Long QT SyndromePhase 1NCT01849003
Study of the Effect of GS-6615 in Subjects With LQT-3
A Phase 1 study testing GS-6615 in people with Long QT Syndrome, run by Gilead Sciences at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Long QT Syndrome
- What is being tested?
- GS-6615
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Rochester Medical Center/Strong Memorial Hospital
Rochester, New York, 14620
About this study
Official title: 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.
- Conditions
- Long QT Syndrome
- Being tested
- GS-6615
- Keywords
- Long QT Syndrome, LQTS, Long QT-3 Syndrome, LQT-3, prolonged QT interval, GS-6615, late sodium current inhibitor
- Medical subject headings
- Long QT Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-6615Drug
GS-6615 tablet(s) administered orally
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants will receive a single 10 mg dose of GS-6615. Receives: Drug: GS-6615 |
| Cohort 2 | Experimental | Participants will receive a single 20 mg dose of GS-6615. Receives: Drug: GS-6615 |
| Cohort 3 | Experimental | Participants will receive a single 30 mg dose of GS-6615. Receives: Drug: GS-6615 |
| Cohort 4 | Experimental | Participants will receive a single 60 mg dose of GS-6615. Receives: Drug: GS-6615 |
| Cohort 5 | Experimental | Participants will receive single doses of GS-6615 as follows:
* Day 1: 20 mg (loading dose)
* Day 2: 40 mg (loading dose)
* Days 3-7: 6 mg (maintenance dose) once daily
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. Receives: Drug: GS-6615 |
| Cohort 6 | Experimental | Participants will receive single doses of GS-6615 as follows:
* Day 1: 50 mg (loading dose)
* Day 2-3: 10 mg once daily
* Days 4-7: 20 mg once daily Receives: Drug: GS-6615 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in QTc intervals (Fridericia formula)
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
- Change from the time-matched ECG on Day -1 to Day 1 for Cohorts 1-4
- Change from the time-matched ECG average of Day -1 and Day -2 to Days 1-7 for Cohort 5 and 6
Measured: Baseline through Day 7
Secondary outcomes (7)
Incidence of Adverse Events (AEs)
Measured: Baseline through Day 22
Changes in ECHO parameters
ECHO parameters relevant for measurement of diastolic function will be assessed.
Measured: Baseline through Day 7
Area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration of GS-6615
Measured: Baseline through Day 12
Maximum observed plasma concentration (Cmax) of GS-6615
Measured: Baseline through Day 12
Time to maximum observed concentration (Tmax) of GS-6615
Measured: Baseline through Day 12
Changes in ECG parameters
ECG parameters assessed will include PR, RR, QRS, and QT.
- PR: electrocardiographic interval occurring between the onset of the P wave and the QRS complex representing time for atrial and ventricular depolarization, respectively
- RR: electrocardiographic interval representing the time measurement between the R wave of one heartbeat and the R wave of the preceding heartbeat
- QRS: electrocardiographic deflection between the beginning of the Q wave and termination of the S wave representing time for ventricular depolarization
- QT: electrocardiographic interval between the beginning of the Q wave and termination of the T wave representing the time for both ventricular depolarization and repolarization to occur
Measured: Baseline through Day 12
Changes in QTc interval (Bazett [QTcB])
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
- Change from the time-matched ECG on Day -1 to Day 1 for Cohorts 1-4
- Change from the time-matched ECG average of Day -1 and Day -2 to Days 1-7 for Cohort 5 and 6
Measured: Baseline through Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study startMay 2013
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long QT SyndromeStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Elizabeth Layug, MD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849003
- Sponsor's protocol ID
- GS-US-279-0110
- Status last verified
- Nov 2014
- First submitted
- 6 May 2013
- Last updated
- 17 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01849003
- Acronym / sponsor ID
- GS-US-279-0110
- Conditions
- Long QT Syndrome
- Keywords
- Long QT Syndrome, LQTS, Long QT-3 Syndrome, LQT-3, prolonged QT interval, GS-6615, late sodium current inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 8 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: GS-6615Participants will receive a single 10 mg dose of GS-6615. |
| Cohort 2 | Experimental | Drug: GS-6615Participants will receive a single 20 mg dose of GS-6615. |
| Cohort 3 | Experimental | Drug: GS-6615Participants will receive a single 30 mg dose of GS-6615. |
| Cohort 4 | Experimental | Drug: GS-6615Participants will receive a single 60 mg dose of GS-6615. |
| Cohort 5 | Experimental | Drug: GS-6615Participants will receive single doses of GS-6615 as follows: * Day 1: 20 mg (loading dose) * Day 2: 40 mg (loading dose) * Days 3-7: 6 mg (maintenance dose) once daily 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. |
| Cohort 6 | Experimental | Drug: GS-6615Participants will receive single doses of GS-6615 as follows: * Day 1: 50 mg (loading dose) * Day 2-3: 10 mg once daily * Days 4-7: 20 mg once daily |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (16 listed)
- 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
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 |
|---|---|---|
| GS-6615GS-6615 tablet(s) administered orally | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
Primary outcome
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 * Change from the time-matched ECG on Day -1 to Day 1 for Cohorts 1-4 * Change from the time-matched ECG average of Day -1 and Day -2 to Days 1-7 for Cohort 5 and 6
7 secondary outcomes
Incidence of Adverse Events (AEs)
Time frame: Baseline through Day 22
Changes in ECHO parameters
Time frame: 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
Maximum observed plasma concentration (Cmax) of GS-6615
Time frame: Baseline through Day 12
Time to maximum observed concentration (Tmax) of GS-6615
Time frame: Baseline through Day 12
Changes in ECG parameters
Time frame: Baseline through Day 12
Changes in QTc interval (Bazett [QTcB])
Time frame: Baseline through Day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2014.
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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.
Elizabeth Layug, MD study director
Gilead Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GS-6615 in people with Long QT Syndrome, run by Gilead Sciences at 1 site in United States.
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 13 inclusion and 16 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 17 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in QTc intervals (Fridericia formula) (time frame: Baseline through Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Nov 2014; AzTrials last refreshed its copy on 8 Nov 2026.