E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder with Anxiety Symptoms |
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E.1.1.1 | Medical condition in easily understood language |
Depression is a mental disorder characterized by low mood and/or the loss of interest or pleasure in nearly all activities |
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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 | 10025454 |
E.1.2 | Term | Major depressive disorder, recurrent episode |
E.1.2 | System Organ Class | 100000004873 |
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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 evaluate the efficacy, as assessed by the change from baseline on a 6-item subscale derived from the Hamilton Anxiety Scale (HAM-A6), and overall safety and tolerability of treatment with adjunctive JNJ-40411813 compared to placebo in patients with MDD with anxiety symptoms being treated with an antidepressant. |
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E.2.2 | Secondary objectives of the trial |
•Assess impact of adjunctive JNJ-40411813 compared to placebo on anxiety symptoms, assessed by change from baseline on the 14-item Structured Interview Guide for Hamilton Anxiety Scale (total score & response), 17-item Hamilton Depression Rating Scale (HDRS17) anxiety/somatization factor total score, and Inventory of Depressive Symptomatology (IDS-C30) anxiety subscale score; and on change in percentage of subjects meeting criteria for anxious depression.
•Assess impact of adjunctive JNJ-40411813 compared to placebo on depressive symptoms assessed by change from baseline in HDRS17 (total score, response, & remission), HAM-D6 total score, and IDS-C30 total score.
•Assess impact of adjunctive JNJ-40411813 compared to placebo on other clinician & patient-rated assessments of mood, anxiety, sleep, and work productivity.
•Assess for withdrawal symptoms following cessation of JNJ-40411813 with the Physician Withdrawal Checklist. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Be a man or woman 18 to 64 years of age, inclusive.
• Subjects must have a primary DSM-IV diagnosis of MDD. Subjects with a diagnosis of comorbid Generalized Anxiety Disorder (GAD), Social Anxiety Disorder, or Panic Disorder may be included, if the investigator considers MDD to be the primary diagnosis (confirmed by independent rater at screening)
• A HDRS17 total score ≥ 18, by independent rater at screening and by the site rater on Day 1.
• A HDRS17 anxiety/somatization factor score ≥ 7, by the independent rater at screening and by the site rater on Day 1.
o HDRS17 anxiety/somatization factor items: Anxiety-psychic, Anxiety-somatic, Loss of Appetite (Somatic Symptoms – Gastrointestinal), Somatic Symptoms – General, Hypochondriasis, Loss of Insight
• Is receiving an antidepressant at an optimal dose and for at least 4 weeks, and no greater than 12 weeks, at Screening.
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E.4 | Principal exclusion criteria |
• Has any other current Axis I psychiatric condition, including, but not limited to, MDD with psychotic features (lifetime), bipolar disorder (including lifetime diagnosis), obsessive-compulsive disorder, post-traumatic stress disorder, borderline personality disorder, eating disorder (eg, bulimia, anorexia nervosa), or schizophrenia. As noted, subjects with a diagnosis of comorbid GAD, Social Anxiety Disorder, or Panic Disorder may be included.
• Has a length of current major depressive episode (MDE) > 6 months
• Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 (active suicidal ideation with some intent to act, without specific plan) or 5 (active suicidal ideation with specific plan and intent) for ideation on the Columbia Suicide Severity Rating Scale (C-SSRS), or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening or Day 1.
Subjects with a prior suicide attempt of any sort, or prior serious suicidal ideation/plan > 6 months ago, should be carefully screened for current suicidal ideation and only included at the discretion of the investigator.
• Not including the inadequate response to the current antidepressant, has no more than 1 failed antidepressant treatment of adequate dose and duration in the current major depressive episode.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this study will be the improvement in core anxiety symptoms, as measured by the change from baseline in the HAM-A6 score from baseline to the 4-week endpoint for the combined periods in the double-blind treatment phase (see Statistical Methods, Efficacy Analyses). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The change from baseline to the 4-week endpoint for the combined periods in the double-blind treatment phase for: HDRS17 total score, HDRS17 anxiety-somatization factor total score, HAM-D6 total score, IDS-C30 total score, IDS-C30 anxiety subscale score, Work Limitations Questionnaire (WLQ), Perceived Stress Scale (PSS), Profile of Mood States-Brief Form (POMS-BF), Medical Outcomes Study- Sleep Scale Acute - Revised (MOS Sleep-R), SIGH-A total score, and the Clinical Global Impression – Improvement (CGI-I) value
• The distribution of those meeting criteria for anxious depression, defined as the number and percentage of subjects with a HDRS17 anxiety/somatization factor score ≥ 7.
• The distribution of responders (based on two definitions) and remitters on depressive symptoms as assessed on the HDRS17 at the 4-week endpoint for the combined periods in the double-blind treatment phase, defined as the number and percentage of subjects that are responders (either ≥ 50% or ≥ 30% improvement on HDRS17 total score from baseline) and that are in remission (HDRS17 total score ≤ 7).
• The distribution of responders as assessed on the SIGH-A at the 4-week endpoint for the combined periods in the double-blind treatment phase, defined as the number and percentage of subjects that are responders ( ≥ 50% improvement on SIGH-A total score from baseline).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 12 |
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 |
Bulgaria |
Hungary |
Romania |
Russian Federation |
Ukraine |
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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
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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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |