| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major depressive disorder (MDD) |
|
| E.1.1.1 | Medical condition in easily understood language |
Mental disorder causing a pervasive depressed mood.
|
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025453 |
| E.1.2 | Term | Major depressive disorder NOS |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| 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 of this study is to assess whether LY2216684 (12 mg to 18 mg flexible dose once daily [QD]) is superior to placebo QD in the adjunctive treatment of patients with major depressive disorder [MDD; as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision® (DSM-IV-TR)] who were identified as partial responders to an adequate course of treatment with a selective serotonin reuptake inhibitor (SSRI), during an 11-week, double-blind, acute adjunctive treatment period.
Superiority is defined as a statistically greater reduction in depressive symptoms from baseline to the last visit in the adjunctive treatment phase, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score. |
|
| E.2.2 | Secondary objectives of the trial |
- to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo in improving global functioning
- to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo in achieving remission at the last visit in the adjunctive treatment phase.
- to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo in achieving remission at least at the patient's last 2 consecutive visits in the adjunctive treatment period.
- to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo as an adjunctive treatment for patients with MDD who are partial responders to their SSRI treatment in improving anxiety symptoms |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] meet criteria for primary MDD, as defined by DSM-IV-TR criteria, as
determined by clinical assessment and confirmed by the MINI at Visit 1
[2] are adult male or female outpatients at least 18 years of age or older at the time of informed consent, who provide informed consent by signing the appropriate ICFs. Patients must be competent and able to give their own informed consent.
[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 study entry 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 and for 1 month following the last dose of investigational product. Men participating agree to use a reliable method of birth control during the study, and for 1 month following the last dose of the investigational drug.
[4] are being treated with one of the following SSRIs that have been approved for MDD treatment within the participating country: escitalopram, citalopram, sertraline, fluoxetine, paroxetine, or fluvoxamine; and have been treated with their SSRI at least 6 weeks prior to Visit 2 with at least the last 4 consecutive weeks at a stable optimized dose prior to Visit 2. The SSRI should be prescribed, including dose, in a manner consistent with labeling guidelines within the participating country.
[5] meet criteria for partial response at Visit 1 and Visit 2, as defined by
investigator’s opinion that the patient has experienced a minimally clinically meaningful improvement with the SSRI treatment.
[6] have a GRID-HAMD17 total score16 at Visit 1.
[7] have 75% improvement on the current SSRI at Visit 1, determined by the
MGH-ATRQ-Modified Version
[8] have an education level and a degree of understanding such that the patient
can communicate with the site study personnel
[9] are 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 |
[10] are investigator site personnel directly affiliated with this study and/or their
immediate families. Immediate family is defined as a spouse, parent, child, or
sibling, whether biological or legally adopted.
[11] are Lilly employees
[12] are currently enrolled in, or discontinued within the last 30 days from, a
clinical study involving an investigational drug or device or off-label use of a
drug or device (other than the investigational product used in this study), or
concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study
[13] have previously completed or withdrawn from this study or any other study
investigating LY2216684
[14] have had or currently have any additional ongoing DSM-IV-TR Axis I
condition other than MDD that was considered the primary diagnosis within
1 year of Visit 1
[15] have had any anxiety disorder that was considered a primary diagnosis within
the past year (including panic disorder, obsessive-compulsive disorder [OCD],
posttraumatic stress disorder [PTSD], generalized anxiety disorder [GAD],
and social phobia, but excluding specific phobias)
[16] have a current or previous diagnosis of bipolar disorder, schizophrenia, or
other psychotic disorder
[17] have a history of substance abuse within the past 1 year (drug categories defined by DSM-IV-TR), and/or substance dependence within the past 1 year, not including caffeine and nicotine
[18] have an Axis II disorder that, in the judgment of the investigator, would interfere with compliance with the study protocol
[19] patients meet criteria for treatment-resistant depression, defined as a lack of clinically meaningfull 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.
[20] have a lifetime history of vagal nerve stimulation (VNS) transcranial magnetic stimulation (TMS), or psychosurgery
[21] have received electroconvulsive therapy (ECT) in the past year
[22] are women who are pregnant or breast-feeding
[23] are judged, in the opinion of the investigator, to be at serious risk for harm to
self or others
[24] have a serious or unstable medical illness, including cardiovascular, hepatic,
respiratory, hematologic, endocrinologic, neurologic disease, renal disease, or
clinically significant laboratory or ECG abnormality. Clinically significant
lab or ECG abnormalities are those which, in the judgment of the investigator,
indicate a serious medical problem or require significant intervention.
[25] 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 history of
urinary hesitancy or retention
[26] have a history of severe allergies to more than 1 class of medication or
multiple adverse drug reactions
[27] have a history of any seizure disorder (other than febrile seizures)
[28] have received treatment with a monoamine oxidase inhibitor (MAOI) within
14 days prior to Visit 1 or have a potential need to use an MAOI within 3 days
after discontinuation from the study
[29] require psychotropic medication other than sedative/hypnotic medication, as specified in the protocol
[30] are taking or have received treatment with any excluded medications within
7 days prior to Visit 2
[31] in the judgement of the investigator, the patient is not considered to be euthyroid. If the patient has a TSH level outside the laboratory-established reference range, the investigator may test for T3 and T4 to determine if the patient is clinically euthyroid. Patients who were previously diagnosed with hyperthyroidism or hypothyroidism and are receiving treatment must have been treated with a stable dose of thyroid supplement for at least the past 3 months.
[32] have initiated or discontinued hormone therapy within the previous 3 months
prior to enrollment
[33] have initiated psychotherapy, or other nondrug therapies (such as acupuncture
or hypnosis) within 12 weeks prior to enrollment or at any time during the
study. No change in intensity of psychotherapy within the last 6 weeks prior
to enrollment or at any time during the study
[34] have a positive urine drug screen (UDS) for any substances of abuse at Visit
1. Note: A retest may be performed if the UDS is positive for any prescribed
substance or if, in the judgment of the investigator, there is an acceptable
explanation for the positive result. The results of the retest must be negative
at or prior to Visit 2. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to the last visit in the adjunctive treatment phase, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weekly for 11 weeks starting at the enrolment visit (Day 0) for 11 weeks.
|
|
| E.5.2 | Secondary end point(s) |
-to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo as an adjunctive
treatment for patients with MDD who are partial responders to their SSRI treatment in
improving global functioning, as measured by change from baseline to the last visit in the
adjunctive treatment phase in the Sheehan Disability Scale (SDS) Global Functional
Impairment score
-to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo as an adjunctive
treatment for patients with MDD who are partial responders to their SSRI treatment in
achieving remission at the last visit in the adjunctive treatment phase. Remission is
defined as MADRS total score ≤10
-to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo as an adjunctive
treatment for patients with MDD who are partial responders to their SSRI treatment in
achieving remission at least at the patient’s last 2 consecutive visits in the adjunctive
treatment period
-to assess whether LY2216684 12 mg to 18 mg QD is superior to placebo as an adjunctive
treatment for patients with MDD who are partial responders to their SSRI treatment in
improving anxiety symptoms, as measured by change from baseline to last visit in the adjunctive treatment phase in the Hospital Anxiety and Depression Scale (HADS)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints are measured from Day 0 till Week 11. Refer to Protocol Attachment 1 for details (Study Schedule)
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| 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 | No |
| 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 |
| Austria |
| Belgium |
| Germany |
| Sweden |
| United Kingdom |
| United States |
|
| 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
|
| End of study is the date of the last visit or last scheduled procedure shown in the Study Schedule for the last active patient in the study. |
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
