Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This will be a randomized, double-blind, placebo- controlled cross-over study to investigate the effect of GEn on cardiac repolarisation parameters compared with placebo and a positive control, moxifloxacin. Approximately 52 subjects will be recruited to the study and will take part in four dosing sessions. Subjects will receive, in a randomized order, a single dose of 1200 mg GEn, 6000 mg GEn (supratherapeutic dose), 400 mg moxifloxacin (positive control) and placebo. Twelve lead continuous ECG monitoring will be conducted from pre-dose to approximately 24 hours after dosing on Day 1 of each study session. The primary comparison of interest will be the mean change from baseline in the time-matched differences in QTcF between each GEn treatment and placebo.
This is a 4-period, randomized, active-and placebo-controlled, double-dummy, double-blind cross-over study to evaluate the effect of single doses of GEn on cardiac conduction parameters in healthy subjects.
Screening will occur within approximately 28 days of the first scheduled dose of study medication. Each subject will participate in 4 dosing sessions at least one week apart. Prior to dosing in each period, the investigator will review the scheduled assessments to confirm the subject's suitability for the study including review of study entry criteria and lifestyle restrictions.
All subjects will receive single doses of GEn 1200 mg, GEn 6000 mg, moxifloxacin 400 mg and placebo in a randomized sequence.
Dosing with moxifloxacin will be in the fasted state and GEn will be administered following a standard meal. A double dummy approach will be used to maintain blinding. Thus, on each dosing day, moxifloxacin or moxifloxacin placebo will be administered in the fasted state in the morning and GEn or matched placebo will be administered 2 hours later after a standard meal.
During each treatment period, subjects will report to the clinical research unit the day before dosing (Day 1) and will remain until completion of the last assessment on Day 2. Twelve-lead ECGs including continuous Holter monitoring, clinical laboratory safety tests, vital sign measurements, physical examinations, adverse event reports, and pharmacokinetic samples will be collected throughout the study.
In each study period, cardiac conduction will be measured using a 24-hour continuous 12-lead Holter monitor from the morning of Day 1 until the morning of Day 2. Extraction of the Holter monitor data in triplicate for analysis will begin on Day 1 at timepoints indicated in the Time and Events Table (Section 4.7). These timepoints were selected to cover the Cmax of both moxifloxacin and GEn. If no clinically significant abnormalities are noted, subjects will be discharged from the clinical research unit after the completion of all assessments on Day 2 in each period. A minimum 7-day washout period will separate each treatment period. A follow-up visit will be conducted approximately 7 to 14 days after administration of the last dose of study medication in treatment period 4
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment 1 | Experimental | Healthy Volunteers will receive Treatments ABDC |
|
| Treatment 2 | Experimental | Healthy Volunteers will receive Treatments BCAD |
|
| Treatment 3 | Experimental | Healthy Volunteers will receive Treatments CDBA |
|
| Treatment 4 | Experimental | Healthy Volunteers will receive Treatments DACB |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GEn 1200mg | Drug | 1200 mg of Gen administered as a single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in QTcF (QT duration corrected for heart rate by Fridericia's formula) interval at Each time point for 6000 mg GEn and Placebo measured by ECG | Day -1-Day2 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in QTcF interval at Each time point for 1200 mg GEn and Placebo measured by ECG | Day -1-Day 2 | |
| Change from baseline in QTcF interval at each time point for moxifloxacin 400 mg and placebo measured by ECG | Day -1-Day 2 |
Not provided
Inclusion Criteria:
Body weight greater than and equal to 50 kg and BMI within the range 19 - 30 kg/m2 (inclusive)
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Austin | Texas | 78744 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24290737 | Derived | Davy M, Upward J, Arumugham T, Twomey C, Chen C, Stier B. Cardiac repolarization with Gabapentin enacarbil in a randomized, double-blind, placebo- and active-controlled, crossover thorough QT/QTc study in healthy adults. Clin Ther. 2013 Dec;35(12):1964-74. doi: 10.1016/j.clinthera.2013.10.011. Epub 2013 Nov 28. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012148 | Restless Legs Syndrome |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D045565 | Holliday Junction Resolvases |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D004706 | Endodeoxyribonucleases |
| D003851 | Deoxyribonucleases |
| D004950 | Esterases |
| D006867 | Hydrolases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Gen 6000 mg | Drug | 6000 mg of Gen administered as a single dose |
|
|
| GEn Placebo | Drug | Placebo to match GEn Tablets |
|
| Moxifloxacin Placebo | Drug | Placebo to match Moxifloxacin |
|
| Moxifloxacin | Drug | 400 mg Moxifloxacin administered as a single dose |
|
|
| Change from baseline in QTcB (QT duration corrected for heart rate by Bazett's formula), QT for GEn (1200 mg and 6000 mg) and moxifloxacin (400 mg) and placebo measured by ECG | Day -1-Day 2 |
| Change from baseline in PR, QRS intervals, heart rate and ECG waveform morphology for GEn (1200 mg and 6000 mg) and placebo measured by ECG | Day -1-Day 2 |
| Change from baseline in heart rate and ECG waveform morphology for moxifloxacin (400 mg) | Day -1-Day 2 |
| Pharmacokinetic parameters for gabapentin and moxifloxacin | Day -1-Day 2 |
| Safety parameters: AEs, vital signs, ECGs, Columbia Suicide Severity Rating Scale (C-SSRS) and clinical laboratory parameters | Day -1-Day 2 |
| D020447 |
| Parasomnias |
| D001523 | Mental Disorders |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D004720 | Endonucleases |
| D045522 | Recombinases |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |