A study to evaluate the safety and efficacy of JNJ 42847922 along with your antidepressant in adult patients with Major Depressive Disorder whose antidepressant medication has not satisfactorily treated their symptoms

Phase 1

• Conditions: Major Depressive Disorder (MDD); MedDRA version: 20.0 Level: LLT Classification code 10025453 Term: Major depressive disorder NOS System Organ Class: 100000004873; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-005282-22-DE
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-04
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 280

Inclusion Criteria

1. Men or WONCBP, aged 18 to 70 years (inclusive). Note: Subjects should be at least 18 years of age or older as per the legal age of consent in the jurisdiction in which the study is taking place.
A WONCBP is defined as:
o Postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH)
level (>40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.
o Permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
If reproductive status is questionable, additional evaluation should be considered.
2. Meet DSM-5 diagnostic criteria for MDD, without psychotic features (DSM-5 296.22, 296.23, 296.32, or 296.33), based upon clinical assessment and confirmed by the SCID-CT. In addition, their major depressive episode must be deemed valid” using the SSQ interview administered by remote, independent raters. The length of the current depressive episode must be =18 months.
3. Have had an inadequate response to at least 1 but no more than 3 antidepressants (see the inclusion criterion below), administered at an adequate dose and duration in the current episode of depression, as measured by the MGH-ATRQ. An inadequate response is defined as <50% reduction in depressive symptom severity, as assessed by the MGH-ATRQ. An adequate trial is defined as an antidepressant treatment for at least 4 weeks at or above the minimum therapeutic dose specified in the MGH-ATRQ, for any particular antidepressant. The inadequate response must include the subject’s current antidepressant treatment.
4.Is receiving monotherapy treatment for depressive symptoms with one of the following SSRI/SNRI antidepressants, in any formulation: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable dose (at or above the minimum therapeutic dose level) for at least 4 weeks, and for no greater than 12 months, at screening. Modification of an effective preexisting therapy should not be made for the explicit purpose of entering a subject into the study.
Note: Dose and duration of treatment should be verified by the investigator using the medical or pharmacy records. The investigator will use this information to complete the MGH-ATRQ, which will then be corroborated by the independent rater.
5. Have a MADRS total score =25 (performed by independent, centralized remote raters) at screening and must not demonstrate a clinically significant improvement (ie, an improvement of >20% on their MADRS total score) from the screening to baseline visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Has a history of, or current signs and symptoms of, severe renal insufficiency (creatinine clearance <30 mL/min); moderate to severe hepatic insufficiency (Child-Pugh Score 7-9), significant or unstable cardiovascular, respiratory, gastrointestinal, neurologic (including narcolepsy), hematologic, rheumatologic, immunologic or endocrine disorders (including uncontrolled hypo- or hyperthyroidism or diabetes, or insulin-dependent diabetes mellitus). Subjects with non-insulin dependent diabetes mellitus who are well-controlled (hemoglobin A1C [HbA1C] =7.5% and fasting glucose <126 mg/dL at screening) may be eligible to participate if otherwise medically healthy, and if on a stable regimen of glucose-lowering medications for at least 2 months prior to screening.
2. Has current signs/symptoms of hypothyroidism or hyperthyroidism (Subjects with known hypothyroidism who have been on stable treatment for at least 3 months prior to screening are required to have thyroid-stimulating hormone [TSH] and free thyroxine [FT4] obtained. Any subject with an elevated TSH should also have FT4 measured. In any case where the TSH value is out of range, but FT4 is normal, the findings should be discussed directly with the medical monitor before the subject is enrolled. If the FT4 value is out of range, the subject is not eligible. Subjects taking thyroid supplementation for antidepressant purposes are not allowed in the study).
3. Has signs and symptoms of Cushing’s Disease, Addison’s Disease, primary amenorrhea, or other evidence of significant medical disorders of the HPA axis.
4. Has a current or recent history of serious suicidal ideation within the past 6 months, corresponding to a positive response on item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) for ideation on the 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 within the past 6 months, should be carefully screened for current suicidal ideation and only subjects with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be included at the discretion of the investigator.
5. Has a history of lack of response to 3 or more adequate antidepressant treatments, as indicated by no or minimal (=25% improvement in symptoms) when treated with an antidepressant of adequate dose (per MGH-ATRQ) and duration (at least 4 weeks).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified