Geodon: A 12-Week, Placebo Controlled Trial of Ziprasidone as Monotherapy for Major Depressive Disorder

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00555997
• Collaborator: Cambridge Health Alliance (Other), University of Connecticut (Other), Vanderbilt University (Other), Psychiatric Medicine Associates, L.L.C. (Other), Cedars-Sinai Medical Center (Other)
• Enrollment: 120
• Locations: 7
• Arms: 3
• Duration (Months): 27
• Patients Per Site: 17.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is a study on the effectiveness, tolerability and safety of oral ziprasidone as monotherapy in patients with major depressive disorder (MDD). Outpatients suffering from MDD will be treated with either ziprasidone or placebo for 12 weeks.

Hypothesis: There will be a statistically significant difference in the magnitude of response, as measured by a decrease in baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores, between the two treatment groups; the reduction in HAM-D-17 scores will be greater in the ziprasidone monotherapy group than in the placebo group.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Ziprasidone; Drug: Ziprasidone; Drug: Placebo	Phase 2

Detailed Description

Exploratory hypothesis 1: There will be a statistically significant difference in the percentage of responders in the two treatment groups; response rates will be significantly higher for the ziprasidone monotherapy compared to the placebo group.

Exploratory hypothesis 2: The change in 6-VAS-D scores during the trial will be highly correlated to the change in HAM-D-17 and QIDS-SR during the trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Patients in group 1 will receive Ziprasidone for the full 12 weeks of the study.	Drug: Ziprasidone; 20mg-80mg a day. Dose increases of 20mg per day may occur at three study visits as directed by clinician. Maximum; 80mg per day per patient.; Other Names: Geodon
Active Comparator: 2 Patients in Group 2 will receive placebo for the first 6 weeks of the study, then will receive Ziprasidone for the last 6 weeks.	Drug: Ziprasidone; 20mg-80mg a day. Dose increases of 20mg per day may occur at three study visits as directed by clinician. Maximum; 80mg per day per patient.; Other Names: Geodon
Placebo Comparator: 3 Patients in Group 3 will receive placebo for the full 12 weeks of the study.	Drug: Placebo; 0mg Placebo per day. "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale (HAM-D-17) Scores [6 weeks]

   Higher numbers represent more symptoms of a major depressive episode. Minimum is 0. Maximum is 52.

Secondary Outcome Measures

1. Responder/Non-responder [6 weeks]

   A responder during phase 1 or phase 2 is someone who demonstrated a 50% or greater decrease in HAMD-17 scores during phase 1 or phase 2 (corresponding).

2. Change in 6-VAS-D Scores During Each Phase. [6 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 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 (MINI; Sheehan et al, 1998).

4. Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR- Trivedi et al,

1. 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 screen visit. If interested in discontinuing their current medication, potential participants must discuss this possibility with the prescribing physician. Study doctors will not implement any form of treatment washout.

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 (see table 1 for details).

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 (i.e. QTc>450msec), 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	University of Connecticut Health Center	Farmington	Connecticut	United States	06030-6415
3	Comprehensive Psychiatric Care	Norwich	Connecticut	United States	06360
4	Psychiatric Medicine Associates, L.L.C.	Chicago	Illinois	United States	60612
5	Massachusetts General Hosptial	Boston	Massachusetts	United States	02114
6	Cambridge Health Alliance	Cambridge	Massachusetts	United States	02139
7	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212

Sponsors and Collaborators

• Massachusetts General Hospital
• Cambridge Health Alliance
• University of Connecticut
• Vanderbilt University
• Psychiatric Medicine Associates, L.L.C.
• Cedars-Sinai Medical Center

Investigators

• Principal Investigator: George I Papakostas, M.D., Massachusetts General Hospital
• Principal Investigator: John M Zajecka, M.D., Psychiatric Medicine Associates, L.L.C.
• Principal Investigator: Richard C Shelton, M.D., Vanderbilt University Medical Center
• Principal Investigator: Andrew Winokur, M.D., UConn Health
• Principal Investigator: Gustavo Kinrys, M.D., Cambridge Health Alliance
• Principal Investigator: Waguih IsHak, M.D., Cedar's Sinai
• Principal Investigator: Mahmoud S Okasha, MD, Comprehensive Psychiatric Care, Norwich CT

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: George I. Papakostas, Director of Treatment-Resistant Studies, Depression Clinical and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00555997
• Other Study ID Numbers: 2007-P-000623; NCT00657592
• First Posted: Nov 9, 2007
• Last Update Posted: Jul 3, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by George I. Papakostas, Director of Treatment-Resistant Studies, Depression Clinical and Research Program, Massachusetts General Hospital: Major Depressive Disorder; Major Depression; Depression; Geodon; Ziprasidone
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Ziprasidone

Study Results

Participant Flow

Arm/Group Title	Phase 1 Ziprasidone	Phase 1 Placebo	Phase 2 Ziprasidone	Phase 2 Placebo
Arm/Group Description	Subjects taking ziprasidone in the first phase.	Subjects taking placebo in the first phase.	Subjects taking ziprasidone in the second phase.	Patients who received placebo in phase 2.
Period Title: Phase 1 SPCD
STARTED	29	91	0	0
COMPLETED	17	76	0	0
NOT COMPLETED	12	15	0	0
Period Title: Phase 1 SPCD
STARTED	0	0	38	25
COMPLETED	0	0	31	22
NOT COMPLETED	0	0	7	3

Baseline Characteristics

Arm/Group Title	Placebo/Ziprasidone	Placebo	Ziprasidone	Total
Arm/Group Description	Received placebo in first phase and ziprasidone in second phase	Subjects received placebo throughout study	Subjects received ziprasidone throughout study	Total of all reporting groups
Overall Participants	47	44	29	120
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	47 100%	42 95.5%	29 100%	118 98.3%
>=65 years	0 0%	2 4.5%	0 0%	2 1.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (11.1)	44.6 (11.0)	41.5 (10.6)	43.7 (11.0)
Sex: Female, Male (Count of Participants)
Female	18 38.3%	22 50%	13 44.8%	53 44.2%
Male	29 61.7%	22 50%	16 55.2%	67 55.8%
Region of Enrollment (participants) [Number]
United States	47 100%	44 100%	29 100%	120 100%

Outcome Measures

1. Primary Outcome

Title	Hamilton Depression Rating Scale (HAM-D-17) Scores
Description	Higher numbers represent more symptoms of a major depressive episode. Minimum is 0. Maximum is 52.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone Phase I	Placebo Phase I	Ziprasidone Phase II	Placebo Phase II
Arm/Group Description	Results from phase I for those taking ziprasidone during that phase	Results from phase I for those taking placebo during that phase	Results from phase II for those taking ziprasidone during that phase	Results from phase II for those taking placebo during that phase
Measure Participants	29	91	21	25
Mean phase baseline score	20.1 (5.5)	19.9 (4.8)	14.7 (3.9)	15.6 (5.9)
Mean phase score reduction	-8.8 (7.3)	-7.1 (7.0)	-2.1 (5.2)	-4.3 (6.0)

2. Secondary Outcome

Title	Responder/Non-responder
Description	A responder during phase 1 or phase 2 is someone who demonstrated a 50% or greater decrease in HAMD-17 scores during phase 1 or phase 2 (corresponding).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ziprasidone Phase I	Placebo Phase I	Ziprasidone Phase II	Placebo Phase II
Arm/Group Description	Results from phase I for those taking ziprasidone during that phase	Results from phase I for those taking placebo during that phase	Results from phase II for those taking ziprasidone during that phase	Results from phase II for those taking placebo during that phase
Measure Participants	29	91	21	25
Number [percentage of patients]	44.8	31.8	23.8	28.0

3. Secondary Outcome

Title	Change in 6-VAS-D Scores During Each Phase.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Forms not analyzable due to insufficient standardization across sites.

Arm/Group Title	Phase 1 Ziprasidone	Phase 1 Placebo	Phase 2 Ziprasidone	Phase 2 Placebo
Arm/Group Description	Subjects taking ziprasidone in the first phase.	Subjects taking placebo in the first phase.	Subjects taking ziprasidone in the second phase.	Patients who received placebo in phase 2.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	1 year, 4 months
Arm/Group Title	Ziprasidone		Placebo
Arm/Group Description	Adverse events experienced by subjects while taking ziprasidone		Adverse events experienced when taking placebo
All Cause Mortality
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		1/125 (0.8%)
Psychiatric disorders
Hospitalization due to suicidal ideation	0/80 (0%)	0	1/125 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Ziprasidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/125 (24.8%)		22/80 (27.5%)
Gastrointestinal disorders
Dry mouth	6/125 (4.8%)		6/80 (7.5%)
Constipation	3/125 (2.4%)		3/80 (3.8%)
Increased appetite	3/125 (2.4%)		0/80 (0%)
Nausea	1/125 (0.8%)		2/80 (2.5%)
Weight gain	0/125 (0%)		1/80 (1.3%)
General disorders
Sexual dysfunction	1/125 (0.8%)		2/80 (2.5%)
Nervous system disorders
Headache	3/125 (2.4%)		2/80 (2.5%)
Dizziness	2/125 (1.6%)		2/80 (2.5%)
Blurry/Double Vision	2/125 (1.6%)		2/80 (2.5%)
Psychiatric disorders
Sedation/Fatigue	13/125 (10.4%)		3/80 (3.8%)
Insomnia	2/125 (1.6%)		3/80 (3.8%)
Akathisia/Agitation	1/125 (0.8%)		1/80 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.