Trial Outcomes & Findings for Characterizing and Predicting Drug Effects on Cognition (NCT NCT01889602)
NCT ID: NCT01889602
Last Updated: 2019-12-17
Results Overview
Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
60 participants
Primary outcome timeframe
Session 1 to Session 5
Results posted on
2019-12-17
Participant Flow
Participant milestones
| Measure |
Topiramate 100mg
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Topiramate: Topiramate: 100 mg, 150 mg or 200 mg, po, 1x
|
Topiramate 150mg
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Lorazepam: Lorazepam: 2mg, po, 1x
|
Topiramate 200mg
Randomized to Topiramate; 200 mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Placebo
|
|---|---|---|---|
|
First Intervention
STARTED
|
20
|
20
|
20
|
|
First Intervention
COMPLETED
|
19
|
17
|
18
|
|
First Intervention
NOT COMPLETED
|
1
|
3
|
2
|
|
First Washout Period of at Least 2 Weeks
STARTED
|
19
|
17
|
18
|
|
First Washout Period of at Least 2 Weeks
COMPLETED
|
19
|
17
|
18
|
|
First Washout Period of at Least 2 Weeks
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Intervention
STARTED
|
19
|
17
|
18
|
|
Second Intervention
COMPLETED
|
18
|
17
|
16
|
|
Second Intervention
NOT COMPLETED
|
1
|
0
|
2
|
|
Second Washout Period of at Least 2 Week
STARTED
|
18
|
17
|
16
|
|
Second Washout Period of at Least 2 Week
COMPLETED
|
18
|
17
|
16
|
|
Second Washout Period of at Least 2 Week
NOT COMPLETED
|
0
|
0
|
0
|
|
Third Intervention
STARTED
|
18
|
17
|
16
|
|
Third Intervention
COMPLETED
|
15
|
15
|
16
|
|
Third Intervention
NOT COMPLETED
|
3
|
2
|
0
|
|
Third Washout Period of at Least 2 Weeks
STARTED
|
15
|
15
|
16
|
|
Third Washout Period of at Least 2 Weeks
COMPLETED
|
15
|
15
|
16
|
|
Third Washout Period of at Least 2 Weeks
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Topiramate 100mg
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Topiramate: Topiramate: 100 mg, 150 mg or 200 mg, po, 1x
|
Topiramate 150mg
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Lorazepam: Lorazepam: 2mg, po, 1x
|
Topiramate 200mg
Randomized to Topiramate; 200 mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Placebo
|
|---|---|---|---|
|
First Intervention
Adverse Event
|
1
|
1
|
1
|
|
First Intervention
Protocol Violation
|
0
|
1
|
1
|
|
First Intervention
Study ending
|
0
|
1
|
0
|
|
Second Intervention
Adverse Event
|
0
|
0
|
1
|
|
Second Intervention
Study ending
|
1
|
0
|
0
|
|
Second Intervention
Withdrawal by Subject
|
0
|
0
|
1
|
|
Third Intervention
Protocol Violation
|
1
|
0
|
0
|
|
Third Intervention
Withdrawal by Subject
|
2
|
2
|
0
|
Baseline Characteristics
Characterizing and Predicting Drug Effects on Cognition
Baseline characteristics by cohort
| Measure |
Topiramate 100mg
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Topiramate: Topiramate: 100 mg, 150 mg or 200 mg, po, 1x
|
Topiramate 150mg
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Lorazepam: Lorazepam: 2mg, po, 1x
|
Topiramate 200mg
n=17 Participants
Randomized to Topiramate; 200 mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
Placebo
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
46 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Continuous
|
31.9 Years
STANDARD_DEVIATION 11.48 • n=93 Participants
|
38.54 Years
STANDARD_DEVIATION 10.21 • n=4 Participants
|
26.41 Years
STANDARD_DEVIATION 8.42 • n=27 Participants
|
28.52 Years
STANDARD_DEVIATION 9.99 • n=483 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
24 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
22 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
12 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
25 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=93 Participants
|
15 participants
n=4 Participants
|
17 participants
n=27 Participants
|
46 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Session 1 to Session 5Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.
Outcome measures
| Measure |
Arm: Topiramate 100mg, Period: Topiramate
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the topiramate period.
Topiramate: 100 mg po, 1x
|
Arm:Topiramate 150mg, Period: Topiramate
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the topiramate period.
Topiramate: 150 mg po, 1x
|
Arm: Topiramate 200mg, Period: Topiramate
n=17 Participants
Randomized to Topiramate; 200mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the topiramate period.
Topiramate: 200 mg po, 1x
|
Arm: Topiramate 100mg, Period: Lorazepam
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the lorazepam period.
Lorazepam: 2 mg po, 1x
|
Arm: Topiramate 150mg, Period: Lorazepam
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the lorazepam period.
Lorazepam: 2 mg po, 1x
|
Arm: Topiramate 200mg, Period: Lorazepam
n=17 Participants
Randomized to Topiramate; 200mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the lorazepam period.
Lorazepam: 2 mg po, 1x
|
Arm: Topiramate 100mg, Period: Placebo
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the placebo period.
Placebo: po, 1x
|
Arm: Topiramate 150mg, Period: Placebo
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the placebo period.
Placebo: po, 1x
|
Arm: Topiramate 200mg, Period: Placebo
n=17 Participants
Randomized to Topiramate; 200mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the placebo period.
Placebo: po, 1x
|
|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in COWA Unique Word Count
|
-0.407725385 Word Count
Standard Deviation 0.110593408
|
-0.425898667 Word Count
Standard Deviation 0.186240451
|
-0.412534118 Word Count
Standard Deviation 0.154640084
|
-0.108298333 Word Count
Standard Deviation 0.240452491
|
0.131452143 Word Count
Standard Deviation 0.263967943
|
-0.095221176 Word Count
Standard Deviation 0.228163172
|
-0.011651538 Word Count
Standard Deviation 0.152526619
|
0.077431333 Word Count
Standard Deviation 0.176020802
|
0.047164706 Word Count
Standard Deviation 0.166162762
|
PRIMARY outcome
Timeframe: Session 1 to Session 5Study has 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). No drug was given at Sessions 1 and 5. The baseline value was defined as the average of the values at Session 1 and Session 5. The change from baseline for Topiramate is the value at 2.5 hours post-dose at the Topiramate visit minus the value at baseline, divided by the value at baseline; similarly for Lorazepam and Placebo.
Outcome measures
| Measure |
Arm: Topiramate 100mg, Period: Topiramate
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the topiramate period.
Topiramate: 100 mg po, 1x
|
Arm:Topiramate 150mg, Period: Topiramate
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the topiramate period.
Topiramate: 150 mg po, 1x
|
Arm: Topiramate 200mg, Period: Topiramate
n=17 Participants
Randomized to Topiramate; 200mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the topiramate period.
Topiramate: 200 mg po, 1x
|
Arm: Topiramate 100mg, Period: Lorazepam
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the lorazepam period.
Lorazepam: 2 mg po, 1x
|
Arm: Topiramate 150mg, Period: Lorazepam
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the lorazepam period.
Lorazepam: 2 mg po, 1x
|
Arm: Topiramate 200mg, Period: Lorazepam
n=17 Participants
Randomized to Topiramate; 200mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the lorazepam period.
Lorazepam: 2 mg po, 1x
|
Arm: Topiramate 100mg, Period: Placebo
n=14 Participants
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the placebo period.
Placebo: po, 1x
|
Arm: Topiramate 150mg, Period: Placebo
n=15 Participants
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the placebo period.
Placebo: po, 1x
|
Arm: Topiramate 200mg, Period: Placebo
n=17 Participants
Randomized to Topiramate; 200mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments. This is the placebo period.
Placebo: po, 1x
|
|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Spontaneous Narrative Raw Word Count
|
-0.01596 Word Count
Standard Deviation 0.360237984
|
-0.131732 Word Count
Standard Deviation 0.192165204
|
-0.323135625 Word Count
Standard Deviation 0.297067179
|
0.109636 Word Count
Standard Deviation 0.236323153
|
0.016635385 Word Count
Standard Deviation 0.283748379
|
-0.128177333 Word Count
Standard Deviation 0.281246222
|
0.117455385 Word Count
Standard Deviation 0.360519103
|
-0.01098 Word Count
Standard Deviation 0.272331286
|
0.011456471 Word Count
Standard Deviation 0.225720885
|
Adverse Events
Topiramate 100mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Topiramate 150mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Topiramate 200mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Lorazepam 2mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Topiramate 100mg
n=14 participants at risk
Randomized to Topiramate; 100mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
|
Topiramate 150mg
n=15 participants at risk
Randomized to Topiramate; 150mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
|
Topiramate 200mg
n=17 participants at risk
Randomized to Topiramate; 200 mg; lorazepam 2mg or placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
|
Lorazepam 2mg
n=46 participants at risk
Randomized to Topiramate; 100, 150, or 200 mg; lorazepam 2mg; Each subject in this arm received each treatment in random order with a two-week washout between treatments
|
Placebo
n=46 participants at risk
Randomized to Topiramate; 100, 150, or 200 mg; placebo; Each subject in this arm received each treatment in random order with a two-week washout between treatments
|
|---|---|---|---|---|---|
|
Eye disorders
Eye Twitching
|
0.00%
0/14 • 30 days following the last administration of study drug.
Study is a 3x3 latin square design with 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). Sessions 1 and 5 are washouts.
|
0.00%
0/15 • 30 days following the last administration of study drug.
Study is a 3x3 latin square design with 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). Sessions 1 and 5 are washouts.
|
5.9%
1/17 • Number of events 1 • 30 days following the last administration of study drug.
Study is a 3x3 latin square design with 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). Sessions 1 and 5 are washouts.
|
0.00%
0/46 • 30 days following the last administration of study drug.
Study is a 3x3 latin square design with 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). Sessions 1 and 5 are washouts.
|
0.00%
0/46 • 30 days following the last administration of study drug.
Study is a 3x3 latin square design with 3 arms (100mg, 150mg, or 200mg topiramate) and 3 periods per arm (topiramate, 2mg lorazepam, or placebo). Topiramate (TPM), Lorazepam (LZP), or Placebo (PLA) was given to the participant at the beginning of Sessions 2, 3, and 4 (crossover design). Sessions 1 and 5 are washouts.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place