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Treatment of Major Depressive Disorder (MDD) With Ziprasidone

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT00657592
First received: April 8, 2008
Last updated: March 26, 2012
Last verified: March 2012
  Purpose

This is a 12-week, double-blind, placebo-controlled study on the efficacy, tolerability and safety of oral ziprasidone as monotherapy in patients with (major depressive disorder) MDD. The study involves the enrollment of a total of 120 patients with MDD over the course of 12 months across two sites. Outpatients suffering from MDD will be treated with either ziprasidone or with placebo for 12 weeks using the sequential parallel comparison design.

In light of the challenge major depressive disorder (MDD) poses to clinicians and patients alike, identifying novel treatments is urgently needed to help further refine the standard of care. Judging by their molecular structure and function, the atypical neuroleptic agents offer possibilities as effective antidepressants. To date, several studies have been reported examining the use of atypical neuroleptic agents as adjunctive therapy (used along with an antidepressant) for MDD. These studies go so far as to suggest that atypical neuroleptic agents have potential for treating MDD. Until now, atypical neuroleptics have been strictly viewed as adjuncts, however, it is quite possible that some of the atypical neuroleptic agents may possess antidepressant properties when used as the lone therapy.

The atypical neuroleptic agent ziprasidone, in particular, is an excellent neuroleptic candidate for studying antipsychotic effects on MDD for two principal reasons: its structure makes it favorable for binding to neurotransmitters in the brain and it has fewer side-effects compared to the other drugs in its class. This study will be the first, double blind, placebo-controlled trial of ziprasidone as monotherapy for MDD. If safe and effective as an antidepressant, ziprasidone would represent an additional option for patients with MDD.

Potential subjects will be approached during a regularly scheduled clinic visit, upon referral from another physician, or in response to research advertisements. Interested individuals will have the opportunity to review the consent form with family, friends, and other physicians prior to making a final decision regarding study enrollment. Once the subject has given informed consent, the screening process for the study will commence.

Subjects will have a screening visit to determine eligibility. The screening visit consists of a medical evaluation, completion of psychological rating scales, physical/neurological exams, electrocardiogram, and the collection of blood and urine. After subjects pass screening, they will be randomized into one of 3 study groups. Subjects will receive either 12 weeks of ziprasidone, 12 weeks of placebo, or 6 weeks of placebo followed by 6 weeks of ziprasidone. Study participants will have a 5 in 8 chance of receiving ziprasidone at some point in the study.

Subjects will be closely monitored during the study via 2 phone calls weekly from the study coordinator. The overall safety of the study will also be well scrutinized. The investigators shall identify an independent physician safety monitor, who will be without any affiliation to this study. He/she will be provided all the information necessary to evaluate the study's safety parameters and whether or not they are effective preventative measures.

Various psychological assessments will be completed by research subjects at every study visit.

This research study is designed to test the safety and/or effectiveness of the investigational use of the drug Ziprasidone that has been approved by the U.S Food and Drug Administration (FDA). While the drug used in the study is FDA-approved for treating schizophrenia and Bipolar disorder I, it is not yet approved for alleviating solely the symptoms of depression.


Condition Intervention Phase
Depression
Drug: oral Ziprasidone
Drug: Placebo and Ziprasidone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Sequential Trial of Ziprasidone as Monotherapy for Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale [ Time Frame: 14 times for an average of 14 weeks ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: March 2008
Study Completion Date: December 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ziprasidone

The first research study group will receive oral Ziprasidone for Phases 1 and 2.

If you are randomized to group 1, during Phase 1, you will receive one pill (20 mg) of Ziprasidone to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks, if well tolerated, to a maximum of 4 pills (80 mg) taken twice daily.

During Phase 2, you will receive the same dose and frequency of Ziprasidone as administered during Phase 1. If you had not reached the maximum dose of 4 pills taken twice daily, your dosage will continue to be increased (if tolerated) each week by 1 pill taken twice daily until you reach the maximum dosage level.

Drug: oral Ziprasidone

Subjects in this group will receive one pill (20 mg) of Ziprasidone to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks, if well tolerated, to a maximum of 4 pills (80 mg) taken twice daily.

During Phase 2, you will receive the same dose and frequency of Ziprasidone as administered during Phase 1. If you had not reached the maximum dose of 4 pills taken twice daily, your dosage will continue to be increased (if tolerated) each week by 1 pill taken twice daily until you reach the maximum dosage level.

Experimental: Placebo/Ziprasidone

The second research study group will receive placebo for Phase 1 and Ziprasidone for Phase 2.

If you are randomized to group 2, during Phase 1, you will receive one pill (20 mg) of placebo to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks.

During Phase 2, you will receive one pill (20 mg) of Ziprasidone to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks, if well tolerated, to a maximum of 4 pills (80 mg) taken twice daily.

Drug: Placebo and Ziprasidone

If you are randomized to group 2, during Phase 1, you will receive one pill (20 mg) of placebo to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks.

During Phase 2, you will receive one pill (20 mg) of Ziprasidone to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks, if well tolerated, to a maximum of 4 pills (80 mg) taken twice daily.

Placebo Comparator: Placebo

The third research study group will receive placebo for Phases 1 and 2.

If you are randomized to group 3, during Phase 1, you will receive one pill (20 mg) of placebo to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks.

During Phase 2, you will continue to receive the same dose and frequency of placebo as administered during Phase 1. If you do not reach the maximum dose of 4 pills taken twice daily, your dosage will continue to be increased until you reach the maximum dosage level.

Drug: Placebo

If you are randomized to group 3, during Phase 1, you will receive one pill (20 mg) of placebo to be taken twice-a-day. This dose will be increased by 1 pill (20 mg) twice-a-day each week for 6 weeks.

During Phase 2, you will continue to receive the same dose and frequency of placebo as administered during Phase 1. If you do not reach the maximum dose of 4 pills taken twice daily, your dosage will continue to be increased until you reach the maximum dosage level.


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18-65.
  2. Written informed consent.
  3. MDD, current according to the fourth version of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) as diagnosed by the Mini International Neuropsychiatric Interview.
  4. Quick Inventory of Depressive Symptomatology - Self-Rated score of at least 10 at both screen and baseline visits.

Exclusion Criteria:

  1. Pregnant women.
  2. Women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or a partner with vasectomy).
  3. Treatment with antidepressants for 2 weeks prior to the study.
  4. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit, or patients who demonstrate a 25% or greater reduction in QIDS-SR scores, screening to baseline.
  5. Serious suicide or homicide risk, as assessed by the evaluating clinician or a score of 4 on the third item of the HAM-D.
  6. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
  7. Patients who meet criteria for alcohol or substance dependence, active within the last month.
  8. Any bipolar disorder (current or past).
  9. Any psychotic disorder (current or past).
  10. Psychotic features in the current episode or a history of psychotic features.
  11. History of a seizure disorder.
  12. Clinical or laboratory evidence of untreated hypothyroidism.
  13. Patients requiring excluded medications.
  14. Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
  15. Any investigational psychotropic drug within the last 3 months.
  16. Patients with significant cardiac conduction problems on screening electrocardiogram such as atrial fibrillation, atrial flutter, atrio-ventricular block, prolonged or abnormal QTc interval, or prolonged QRS interval.
  17. Patients who have suffered a myocardial infarction within the past 12 months, with uncompensated heart failure, or a history of QTc prolongation.
  18. Patients with abnormal serum potassium or magnesium levels upon screening.
  19. Patients currently taking other drugs that prolong the QTc including dofetilide, sotalol, quinidine, class Ia antiarrhythmics, class III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron methylate, probucol or tacrolimus.
  20. Patients who have failed to experience significant clinical improvement following 3 or more antidepressant trials of adequate duration (at least 6 weeks) and dose (minimal effective doses defined as: fluoxetine, paroxetine, citalopram 20mg; sertraline, fluvoxamine 50mg, escitalopram 10mg, paroxetine CR 25mg, venlafaxine 75mg, duloxetine 60mg, bupropion 150mg, 15mg of mirtazapine, trazodone or nefazodone 300mg).
  21. Patients with a QTc > 450msec at the Baseline visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00657592

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Pfizer
  More Information

No publications provided

Responsible Party: Dr. Waguih Ishak, M.D., Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT00657592     History of Changes
Other Study ID Numbers: 12027
Study First Received: April 8, 2008
Last Updated: March 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Cedars-Sinai Medical Center:
Depression
Los Angeles
Ziprasidone

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Ziprasidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 27, 2014