A Phase IV Study of the Safety and Efficacy of Aripiprazole in Combination With Lamotrigine in the Long-Term Maintenance Treatment of Patients With Bipolar I Disorder With A Recent Manic or Mixed Episode

This study has been completed.

Study NCT00277212 Information provided by Bristol-Myers Squibb

First Received on January 13, 2006. Last Updated on November 16, 2010 History of Changes

Results First Received: September 20, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Bipolar Disorder
Interventions:	Drug: Lamotrigine + Aripiprazole Drug: Lamotrigine + Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 1169 patients were enrolled in the study; 382 participants were considered baseline failures and did not enter Phase 1.

Reporting Groups

	Description
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole	Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo	Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole	Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.

Participant Flow for 2 periods

Period 1: Phase 1 - Single-Blind Treatment

	Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole	Phase 2 Double-Blind Treatment: Lamotrigine + Placebo	Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
STARTED	787	0	0
Phase 1 Safety Sample	787	0	0
Phase 1 Efficacy Sample	756	0	0
COMPLETED	352	0	0
NOT COMPLETED	435	0	0
Lack of Efficacy	61	0	0
Adverse Event	93	0	0
Withdrawal by Subject	96	0	0
Lost to Follow-up	87	0	0
Poor/Noncompliance	35	0	0
Pregnancy	6	0	0
Subject No Longer Met Study Criteria	44	0	0
Administrative Reason by Sponsor	1	0	0
Other Reasons	12	0	0

Period 2: Phase 2 - Double-Blind Treatment

	Phase 2 Double-Blind Treatment: Lamotrigine + Placebo	Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
STARTED	173	178 ^[1]
Phase 2 Safety Sample	165	176
Phase 2 Efficacy Sample	164	174
COMPLETED	53	65
NOT COMPLETED	120	113
Lack of Efficacy	54	39
Adverse Event	10	16
Withdrawal by Subject	17	16
Lost to Follow-up	18	18
Poor/Noncompliance	7	8
Pregnancy	2	2
Subject No Longer Meets Study Criteria	4	6
Administrative Reasons By Sponsor	1	3
Other reasons	7	5

[1]	1 participant did not want to continue in the study for personal reasons, and did not enter Phase 2.

Baseline Characteristics

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Reporting Groups

	Description
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole	Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks

Baseline Measures

	Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
Number of Participants [units: participants]	796
Age [units: years] Mean ± Standard Deviation	38.1 ± 12.0
Gender [units: participants]
Female	505
Male	291
Race/Ethnicity, Customized [units: participants]
White	693
Black/African American	88
Asian	10
American Indian/Alaska Native	2
Native Hawaiian/Other Pacific Islander	1
Other	2
Race/Ethnicity, Customized [units: participants]
Hispanic or Latino	93
Not Hispanic or Latino	703
Body Mass Index (BMI) [units: kg/m^2] Mean ± Standard Deviation	29.7 ± 7.6
Weight [units: kg] Mean ± Standard Deviation	84.7 ± 22.7
BMI Category [units: participants]
18.5 <= BMI <25	221
25 <= BMI <30	215
BMI <18.5	12
BMI >=30	321
Missing	27

Outcome Measures

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1. Primary:

Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) [ Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]

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2. Secondary:

Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 [ Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]

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3. Secondary:

Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) [ Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]

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4. Secondary:

Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) [ Time Frame: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ]

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5. Secondary:

Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation of Study Medication, Treatment-Emergent AEs and Treatment-Emergent Extrapyramidal Syndrome (EPS)-Related AEs [ Time Frame: Throughout Phase 2 (up to 52 weeks) ]

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6. Secondary:

Adjusted Mean Change From Baseline in Body Weight, Phase 2 [ Time Frame: Baseline, Week 52 ]

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7. Secondary:

Number of Participants Showing Clinically Relevant Weight Loss by Study Week [ Time Frame: Weeks 12, 24, 36, 52 ]

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8. Secondary:

Number of Participants Showing Clinically Relevant Weight Gain by Study Week [ Time Frame: Weeks 12, 24, 36, 52 ]

Show Outcome Measure 8

9. Secondary:

Adjusted Mean Change From Baseline in BMI by Study Week [ Time Frame: Baseline, Weeks 12, 24, 36, 52 ]

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10. Secondary:

Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment [ Time Frame: Throughout the study, up to Week 52 ]

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11. Secondary:

Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment [ Time Frame: Up to 52 Weeks ]

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12. Secondary:

Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) [ Time Frame: Throughout Phase 2 of the study, up to Week 52 ]

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13. Secondary:

Summary of Concomitant Medications, Phase 1 [ Time Frame: Phase 1 (9 to 24 Week Single-blind Stabilization Phase) ]

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14. Secondary:

Summary of Concomitant Medications, Phase 2 [ Time Frame: Phase 2 (52 Week Double-blind Relapse Assessment Phase) ]

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15. Secondary:

Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score [ Time Frame: Baseline, Weeks 8, 24, 36, 52 ]

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16. Secondary:

Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score [ Time Frame: Baseline, Weeks 8, 24, 36, 52 ]

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17. Secondary:

Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, [ Time Frame: Baseline, Weeks 8, 24, 36, 52 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00277212 History of Changes
Other Study ID Numbers:	CN138-392 ST
Study First Received:	January 13, 2006
Results First Received:	September 20, 2010
Last Updated:	November 16, 2010
Health Authority:	United States: Food and Drug Administration