Trial Outcomes & Findings for Efficacy and Tolerability of Topiramate in Treatment of Bipolar Mania and Alcohol Use in Adolescents and Young Adults (NCT NCT00550394)

Results Overview

Change in self-reported drinks/day (drinks consumed divided by the number of days during that study period).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

56 participants

Primary outcome timeframe

baseline to 12 weeks or endpoint (up to 11 weeks)

Results posted on

2017-05-23

Participant Flow

56 study participants were consented for study participation, of which 17 were screen fails.

Participant milestones

Participant milestones
Measure	Quetiapine and Placebo Quetiapine and Placebo quetiapine and placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine and Topiramate Quetiapine and Topiramate Quetiapine and Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Overall Study STARTED	21	18
Overall Study COMPLETED	9	5
Overall Study NOT COMPLETED	12	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Tolerability of Topiramate in Treatment of Bipolar Mania and Alcohol Use in Adolescents and Young Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Quitiapine and Placebo n=21 Participants Quetiapine and Placebo quetiapine and placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quitiapine andTopiramate n=18 Participants Quetiapine and Topiramate Quetiapine andTopiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	21 Participants n=5 Participants	18 Participants n=7 Participants	39 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	18 years STANDARD_DEVIATION 3.1 • n=5 Participants	17.7 years STANDARD_DEVIATION 2.4 • n=7 Participants	17.9 years STANDARD_DEVIATION 2.7 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	8 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	18 participants n=7 Participants	39 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline to 12 weeks or endpoint (up to 11 weeks)

Change in self-reported drinks/day (drinks consumed divided by the number of days during that study period).

Outcome measures

Outcome measures
Measure	Quetiapine + Placebo n=21 Participants Quetiapine + Placebo quetiapine + placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine + Topiramate n=18 Participants Quetiapine + Topiramate Quetiapine + Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Drinks Per Day	-1.4 Drinks per day Standard Deviation 2.3	-2.4 Drinks per day Standard Deviation 5.1

PRIMARY outcome

Timeframe: baseline to 12 weeks or endpoint (up to 11 weeks)

Change in drinks/drinking day (number of drinks consumed divided by the number of days during which alcohol was consumed during that study period)

Outcome measures

Outcome measures
Measure	Quetiapine + Placebo n=21 Participants Quetiapine + Placebo quetiapine + placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine + Topiramate n=18 Participants Quetiapine + Topiramate Quetiapine + Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Drinks Per Drinking Day	-7.2 Drinks per drinking day Standard Deviation 10.2	-7.3 Drinks per drinking day Standard Deviation 6.0

PRIMARY outcome

Timeframe: baseline to 12 weeks or endpoint (up to 11 weeks)

Change in percent days abstinent (the number of non-drinking days divided by the number of days in that study period).

Outcome measures

Outcome measures
Measure	Quetiapine + Placebo n=21 Participants Quetiapine + Placebo quetiapine + placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine + Topiramate n=18 Participants Quetiapine + Topiramate Quetiapine + Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Percentage of Days Abstinent	15 Percentage of days abstinent Standard Deviation 19	14 Percentage of days abstinent Standard Deviation 23

PRIMARY outcome

Timeframe: baseline to 12 weeks or endpoint (up to 11 weeks)

Change in percent heavy drinking days (number of days of \> 4 drinks/day divided by number of days in that study period).

Outcome measures

Outcome measures
Measure	Quetiapine + Placebo n=21 Participants Quetiapine + Placebo quetiapine + placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine + Topiramate n=18 Participants Quetiapine + Topiramate Quetiapine + Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Percent Heavy Drinking Days	-10 Percent heavy drinking days Standard Deviation 19	-14 Percent heavy drinking days Standard Deviation 25

Adverse Events

Quetiapine and Placebo

Serious events: 8 serious events

Other events: 4 other events

Deaths: 0 deaths

Quetiapine and Topiramate

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Quetiapine and Placebo n=21 participants at risk Quetiapine and Placebo quetiapine + placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine and Topiramate n=18 participants at risk Quetiapine and Topiramate Quetiapine + Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
General disorders Suicidal ideation	33.3% 7/21 • 3 years 9 months	11.1% 2/18 • 3 years 9 months
General disorders Suicide Attempt	4.8% 1/21 • 3 years 9 months	0.00% 0/18 • 3 years 9 months

Other adverse events

Other adverse events
Measure	Quetiapine and Placebo n=21 participants at risk Quetiapine and Placebo quetiapine + placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.	Quetiapine and Topiramate n=18 participants at risk Quetiapine and Topiramate Quetiapine + Topiramate: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
General disorders sedation	19.0% 4/21 • 3 years 9 months	61.1% 11/18 • 3 years 9 months
General disorders Difficulty Arousing	14.3% 3/21 • 3 years 9 months	50.0% 9/18 • 3 years 9 months

Additional Information

Melissa DelBello, MD, MS

University of Cincinnati

Phone: 513-558-2989

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place