HealthyPhase 4NCT03179345

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

A Phase 4 study testing Gabapentin and Pregabalin in people with Healthy, run by Depomed.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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). Read more about this study

Who is it for?: Ages 40 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Gabapentin and Pregabalin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 32 participants
Where: No sites listed yet
Study dates: 24 Sep 2015to 20 Nov 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

About this study

Official title: 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: Healthy
Being tested: Gabapentin, Pregabalin, Placebo
Keywords: Volunteer, Pharmacodynamics, Pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GabapentinDrug
Also called Gralise®, Neurontin®
PregabalinDrug
Also called Lyrica®
PlaceboOther
Also called Sugar Pill

Study groups in NCT03179345
Study group	Role	What they receive
Gralise® (gabapentin)	Active comparator	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. Receives: Drug: Gabapentin
Neurontin® (gabapentin)	Active comparator	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®. Receives: Drug: Gabapentin
Lyrica® (pregabalin)	Active comparator	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®. Receives: Drug: Pregabalin
Placebo (sugar pill)	Placebo comparator	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®. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Hour 3 on Day 3

Secondary outcomes (11)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Screening to 1 week after Period 4 discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Sep 201520 Nov 2015

First posted7 Jun 2017
Study start24 Sep 2015
Primary completion20 Nov 2015
Study completion20 Nov 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03179345
Sponsor's protocol ID: GRAL-PX-8401
Status last verified: Apr 2020
First submitted: 5 Jun 2017
Last updated: 1 Jun 2020
Results posted: Yes, on ClinicalTrials.gov

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.
PubMed 29671676

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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®
ClinicalTrials.gov ID: NCT03179345
Acronym / sponsor ID: GRAL-PX-8401
Conditions: Healthy
Keywords: Volunteer, Pharmacodynamics, Pharmacokinetics
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: DepomedIndustry (pharma, biotech, devices)
Study start: 24 Sep 2015 (actual)
Primary completion: 20 Nov 2015 (actual)
Study completion: 20 Nov 2015 (actual)
First posted: 7 Jun 2017 (actual)
Results: Posted 13 May 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Number of arms: 4

Arm	Type	Receives
Gralise® (gabapentin)	Active comparator	Drug: GabapentinGralise® 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.
Neurontin® (gabapentin)	Active comparator	Drug: GabapentinNeurontin® 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®.
Lyrica® (pregabalin)	Active comparator	Drug: PregabalinLyrica® 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®.
Placebo (sugar pill)	Placebo comparator	Other: PlaceboEach 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®.

Who may qualify

Ages: 40 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GabapentinAlso: Gralise®, Neurontin®	Drug	Gralise® (gabapentin), Neurontin® (gabapentin)
PregabalinAlso: Lyrica®	Drug	Lyrica® (pregabalin)
PlaceboAlso: Sugar Pill	Other	Placebo (sugar pill)

Primary outcome

Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Neurontin®
Time frame: 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.

11 secondary outcomes

Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Lyrica®
Time frame: 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)
Time frame: 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).
Time frame: 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).
Time frame: 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)
Time frame: 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).
Time frame: Baseline and Hour 3 on Day 3
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Karolinska Sleepiness Scale (KSS).
Time frame: Baseline and Hour 3 on Day 3
Change From Baseline Between, Gralise® and Neurontin®, Gralise® and Lyrica® for Sedation Evaluation - Portland Neurotoxicity Scale (PNS).
Time frame: Baseline and Hour 3 on Day 3
Change From Baseline Between Gralise® and Neurontin® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS).
Time frame: Baseline and Hour 3 on Day 3
Change From Baseline Between Gralise® and Lyrica® in the Driving Simulator - Standard Deviation of Vehicle Speed (SDVS).
Time frame: Baseline and Hour 3 on Day 3
To Compare the Relative Safety and Tolerability of Gralise®, Neurontin®, and Lyrica®.
Time frame: Screening to 1 week after Period 4 discharge

Results and safety

Results posted to the registry on 13 May 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Gral First, Then Neur, Lyr, and Plbo	8	8
Neur First, Then Plbo, Gral, and Lyr	8	7
Lyr First, Then Gral, Plbo, and Neur	8	7
Plbo First, Then Lyr, Neur, and Gral	8	6

Primary outcome: Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Neurontin®

Time frame: Baseline and Hour 3 on Day 3. Least squares mean (Standard Error). Unit: feet

Measure	Gralise® (Gabapentin) n = 28	Neurontin® (Gabapentin) n = 31	Placebo n = 30
Value	0.255 (0.0781)	0.395 (0.0763)	0.135 (0.0770)

Gralise® (Gabapentin) vs Neurontin® (Gabapentin): Mean Difference (Net): -0.141 (95% CI -0.266 to -0.016), p = 0.0275, ANOVA
Gralise® (Gabapentin) vs Placebo: Mean Difference (Net): 0.120 (95% CI -0.006 to 0.245), p = 0.0611, ANOVA

Population analysed: The above is the only Primary Outcome Measure (comparing the SDLP between Gralise® and Neurontin®).

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: 7 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gralise® (Gabapentin)	0 of 28 (0%)	6 of 28 (21.4%)	Not reported
Neurontin® (Gabapentin)	0 of 31 (0%)	11 of 31 (35.5%)	Not reported
Lyrica® (Pregabalin)	0 of 31 (0%)	14 of 31 (45.2%)	Not reported
Placebo (Sugar Pill)	0 of 30 (0%)	2 of 30 (6.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29671676Schmidt 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Head of R&D study director

Depomed

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Gabapentin and Pregabalin in people with Healthy, run by Depomed.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the "Standard Deviation of the Lateral Position" (SDLP) Measured on the Driving Simulator Between Gralise® and Neurontin® (time frame: Baseline and Hour 3 on Day 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03179345, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2020.