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

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®

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Drug: Gabapentin; Drug: Pregabalin

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Gralise® (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.	Drug: Gabapentin; Other Names: Gralise®, Neurontin®
ACTIVE_COMPARATOR: Neurontin® (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®.	Drug: Gabapentin; Other Names: Gralise®, Neurontin®
ACTIVE_COMPARATOR: Lyrica® (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®.	Drug: Pregabalin; Other Names: Lyrica®
PLACEBO_COMPARATOR: Placebo (sugar pill); 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; Other Names: Sugar Pill

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Depomed

Publications and helpful links

General Publications

• Schmidt P, Rao S. Effects of gabapentin, pregabalin and gastroretentive gabapentin on simulated driving, daytime sedation and cognition. Pain Manag. 2018 Jul 1;8(4):297-306. doi: 10.2217/pmt-2018-0005. Epub 2018 Apr 19.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 24, 2015
• Primary Completion (ACTUAL): November 20, 2015
• Study Completion (ACTUAL): November 20, 2015

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (ACTUAL): June 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2020
• Last Update Submitted That Met QC Criteria: May 15, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pharmacodynamics; Volunteer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Gabapentin; Pregabalin
• Other Study ID Numbers: GRAL-PX-8401