Simulated Driving Performance, Daytime Sedation and Cognition in Healthy Volunteers Taking Gralise, Neurontin or Lyrica

Study Overview
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Brief Summary
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Phase 4, double-blind, placebo-controlled, four treatment, four sequence crossover study comparing simulated driving performance, daytime sedation and cognition in healthy volunteers administered therapeutic doses of Gralise® (Treatment A), Neurontin® (Treatment B), Lyrica® (Treatment C) and placebo (Treatment D). All doses were administered under fed conditions.

Official Title
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A Phase 4, Double-Blind, Placebo-Controlled, Crossover Study Comparing Simulated Driving Performance, Daytime Sedation, and Cognition in Healthy Volunteers Taking Therapeutic Doses of Gralise®, Neurontin®, or Lyrica®

Conditions
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Healthy

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Pregabalin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 40 and 80 years of age, inclusive. Body weight > 50 kg and BMI between 18 and 32 kg/m2, inclusive. Able to give informed consent. Licensed, experienced driver who had driven at least 3 times a week for the past 3 years and had visual acuity adequate for driving, as assessed by the investigator or designee. Able to complete a 1 hour simulated driving test and demonstrate satisfactory driving skills, as determined by the investigator or designee. Karolinska Sleep Scale (KSS) score of <=5. Other criteria apply. Exclusion Criteria: Known history of allergic reaction, hypersensitivity or clinically significant intolerance to gabapentin, pregabalin or any pharmaceutical materials, or any of the ingredients in the protocol-specified meals. Pregnant or lactating or considered at risk of pregnancy. Any medical condition or any laboratory abnormality or ECG abnormality that would, in the opinion of the investigator, contraindicate study participation. Impaired liver function (e.g., alanine aminotransferase [ALT] ≥2 times the upper limit of normal [ULN] or bilirubin ≥2 times ULN), known active hepatic disease (e.g., hepatitis), or evidence of clinically significant liver disease or other condition affecting the liver that may suggest the potential for an increased susceptibility to hepatic toxicity with oral gabapentin or pregabalin exposure. Any history of renal disease that, in the opinion of the investigator, would contraindicate study participation; or subject had significantly impaired renal function as evidenced by an estimated GFR of ≤ 80 ml/min/1.73m2. History or evidence of a sleep disorder, including sleep apnea (obstructive, central or mixed), narcolepsy or primary insomnia. Other criteria apply.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gralise® (gabapentin)<br>Gralise® 3 x 600 mg tablets (1800 mg total dose) administered once daily at 7:00 pm on Day 1 and Day 2 with one placebo capsule matching the over-encapsulation of doses of Neurontin® and Lyrica®. At other dosing times, treatment consisted of 3 placebo tablets matching the appearance of Gralise® and 1 placebo capsule. | Drug: Gabapentin<br> <br> * Other names: Gralise®, Neurontin®;|
| Active Comparator: Neurontin® (gabapentin)<br>Neurontin® 1 x 600 mg film-coated tablet administered 3 times daily at 7:00 pm on Day 1, at 8:00 am, 2:00 pm and 8:00 pm on Day 2 and at 8:00 a.m. on Day 3. Each dose of Neurontin® was over-encapsulated and administered with 3 placebo tablets matching the appearance of Gralise®. | Drug: Gabapentin<br> <br> * Other names: Gralise®, Neurontin®;|
| Active Comparator: Lyrica® (pregabalin)<br>Lyrica® 1 x 150 mg capsule administered 2 times daily at 7:00 pm on Day 1, at 8:00 am and 8:00 pm on Day 2 and at 8:00 a.m. on Day 3. Each dose of Lyrica® was over-encapsulated and administered with 3 placebo tablets matching the appearance of Gralise®. | Drug: Pregabalin<br> <br> * Other names: Lyrica®;|
| Placebo Comparator: Placebo (sugar pill)<br>Each dose consisted of 3 placebo tablets matching the appearance of Gralise® and 1 placebo capsule matching the over-encapsulation of doses of Neurontin® and Lyrica®. | Other: Placebo<br> <br> * Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Standard Deviation of the Lateral Position (SDLP) Measured on the Driving Simulator Between Gralise® and Neurontin® | SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance. | Baseline and Hour 3 on Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Standard Deviation of the Lateral Position (SDLP) Measured on the Driving Simulator Between Gralise® and Lyrica® | SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Detection Task (DET) | Cogstate - Detection Task (DET) is a simple reaction time test of Psychomotor Function. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Groton Maze Learning Test (GMLT). | Cogstate - The Groton Maze Learning test is a measure Executive Function. Total number of errors made while attempting to learn the same hidden pathway across the consecutive learning trials performed at a single assessment. Lower score means better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Identification Task (IDN). | Cogstate - Identification Task (IDN) assesses Attention. Score is speed of performance (mean of the log10 transformed reaction times for correct responses). Lower score (quicker speed) is better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - International Shopping List Test (ISL) | Cogstate - International Shopping List (ISL) test is a measure of verbal learning and uses a well-validated list-learning paradigm. Total number of correct responses remembering the word list on three consecutive trials at a single assessment. Higher score is better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - One Card Learning (OCLT). | Cogstate - The One Card Learning Test (OCLT) is a measure of visual learning and uses a well-validated pattern separation paradigm with playing card stimuli. Higher Score is better performance. Higher change from baseline means better performance. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Karolinska Sleepiness Scale (KSS). | Scale: 1-9, 1=extremely alert, 9 = very sleepy, great effort to keep awake, fighting sleep | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Portland Neurotoxicity Scale (PNS). | Portland Neurotoxicity Scale (PNS) comprises 15 questions measured on a 10-point scale. [1=No problem, 2, 3, 4, 5=Often a problem, 6, 7, 8, 9, 10=Severe problem] in 16 categories. Each question was analyzed and is presented in the same way as the primary endpoints. | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between Gralise® and Neurontin® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS). | Miles per Hour (mph) | Baseline and Hour 3 on Day 3 | 
| Change From Baseline Between Gralise® and Lyrica® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS). | Miles per Hour (mph) | Baseline and Hour 3 on Day 3 | 
| To Compare the Relative Safety and Tolerability of Gralise®, Neurontin®, and Lyrica®. | Number of subjects with Treatment-Emergent Adverse Events (TEAE) Number of subjects with Serious Adverse Event (SAE) Number of subjects discontinued due to Adverse Event (AE) | Screening to 1 week after Period 4 discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Volunteer, Pharmacodynamics, Pharmacokinetics