The purpose of this study is to determine how much lorazepam gets into the blood and how long it takes the body to get rid of it when given together with LY2216684. Information about any side effects that may occur will also be collected.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
28
For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
Leeds, United Kingdom
Pharmacokinetics of Lorazepam, Maximum Plasma Concentration (Cmax)
The geometric least squares mean and 90% Confidence Interval are presented. Geometric least squares mean corrected for participant, treatment and random error.
Time frame: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose
Pharmacokinetics of Lorazepam, Time to Maximum Plasma Concentration (Tmax)
Time frame: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose
Pharmacokinetics of Lorazepam, Area Under the Plasma Concentration Curve (AUC) From Time 0 to Infinity (∞)
The geometric least squares mean and 90% Confidence Interval are presented. Geometric least squares mean corrected for participant, treatment and random error.
Time frame: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post lorazepam dose
Change From Baseline in Cognitive Function-Simple Reaction Time
Participants were instructed to press the 'Yes' response button as quickly as possible every time the word 'Yes' was presented on the computer screen. Fifty stimuli were presented with a varying inter-stimulus interval of between 1 and 3.5 seconds. Participant's reaction time to the stimulus was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit Vigilance Targets Detected
A target digit was pseudo-randomly selected and constantly displayed to the right of the computer screen. A series of 450 digits was then presented in the center of the computer screen at the rate of 150 per minute. The participant was required to press the 'Yes' button as quickly as possible every time a digit in the series matched the target digit. There were 45 targets. Percentage of target digits correctly detected was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
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Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit Vigilance Speed
A target digit was pseudo-randomly selected and constantly displayed to the right of the computer screen. A series of 450 digits was then presented in the center of the computer screen at the rate of 150 per minute. The participant was required to press the 'Yes' button as quickly as possible every time a digit in the series matched the target digit. There were 45 targets. Speed at which a participant detected target digits was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Digit False Alarms
A target digit was pseudo-randomly selected and constantly displayed to the right of the computer screen. A series of digits were then presented in the center of the computer screen at the rate of 150 per minute. The participant was required to press the 'Yes' button as quickly as possible every time a digit in the series matched the target digit. There were 45 targets. The number of false alarms (incorrect 'Yes' responses) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Choice Reaction Time
Participants were required to respond to the words 'Yes' and 'No' as they appeared on the computer screen by pressing the corresponding button as quickly as possible. There were 50 trials during which each stimulus word was chosen randomly with equal probability; there was a varying inter-stimulus interval of between 1 and 3.5 seconds. The time required to respond was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Choice Reaction Time Accuracy
Participants were required to respond to the words 'Yes' and 'No' as they appeared on the computer screen by pressing the corresponding button as quickly as possible. There were 50 trials during which each stimulus word was chosen randomly with equal probability; there was a varying inter-stimulus interval of between 1 and 3.5 seconds. The percentage of correct responses was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Numeric Working Memory Sensitivity Index (SI)
Working memory is a sum of accuracy measures from the numeric and spatial working memory tasks (sensitivity index \[SI\]). Working Memory SI is based on how fast the participant responds correctly and how many are correct responses. A high score reflects someone able to hold in memory for a prolonged period. A negative change from baseline reflects impairment compared to baseline. A series of 5 digits were presented on a computer screen, one every 1.15 seconds, for the participant to hold in memory. This was followed by a series of 30 probe digits for each of which the participant had to decide whether it had appeared in the original series of digits and press the corresponding 'Yes' or 'No' response button as quickly as possible. This procedure was repeated 2 times using 2 different series and probes. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Numeric Working Memory Speed
A series of 5 digits were presented on a computer screen, one every 1.15 seconds, for the participant to hold in memory. This was followed by a series of 30 probe digits for each of which the participant had to decide whether it had appeared in the original series of digits and press the corresponding 'Yes' or 'No' response button as quickly as possible. This procedure was repeated a further 2 times using 2 different series and probes. The time required to press the corresponding 'Yes' or 'No' response button in response to the probe digit is presented. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Immediate Word Recall Accuracy
The participant was given a series of words to commit to memory. Immediately after the last word was presented, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The percentage of words correctly recalled (present on the original list of words) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Immediate Word Recall Errors
The participant was given a series of words to commit to memory. Immediately after the last word was presented, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The number of words incorrectly recalled (not on the original list of words) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Delayed Word Recall Accuracy
The participant was given a series of words to commit to memory. After a delay of approximately 15-20 minutes, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The percentage of words correctly recalled (present on the original list of words) was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Delayed Word Recall Errors
The participant was given a series of words to commit to memory. After a delay, the participant was given 1 minute to write as many of the words as possible in any order on a sheet of paper. The number of incorrect words was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Word Recognition Sensitivity Index (SI)
Word Recognition SI is based on how fast the participant responds correctly and how many are correct responses. SI ranging from zero (chance performance) to one (perfect accuracy). Higher SI indicates better cognitive function. A negative change from baseline reflects impairment compared to baseline. The original words from Word Presentation plus 15 distractor words were presented one at a time in a randomized order. For each word, the participant was required to indicate whether they recognized it from the original list of words by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following each response, there was a delay of 1 second before the next word was presented. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Word Recognition Speed
The original words from Word Presentation plus 15 distractor words were presented one at a time in a randomized order. For each word, the participant was required to indicate whether they recognized it from the original list of words by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following each response, there was a delay of 1 second before the next word was presented. The time required to press the corresponding 'Yes' or 'No' response button in response to the word was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Picture Recognition Sensitivity Index (SI)
Picture Recognition SI is based on how fast the participant responds correctly and how many are correct responses. SI ranging from zero (chance performance) to one (perfect accuracy). Higher SI indicates better cognitive function. A negative change from baseline reflects impairment compared to baseline. The original pictures from Picture Presentation plus 20 distractor pictures were presented one at a time. For each picture, the participant was required to indicate whether they recognized it from the original series of pictures by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following the response, there was a delay of 1 second before the next pictures was presented. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Picture Recognition Speed
The original pictures from Picture Presentation plus 20 distractor pictures were presented one at a time. For each picture, the participant was required to indicate whether they recognized it from the original series of pictures by pressing the corresponding 'Yes' or 'No' button as quickly as possible. Following the response, there was a delay of 1 second before the next pictures was presented. The time required to press the corresponding 'Yes' or 'No' response button in response to the picture was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Tracking Average Distance From Target
The participant used a joystick to track a randomly moving target on the computer screen. The distance from the target was measured. Participant's response was measured twice. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Postural Stability
The ability to stand upright without moving was assessed using equipment modeled on the Wright Ataxia-meter. To measure movements, a cord was attached to the participant who was required to stand for one minute, as still as possible, with feet apart and eyes closed. The amount of sway is expressed as the total angular movement calibrated in units of one-third degree of angle of sway. The amount of sway is expressed as the total angular movement in the antero-posterior plane and calibrated in units of one-third degree of angle of sway. Higher result indicates better postural stability. A negative change from baseline reflects impairment compared to baseline. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Alertness
The participant was required to rate how they felt "at this moment" on sixteen 10 centimeter visual analogue scales. The scale endpoints were anchored using polar word pairs such as 'drowsy-alert', 'clumsy-well coordinated', 'mentally slow-quick witted' and 'incompetent-proficient'. Responses from the 16 scales were scored to yield 3 main factors: Self-rated Alertness, Self-rated Contentment, and Self-rated Calmness. The possible range of scores are 0 to 100 for each factor and are represented in millimeters on the 10 centimeter line with higher numbers indicating greater alertness. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Contentment
The participant was required to rate how they felt "at this moment" on sixteen 10 centimeter visual analogue scales. The scale endpoints were anchored using polar word pairs such as 'drowsy-alert', 'clumsy-well coordinated', 'mentally slow-quick witted' and 'incompetent-proficient'. Responses from the 16 scales were scored to yield 3 main factors: Self-rated Alertness, Self-rated Contentment, and Self-rated Calmness. The possible range of scores are 0 to 100 for each factor and are represented in millimeters on the 10 centimeter line with higher numbers indicating greater contentment. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3
Change From Baseline in Cognitive Function-Self-rated Calmness
The participant was required to rate how they felt "at this moment" on sixteen 10 centimeter visual analogue scales. The scale endpoints were anchored using polar word pairs such as 'drowsy-alert', 'clumsy-well coordinated', 'mentally slow-quick witted' and 'incompetent-proficient'. Responses from the 16 scales were scored to yield 3 main factors: Self-rated Alertness, Self-rated Contentment, and Self-rated Calmness. The possible range of scores are 0 to 100 for each factor and are represented in millimeters on the 10 centimeter line with higher numbers indicating greater calmness. Least squares means were adjusted for baseline, period, sequence, time, treatment and treatment\*time.
Time frame: Baseline, 2, 4, 8 hours on Day 3