Quetiapine Sr as Adjunctive Treatment In Mixed States of Bipolar Disorder

• Sponsor: The University of Texas Health Science Center at San Antonio (Other)
• Overall Status: Completed
• CT.gov ID: NCT01195363
• Collaborator: AstraZeneca (Industry)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

To assess the acute and long-term bimodal efficacy of QTP, as an adjunct to ongoing treatment with lithium (Li) or divalproex (DIV) or lamotrigine (LAM) or any combination of the three thereof, in a group of patients with an index episode of a mixed state in BD.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: quetiapine SR; Drug: quetiapine sr placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo Controlled Study Of Quetiapine SR (QTP) As Adjunctive Treatment In Mixed States (MS) Of Bipolar Disorder
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: quetiapine SR quetiapine SR, 200-600mg, po, qd	Drug: quetiapine SR; quetiapine SR, dose range 200-600mg, each night QHS for 6mos; Other Names: Seroquel SR
Placebo Comparator: quetiapine sr Placebo quetiapine SR placebo, 200-600mg, po qd	Drug: quetiapine sr placebo; quetiapine sr placebo, dose range 200-600mg, each night QHS for 6mos

Outcome Measures

Primary Outcome Measures

1. Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores. [Baseline visit to week 24]

   The primary outcome measure was assessed by 50% reduction in: 1. depression scores on the Montgomery Asberg Depression Rating Scale (MADRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms 2. mania scores on the Young Mania Rating Scale (YMRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female;

• Age 18 years and older

• Patients on:

• Li at a stable dose for 4 weeks or longer, and a serum level at screening of 0.5 mEq/l OR

• DIV dose for 4 weeks or longer, and a serum level at screening of 45 g/ml OR

• LAM (dosage/day ≥100mg) at a stable dose for 4 weeks or longer OR

• Any combination 3a, 3b, or 3c

• Patients meeting DSM-IV TR diagnosis of bipolar disorder, I or II, as assessed using the MINI, (Sheehan et al., 1998) PLUS any ONE of criteria 5 or 6 or 7

• Patients meeting DSM-IV TR diagnostic criteria for a mixed manic episode with Young Mania Rating Scale (YMRS) score>/=14 and Montgomery Asberg Depression Rating Scale (MADRS) score>/=14

• Patients meeting the criteria for a manic/hypomanic episode for at least 2 days with the simultaneous presence of Young Mania Rating Scale (YMRS) score>/=14 PLUS Montgomery Asberg Depression Rating Scale (MADRS) score>/=14 ;

• Patients meeting DSM-IV TR diagnostic criteria for a major depressive episode with the simultaneous presence of MADRS score>/=14 PLUS meeting the criteria for a manic/hypomanic episode for at least 2 days with the simultaneous presence of Young Mania Rating Scale (YMRS) score>/=14

Exclusion Criteria:

• Patients with a current Axis I diagnosis of schizophrenia, schizophreniform disorder, schizotypal disorder, bipolar disorder with psychotic subtype, drug induced mania or AIDS induced mania

• Women with a positive pregnancy test or who are lactating

• Women of child-bearing potential who are not practicing a clinically accepted method of contraception

• Patients with general medical conditions that contraindicate psychoactive medications or uncontrolled medical disorder or central nervous system diseases.

• Patients whose clinical status requires inpatient or day hospital treatment

• History of severe side effects associated with therapeutic doses of Li, DIV, LAM

• Alcohol or drug dependent at time of enrollment

• Suicidal at time of enrollment.

• Current or previous exposure to QTP

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• The University of Texas Health Science Center at San Antonio
• AstraZeneca

Investigators

• Principal Investigator: Charles Bowden, MD, University of Texas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Charles L. Bowden, MD, The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT01195363
• Other Study ID Numbers: HSC20070253H
• First Posted: Sep 6, 2010
• Last Update Posted: Mar 23, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Charles L. Bowden, MD, The University of Texas Health Science Center at San Antonio: bipolar disorder, mania, depression
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	Participants were recruited in our University, Center for Healthcare Services, and by televison ads between Oct 2007 and January 2011.
Pre-assignment Detail	Patients screened over a 7 day period.

Arm/Group Title	Quetiapine SR, 200-600mg , po, QD	Quetiapine sr Placebo 200-600mg, po, qd
Arm/Group Description	mood stabilizer plus active quetiapine SR	mood stabilizer plus quetiapine SR placebo
Period Title: Overall Study
STARTED	15	13
COMPLETED	4	4
NOT COMPLETED	11	9

Baseline Characteristics

Arm/Group Title	Active Quetiapine SR	Quetiapine SR Placebo	Total
Arm/Group Description	mood stabilizer plus active quetiapine sr	mood stabilizer plus quetiapine SR placebo	Total of all reporting groups
Overall Participants	15	13	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	13 100%	28 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.5 (10.1)	32.1 (9.8)	34 (9.9)
Sex: Female, Male (Count of Participants)
Female	8 53.3%	11 84.6%	19 67.9%
Male	7 46.7%	2 15.4%	9 32.1%
Region of Enrollment (participants) [Number]
United States	15 100%	13 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Whose Mood Improved According to MADRS and YMRS Scale Scores.
Description	The primary outcome measure was assessed by 50% reduction in: 1. depression scores on the Montgomery Asberg Depression Rating Scale (MADRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms 2. mania scores on the Young Mania Rating Scale (YMRS), which ranges from 0 indicating no symptoms to 60 indicating most symptoms.
Time Frame	Baseline visit to week 24

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	Active Quetiapine S.R., 200-600mg, po, qd	Placebo Quetiapine S.R. 200-600mg, po, qd
Arm/Group Description	Atypical antipsychotic quetiapine S.R. plus mood stabilizer	mood stabilizer plus quetiapine S.R. placebo
Measure Participants	15	13
MADRS	4 26.7%	4 30.8%
YMRS	4 26.7%	4 30.8%

Adverse Events

Time Frame	10/30/2007 - 6/1/2011, 2 yrs 8 mos.
Arm/Group Title	Mood Stabilizer Plus Quetiapine SR		Mood Stabilizer Plus Quetiapine sr Placebo
Arm/Group Description	mood stabilizer plus active quetiapine SR		mood stabilizer plus quetiapine SR placebo
All Cause Mortality
	Mood Stabilizer Plus Quetiapine SR		Mood Stabilizer Plus Quetiapine sr Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mood Stabilizer Plus Quetiapine SR		Mood Stabilizer Plus Quetiapine sr Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Mood Stabilizer Plus Quetiapine SR		Mood Stabilizer Plus Quetiapine sr Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/15 (66.7%)		7/13 (53.8%)
Gastrointestinal disorders
nausea	2/15 (13.3%)	2	0/13 (0%)	0
General disorders
dry mouth	4/15 (26.7%)	4	2/13 (15.4%)	2
joint pain	2/15 (13.3%)	2	0/13 (0%)	0
headache	1/15 (6.7%)	1	2/13 (15.4%)	2
Investigations
drowsiness/sedation	7/15 (46.7%)	7	3/13 (23.1%)	3
interrupted sleep	2/15 (13.3%)	2	0/13 (0%)	0
Metabolism and nutrition disorders
increased appetite	1/15 (6.7%)	1	2/13 (15.4%)	2
Musculoskeletal and connective tissue disorders
muscle weakness	2/15 (13.3%)	2	0/13 (0%)	0

Limitations/Caveats

Overall limitations were screen failures and lost to follow-ups which led to not reaching recruitment goals.

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.