- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01849003
Study of the Effect of GS-6615 in Subjects With LQT-3
An Open-label Study to Evaluate the Effect of Single Dose GS-6615 on QT, Safety and Tolerability in Subjects With Long QT-3 Syndrome
This mechanism of action study is to evaluate the effect of oral GS-6615 on the QTc interval in participants with Long QT-3 syndrome. This study will be performed in six cohorts of participants in a sequential manner, four single-dose cohorts followed by two multiple-dose cohorts. Duration of treatment for the single-dose cohorts and multiple-dose cohorts will be 1 day and 7 days, respectively. Participants will be confined at the study center from check-in until completion of assessments at discharge.
Participants will be continuously monitored using real-time telemetry throughout the in-clinic confinement. Physical examinations including vital signs, laboratory analysis, electrocardiograms (ECGs), Holter recordings and echocardiography (ECHO) will be performed at defined time points throughout the study period. Assessment of adverse events and concomitant medications will continue throughout the duration of the study.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
Rochester, New York, United States, 14620
- University of Rochester Medical Center/Strong Memorial Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Males and females between ages 18-65 years (inclusive) at time of screening
- Documented LQT-3 genotype with one of the following mutations: delta KPQ, R1623Q, N1325S, E1784K, S1787N, D1790G, G1631D, 1795insD, delF1617, R1644H, L409P, F2004L, I1768V, T1304M, A1330T, or F1596I3.
- QTc > 480 msec in lead V5 at screening
- Weight of at least 50 kg with body mass index (BMI) between 18 and 30 kg/m^2 (inclusive)
- Females of childbearing potential must have a negative serum pregnancy test at screening and check-in
Females of childbearing potential must agree to utilize protocol recommended highly effective contraception methods from three weeks prior to the single dose of study drug and for 30 days following the single dose of study drug
a. Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least 3 months prior to study dosing
- Males must agree to utilize a protocol recommended highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following last dose of study drug. Periodic abstinence and withdrawal are not acceptable methods of contraception
- Males must refrain from sperm donation from Day -2 through completion of the study and continuing for at least 90 days from the date of last dose of study drug
- Willing and able to comply with the requirements of the protocol and directions from the clinic staff
- Willing to avoid consumption of grapefruit, grapefruit juice and Seville oranges within 2 weeks prior to the single dose of study drug until discharge from the clinic
- Willing to avoid consumption of nicotine (including nicotine gum) and alcoholic beverages within 2 weeks prior to the single dose of study drug until discharge from the clinic
- Understand and willing to sign informed consent
Exclusion Criteria:
- Ongoing or history of any medical or surgical condition that, in the judgment of the Investigator, might jeopardize the individual's safety or interfere with the absorption, distribution, metabolism or excretion of the study drug
- History of meningitis or encephalitis, seizures, migraines, tremors, myoclonic jerks, sleep disorder, anxiety, syncope, head injuries or a family history of seizures
- Any abnormal electrocardiographic (ECG) findings (except QTc > 460 msec) at screening judged to be clinically significant by the investigator
- Any abnormal laboratory value or physical examination finding at screening or check-in that is judged by the investigator as clinically significant
- History of positive serology test for HIV, or hepatitis B or C
- Positive urine drug test for ethanol, barbiturates, cocaine, opiates, or amphetamines at screening or check-in
- Positive urine cotinine test at check-in
- Current treatment with drugs affecting the QT interval
- Current treatment with sodium-channel blockers, eg, flecainide and mexiletine
- Current treatment with strong or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 and 1A2
- Prior treatment with ranolazine within 7 days prior to study drug administration
- Use of systemic prescription medications or over-the-counter (OTC) medication, including multivitamins, and dietary and herbal supplement within 2 weeks or 5 times the terminal half-lives of the medication (whichever is longer) prior to the single dose of study drug, and for the duration of the study
- Use of any experimental or investigational drug or device within 30 days prior to the single dose of study drug or 5 half-lives of the drug, whichever is longer
- Females who are pregnant or lactating
- History of drug or alcohol abuse within 12 months prior to initial dosing of study drug
- Psychosocial or addictive disorders that would interfere with ability to give informed consent or could compromise compliance with the protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Cohort 1
Participants will receive a single 10 mg dose of GS-6615.
|
GS-6615 tablet(s) administered orally
|
EXPERIMENTAL: Cohort 2
Participants will receive a single 20 mg dose of GS-6615.
|
GS-6615 tablet(s) administered orally
|
EXPERIMENTAL: Cohort 3
Participants will receive a single 30 mg dose of GS-6615.
|
GS-6615 tablet(s) administered orally
|
EXPERIMENTAL: Cohort 4
Participants will receive a single 60 mg dose of GS-6615.
|
GS-6615 tablet(s) administered orally
|
EXPERIMENTAL: Cohort 5
Participants will receive single doses of GS-6615 as follows:
If a participant has a QTcF value of ≤ 420 msec on 2 consecutive time points after the 20 mg dose on Day 1, the participant will receive the maintenance dose of 6 mg on Day 2. |
GS-6615 tablet(s) administered orally
|
EXPERIMENTAL: Cohort 6
Participants will receive single doses of GS-6615 as follows:
|
GS-6615 tablet(s) administered orally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in QTc intervals (Fridericia formula)
Time Frame: Baseline through Day 7
|
Changes in QTc intervals (Fridericia formula; QTcF) from the time-matched ECG in the primary lead V5. In case QT cannot be measured in lead V5, lead II will be designated as the primary lead
|
Baseline through Day 7
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events (AEs)
Time Frame: Baseline through Day 22
|
Baseline through Day 22
|
|
Changes in ECHO parameters
Time Frame: Baseline through Day 7
|
ECHO parameters relevant for measurement of diastolic function will be assessed.
|
Baseline through Day 7
|
Area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration of GS-6615
Time Frame: Baseline through Day 12
|
Baseline through Day 12
|
|
Maximum observed plasma concentration (Cmax) of GS-6615
Time Frame: Baseline through Day 12
|
Baseline through Day 12
|
|
Time to maximum observed concentration (Tmax) of GS-6615
Time Frame: Baseline through Day 12
|
Baseline through Day 12
|
|
Changes in ECG parameters
Time Frame: Baseline through Day 12
|
ECG parameters assessed will include PR, RR, QRS, and QT.
|
Baseline through Day 12
|
Changes in QTc interval (Bazett [QTcB])
Time Frame: Baseline through Day 7
|
Changes in QTcB from the time-matched ECG in the primary lead V5. In case QT cannot be measured in lead V5, lead II will be designated as the primary lead
|
Baseline through Day 7
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GS-US-279-0110
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Long QT Syndrome
-
Nantes University HospitalUnknownLong QT Syndrome Type 1 or 2France
-
Herlev and Gentofte HospitalCompletedSudden Cardiac Death | Long Qt Syndrome 1-2Denmark
-
Gilead SciencesCompleted
-
Tel-Aviv Sourasky Medical CenterUnknownLong QT Syndrome Type 3Israel
-
Gilead SciencesTerminatedLong QT Syndrome Type 3United States, Germany, Canada, Netherlands, Italy, France, Israel, United Kingdom
-
Massachusetts General HospitalBoston University; Mayo Clinic; Beth Israel Deaconess Medical Center; The Cleveland... and other collaboratorsTerminatedLong qt Syndrome | Torsade de PointesUnited States
-
University Hospital, MontpellierInstitut National de la Santé Et de la Recherche Médicale, FranceActive, not recruitingPediatric ALL | Long QT Syndrome | Inherited Cardiac Conduction Disorder | Congenital Long Qt SyndromeFrance
-
KU LeuvenAgentschap voor Innovatie door Wetenschap en TechnologieCompleted
-
KU LeuvenAgentschap voor Innovatie door Wetenschap en TechnologieCompleted
-
NorthShore University HealthSystemUnknownEKG-QT ProlongationUnited States
Clinical Trials on GS-6615
-
Gilead SciencesWithdrawnIschemic Heart Disease
-
Gilead SciencesCompletedLong QT SyndromeUnited States, Romania, Moldova, Republic of
-
Gilead SciencesCompletedIschemic Heart DiseaseUnited States
-
Gilead SciencesCompletedLong QT SyndromeUnited States, Romania, New Zealand, Germany
-
Gilead SciencesTerminatedHypertrophic CardiomyopathyAustralia, United States, Netherlands, Israel, Italy, France, Germany, United Kingdom
-
Gilead SciencesTerminatedLong QT Syndrome Type 3United States, Germany, Canada, Netherlands, Italy, France, Israel, United Kingdom
-
Gilead SciencesCompleted
-
Gilead SciencesCompletedVentricular ArrhythmiaNetherlands, Israel, United States, Denmark, Canada, Germany, Czechia, Hungary, Poland
-
Gilead SciencesCompletedLong QT SyndromeUnited States
-
Gilead SciencesRecruitingChronic Hepatitis BTaiwan, New Zealand