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

Phase 4

Completed

Conditions: Healthy

Interventions: Other: Placebo
Drug: Pregabalin
Drug: Gabapentin

Registration Number: NCT03179345

Lead Sponsor: Depomed

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo (sugar pill)	Placebo	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®.
Lyrica® (pregabalin)	Pregabalin	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®.
Neurontin® (gabapentin)	Gabapentin	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®.
Gralise® (gabapentin)	Gabapentin	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Detection Task (DET)	Baseline and Hour 3 on Day 3	Cogstate - Detection Task (DET) is a simple reaction time test of Psychomotor Function. Higher change from baseline means better performance.
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Groton Maze Learning Test (GMLT).	Baseline and Hour 3 on Day 3	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.
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Karolinska Sleepiness Scale (KSS).	Baseline and Hour 3 on Day 3	Scale: 1-9, 1=extremely alert, 9 = very sleepy, great effort to keep awake, fighting sleep
Change From Baseline Between Gralise® and Neurontin® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS).	Baseline and Hour 3 on Day 3	Miles per Hour (mph)
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - Identification Task (IDN).	Baseline and Hour 3 on Day 3	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.
Change From Baseline Between Gralise® and Lyrica® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS).	Baseline and Hour 3 on Day 3	Miles per Hour (mph)
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - One Card Learning (OCLT).	Baseline and Hour 3 on Day 3	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.
To Compare the Relative Safety and Tolerability of Gralise®, Neurontin®, and Lyrica®.	Screening to 1 week after Period 4 discharge	* 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)
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Cognitive Evaluation of Cogstate - International Shopping List Test (ISL)	Baseline and Hour 3 on Day 3	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.
Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Lyrica®	Baseline and Hour 3 on Day 3	SDLP (feet): This is a measurement of change from maintaining the normal driving position in the lane over time and / or distance.
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Portland Neurotoxicity Scale (PNS).	Baseline and Hour 3 on Day 3	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.