotic depression, schizophrenia, or other psychotic disorder
*Women who are pregnant or breast-feeding.
*Have had a lack of response of the current depressive episode to 2 or
more adequate courses of antidepressant therapy at a clinically
appropriate dose for at least 4 weeks, or in the judgment of the
investigator, the patient has treatment-resistant depression.
*Patients who, in the opinion of the investigator, are judged to be at
serious risk for harm to self or others.
*Have any diagnosed medical condition which could be exacerbated by
noradrenergic agents including unstable hypertension or unstable heart
disease, tachycardia or tachyarrhythmia, narrow angle glaucoma, or
urinary hesitancy or retention.
*Have received treatment with a monoamine oxidase inhibitor within
14 days prior to Visit 1 or have a potential need to use a monoamine
oxidase inhibitor within 14 days after discontinuation from the study.
*Have received treatment with fluoxetine within 30 days prior to
Visit 2.
*Have a history of electroconvulsive therapy (ECT), transcranial
magnetic stimulation (TMS), or psychosurgery within the last year
*Have a history of any seizure disorder (other than febrile seizures).
*Require psychotropic medication other than sedative/hypnotic
medication for sleep as specified in the protocol.
*Have a thyroid stimulating hormone (TSH) level outside the laboratory
established reference range. Patients previously diagnosed with
hyperthyroidism or hypothyroidism who have been treated with a
stable dose of thyroid supplement for at least the past 3 months, and
who are clinically and chemically euthyroid, will be allowed to
participate in the study.
*Have initiated or discontinued hormone therapy within the previous
3 months prior to enrollment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Baseline is defined as the last measurement taken at, or prior to, randomization (Visit 2); endpoint is defined as the last nonmissing measurement taken in
Study Period II (at or before Visit 7); last visit is defined as the visit where the endpoint is assessed.
For analyses of Study Period II, baseline is defined as the last non-missing observation at or before the randomization visit (Visit 2) unless otherwise specified. Endpoint for Study Period II is defined as the last non-missing observation obtained from Visit 3 through Visit 7. Baseline for Study Period III is defined as the observation from Visit 7. Endpoint for Study Period III is defined as the last nonmissing observation obtained from Visit 8 through Visit 20. Baseline for Study Period IV is defined as the last nonmissing observation obtained in Study Period II or III prior to entering Study Period IV (Visit 4 through Visit 20). Endpoint for Study Period IV is defined as Visit 21. |
|
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.6.13.1 | Other scope of the trial description |
| Bioanalytical, Health outcome |
|
| 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) | 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 | No |
| 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 | 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 | 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
|
End of study (trial) is defined as the date of the last visit or last scheduled
procedure at the last site shown in the Study Schedule for the last active subject
in the study. |
|
| 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 | 2 |
| 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 | 3 |
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