Vortioxetine in Patients With Major Depressive Disorder and Coronary Artery Disease

• Status: Withdrawn
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a preliminary, open-label, clinical trial designed to assess the efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients with coronary artery disease. In addition, the study will assess the effects of vortioxetine on heart rate variability in these patients.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thomas Jefferson University
• Collaborator: Takeda
• Treatments: Vortioxetine

Criteria

Inclusion Criteria:

1. DSM-5 diagnosis of a major depressive disorder based on clinical evaluation by the study psychiatrist

2. At least moderate severity of depression as indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 22 or greater

3. History of coronary artery disease as defined by:

• History of coronary stenosis in one or more vessels that is greater ≥ 70% by coronary angiography or CT angiogram, OR

• History of abnormal stress test (at least medium-sized, moderate, reversible defect), OR

• History of documented myocardial infarction including ST elevation myocardial infarction or non-ST elevation myocardial infarction (with elevated troponins), OR

4. Evidence of adequate treatment of the coronary artery disease as defined by at least one of the following that was done at least six months prior to the Screening visit, AND was followed by the patient being clinically stable in the opinion of a cardiologist who has evaluated the case:

• Coronary artery bypass grafting (CABG)

• Percutaneous coronary intervention (PCI)/ stenting

• Adequate management with optimal medical treatment (such as one or more of the following medications: aspirin, beta blockers, a statin (e.g., atorvastatin), and either an ACE inhibitor or an angiotensin-receptor blocker.)

Key Exclusion Criteria:

Psychiatric Exclusion Criteria:

1. Patients who in the past have failed to respond to a trial of vortioxetine at the minimum recommended dose (10 mg/day) or greater taken for at least six weeks, or had unacceptable adverse effects while taking vortioxetine.

2. Patients must not have failed treatment with more than one antidepressant (taken at an adequate dose and for at least six weeks) in the current episode of major depressive disorder (i.e., did not have > 50% reduction in severity of depression based on patient history)

3. Patients with a current primary DSM-5 diagnosis of:

i) Delirium, dementia, amnestic, or other cognitive disorder; ii) Eating Disorder (including Anorexia Nervosa or Bulimia); iii) Obsessive Compulsive Disorder; iv) Panic Disorder; v) Post-Traumatic Stress Disorder (PTSD);

4. Current or past (lifetime) DSM-5 diagnosis of:

i) Bipolar I or II disorder; ii) Hypomanic episode iii) Substance-induced manic or hypomanic episode iii) Schizophrenia or other psychotic disorder

Cardiovascular Exclusion Criteria:

1. Patients who have had a myocardial infarction within 30 days of the screening visit

2. Any cardiovascular condition that is unstable or decompensated

3. In the opinion of the Investigators, the patient is at significant risk of cardiovascular adverse events

4. Coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)/ stenting within three months of the screening visit

5. Admission to a hospital for any cardiac condition within three months of the screening visit

6. Decompensated heart failure within 6 months of the screening visit

7. QTc prolongation (screening ECG with QTc ≥ 450 msec for men or QTc ≥ 470 msec for women) using QTc Fridericia correction

8. Second-degree (if Mobitz II) or third-degree atrioventricular block

9. Heart rate on ECG of ≤ 50 bpm or ≥ 120 bpm or any heart rate that is clinically symptomatic

10. Premature Ventricular Contractions (PVCs) associated with clinical symptoms and/or any complex premature ventricular contractions (ie, PVCs that are frequent [> 30/hr] or ≥ 2 beats if multifocal, or show bigeminy, trigeminy, quadrigeminy, couplets, triplets [salvos], or the R on T phenomenon)

11. Atrial fibrillation or flutter

12. Supine (after patient has been supine for 5 minutes) systolic BP > 160 mm Hg or < 90 mm Hg or diastolic BP > 100 mm Hg or any systolic or diastolic BP that is symptomatic or clinically significant based on the opinion of the Principal Investigator

13. Patients who are receiving warfarin