Trial Outcomes & Findings for Levetiracetam in the Management of Bipolar Depression (NCT NCT00566150)

Last Updated: 2020-03-31

Results Overview

Change is observed value at each visit minus baseline value. HDRS-21 is a 21-item instrument measuring depression. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 60.

Recruitment status

COMPLETED

Study phase

Target enrollment

35 participants

Primary outcome timeframe

Baseline to week 6

Results posted on

2020-03-31

Participant Flow

Subjects were recruited from 2005-2008 from New Haven, CT and surrounding areas.

Participant milestones

Participant milestones
Measure	Levetiracetam Subjects on active study medication.	Placebo Subjects assigned to placebo control group.
Overall Study STARTED	19	16
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	9	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Levetiracetam in the Management of Bipolar Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Levetiracetam n=19 Participants Subjects on active study medication.	Placebo n=16 Participants Subjects assigned to placebo control group.	Total n=35 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	45.5 years STANDARD_DEVIATION 10.7 • n=5 Participants	42.4 years STANDARD_DEVIATION 9.6 • n=7 Participants	44.1 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to week 6

Population: Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.

Outcome measures

Outcome measures
Measure	Levetiracetam n=17 Participants Subjects on active study medication.	Placebo n=15 Participants Subjects assigned to placebo control group.
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. Week 1 (n=17, n=15)	-2.7647 score on scale Standard Error 1.4138	-4 score on scale Standard Error 1.5051
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. Week 2 (n=15, n=14)	-3.4259 score on scale Standard Error 1.4618	-6.5875 score on scale Standard Error 1.5327
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. Week 3 (n=13, n=14)	-2.1243 score on scale Standard Error 1.5441	-6.3625 score on scale Standard Error 1.5458
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. Week 4 (n=11, n=13)	-4.3534 score on scale Standard Error 1.6582	-6.3851 score on scale Standard Error 1.583
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. Week 5 (n=11, n=13)	-6.952 score on scale Standard Error 1.7105	-6.4368 score on scale Standard Error 1.6006
Change in Hamilton Depression Rating Scale (HDRS-21) Total Score From Baseline at Week 6. Week 6 (n=10, n=11)	-4.8136 score on scale Standard Error 1.7806	-7.0712 score on scale Standard Error 1.6838

SECONDARY outcome

Timeframe: Baseline to week 6

Population: Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.

Change is observed value at each visit minus baseline value. MADRS is a 10-item instrument measuring depression: scale range between 0(normal) - 6(most abnormal)for each item. Total possible score is 0 - 60.

Outcome measures

Outcome measures
Measure	Levetiracetam n=17 Participants Subjects on active study medication.	Placebo n=15 Participants Subjects assigned to placebo control group.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. Week 5 (n=11, n=12)	-9.9142 score on scale Standard Error 2.3441	-6.6591 score on scale Standard Error 2.3061
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. Week 1 (n=17, n=15)	-3.2941 score on scale Standard Error 2.0145	-2.7333 score on scale Standard Error 2.1446
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. Week 2 (n=15, n=14)	-5.2319 score on scale Standard Error 2.1105	-7.256 score on scale Standard Error 2.1999
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. Week 3 (n=13, n=14)	-3.384 score on scale Standard Error 2.2162	-9.0417 score on scale Standard Error 2.1999
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. Week 4 (n=11, n=13)	-5.5505 score on scale Standard Error 2.3441	-8.7608 score on scale Standard Error 2.2514
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Baseline at Week 6. Week 6 (n=10, n=11)	-6.5208 score on scale Standard Error 2.4183	-4.5153 score on scale Standard Error 2.3691

SECONDARY outcome

Timeframe: Week 6

Remission response is measured as an HDRS-21 total score is less than or equal to 7. HDRS-21 measures range of depressive symptoms. Endpoint is LOCF.

Outcome measures

Outcome measures
Measure	Levetiracetam n=17 Participants Subjects on active study medication.	Placebo n=15 Participants Subjects assigned to placebo control group.
Number of Subjects Who Achieve Remission. Remitted	0 Participants	4 Participants
Number of Subjects Who Achieve Remission. Not remitted	17 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline to week 6

Population: Weeks 1-6 are Intent to treat (ITT) population Observed Cases. All participants included received at least 1 dose of study intervention and at least 1 assessment post-baseline.

Change is observed value at each visit minus baseline value. CGI-BP depression severity is an instrument which measures severity of depression in bipolar disorder. Scale range: 1=normal, not ill; 7=very severely ill

Outcome measures

Outcome measures
Measure	Levetiracetam n=17 Participants Subjects on active study medication.	Placebo n=15 Participants Subjects assigned to placebo control group.
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. Week 6 (n=10, n=10)	-0.5742 score on scale Standard Error 0.2539	-0.9294 score on scale Standard Error 0.2505
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. Week 1 (n=17, n=15)	-0.2941 score on scale Standard Error 0.1982	-0.4667 score on scale Standard Error 0.211
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. Week 2 (n=14, n=14)	-0.3186 score on scale Standard Error 0.211	-0.6956 score on scale Standard Error 0.2161
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. Week 3 (n=13, n=14)	-0.1984 score on scale Standard Error 0.2207	-0.7753 score on scale Standard Error 0.2177
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. Week 4 (n=11, n=13)	-0.3729 score on scale Standard Error 0.2386	-0.8403 score on scale Standard Error 0.2238
Change in Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) Depression Severity Rating From Baseline at Week 6. Week 5 (n=11, n=12)	-0.7325 score on scale Standard Error 0.244	-0.8739 score on scale Standard Error 0.2322

Adverse Events

Levetiracetam

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Zubin Bhagwagar

Yale University

Phone: 203-974-7560

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Levetiracetam n=19 participants at risk Subjects on active study medication.	Placebo n=16 participants at risk Subjects assigned to placebo control group.
Nervous system disorders Somnolence	52.6% 10/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	43.8% 7/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Gastrointestinal disorders GI symptoms	31.6% 6/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	31.2% 5/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Irritability	26.3% 5/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Coordination	21.1% 4/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Shakiness	10.5% 2/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	12.5% 2/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Dizziness	15.8% 3/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	12.5% 2/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Weakness	15.8% 3/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Headache	15.8% 3/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	37.5% 6/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Gastrointestinal disorders Dry mouth	10.5% 2/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	12.5% 2/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Hypomanic symptoms	10.5% 2/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Worsening of depressive symptoms	10.5% 2/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Insomnia	5.3% 1/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Slurred speech	5.3% 1/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Sunstance Abuse Relapse	10.5% 2/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Increase in suicidality	5.3% 1/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Psychiatric disorders Cognitive	5.3% 1/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Gastrointestinal disorders Drooling	5.3% 1/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
General disorders Genitourinary	5.3% 1/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	0.00% 0/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Nervous system disorders Blurred vision	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
General disorders Unusual dreams/nightmares	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Gastrointestinal disorders Taste	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
General disorders Nosebleed	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Cardiac disorders Cardiac	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Musculoskeletal and connective tissue disorders Rash	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
Musculoskeletal and connective tissue disorders Muscle soreness	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	6.2% 1/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.
General disorders Cold	0.00% 0/19 • Adverse events were collected during course of the study and for two weeks after last study intervention.	12.5% 2/16 • Adverse events were collected during course of the study and for two weeks after last study intervention.