Trial record 8 of 23 for:    "Romano-Ward syndrome" OR "Long QT Syndrome"

Study of the Effect of GS-6615 in Subjects With LQT-3

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01849003
First received: May 6, 2013
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

The purpose of 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 five cohorts of participants in a sequential manner, four single-dose cohorts followed by one multiple-dose cohort.


Condition Intervention Phase
Long QT Syndrome
Drug: GS-6615
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Changes in QTc intervals (Fridericia formula) [ Time Frame: Baseline through Day 7 ] [ Designated as safety issue: No ]

    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


Secondary Outcome Measures:
  • Incidence of Adverse Events (AEs) [ Time Frame: Baseline through Day 22 ] [ Designated as safety issue: No ]
  • Changes in ECHO parameters [ Time Frame: Baseline through Day 7 ] [ Designated as safety issue: No ]
    ECHO parameters relevant for measurement of diastolic function will be assessed.

  • 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 ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) of GS-6615 [ Time Frame: Baseline through Day 12 ] [ Designated as safety issue: No ]
  • Time to maximum observed concentration (Tmax) of GS-6615 [ Time Frame: Baseline through Day 12 ] [ Designated as safety issue: No ]
  • Changes in ECG parameters [ Time Frame: Baseline through Day 12 ] [ Designated as safety issue: No ]
    ECG parameters assessed will include PR, RR, QRS, QT and QTc interval (Bazett [QTcB] and QTcF).

  • Changes in QTcB intervals [ Time Frame: Baseline through Day 7 ] [ Designated as safety issue: No ]

    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


Estimated Enrollment: 25
Study Start Date: May 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Participants will received a single 10 mg dose of GS-6615.
Drug: GS-6615
GS-6615 tablet(s) (1, 3, and 10 mg) administered orally once daily
Experimental: Cohort 2
Participants will received a single 20 mg dose of GS-6615.
Drug: GS-6615
GS-6615 tablet(s) (1, 3, and 10 mg) administered orally once daily
Experimental: Cohort 3
Participants will received a single 30 mg dose of GS-6615.
Drug: GS-6615
GS-6615 tablet(s) (1, 3, and 10 mg) administered orally once daily
Experimental: Cohort 4
Participants will received a single 60 mg dose of GS-6615.
Drug: GS-6615
GS-6615 tablet(s) (1, 3, and 10 mg) administered orally once daily
Experimental: Cohort 5

Multiple-dose cohort: Participants will received single doses of GS-6615:

  • Day 1: 20 mg
  • Day 2: 40 mg
  • Days 3-7: 6 mg (maintenance dose)

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.

Drug: GS-6615
GS-6615 tablet(s) (1, 3, and 10 mg) administered orally once daily

Detailed Description:

Participants in the single-dose cohorts (Cohorts 1-4) will be admitted 2 days prior to study drug administration (Day -2), and remain in clinic for predose assessments on Day -1, study drug administration on Day 1, postdose assessments for 3 days (Days 2-4), and be discharged on Day 4.

Participants in the multiple-dose cohort (Cohort 5) will be admitted 3 days prior to study drug administration (Day -3), and remain in clinic for predose assessments on Day -2 and Day -1, study drug administration from Day 1 through Day 7, postdose assessments for 5 days (Days 8-12) and be discharged on Day 12.

Follow-up contact to assess adverse events (AEs) and concomitant medications will be performed 3 and 10 days after discharge on the following days:

  • Cohorts 1-4 follow-up will occur on Day 7 (+2 days) and Day 14 (+2 days).
  • Cohort 5 follow-up will occur on Day 15 (+2 days) and Day 22 (+2 days).

Subjects 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 AEs and concomitant medications will continue throughout the duration of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects between ages 18-65 years (inclusive) at time of Screening
  2. Documented LQT-3 genotype with one of the following mutations: delta KPQ, R1623Q, N1325S, E1784K or S1787N
  3. QTc > 480 msec in lead V5 at Screening
  4. Weight of at least 50 kg with body mass index (BMI) between 18 and 30 kg/m2 (inclusive)
  5. Females of childbearing potential must have a negative serum pregnancy test at Screening and Check-in
  6. 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. Female subjects 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

  7. Male subjects 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
  8. Male subjects 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
  9. Willing and able to comply with the requirements of the protocol and directions from the clinic staff
  10. 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
  11. 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
  12. Understand and willing to sign informed consent

Exclusion Criteria:

  1. Ongoing or history of any medical or surgical condition that, in the judgment of the Investigator, might jeopardize the subject's safety or interfere with the absorption, distribution, metabolism or excretion of the study drug
  2. History of meningitis or encephalitis, seizures, migraines, tremors, myoclonic jerks, sleep disorder, anxiety, syncope, head injuries or a family history of seizures
  3. Any abnormal electrocardiographic (ECG) findings (except QTc >460 msec) at Screening judged to be clinically significant by the Investigator
  4. Any abnormal laboratory value or physical examination finding at Screening or Check-in that is judged by the Investigator as clinically significant
  5. History of positive serology test for HIV, or hepatitis B or C
  6. Positive urine drug test for ethanol, barbiturates, cocaine, opiates, or amphetamines at Screening or Check-in
  7. Positive urine cotinine test at Check-in
  8. Current treatment with drugs affecting the QT interval
  9. Current treatment with sodium-channel blockers, eg, flecainide and mexiletine
  10. Current treatment with strong or moderate inhibitors or inducers of cytochrome P450 (CYP)3A4 and 1A2
  11. Prior treatment with ranolazine within 7 days prior to study drug administration
  12. 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
  13. 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
  14. Female subjects who are pregnant or lactating
  15. History of drug or alcohol abuse within 12 months prior to initial dosing of study drug
  16. Psychosocial or addictive disorders that would interfere with subject's ability to give informed consent or could compromise compliance with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849003

Locations
United States, New York
University of Rochester Medical Center/Strong Memorial Hospital
Rochester, New York, United States, 14620
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Elizabeth Layug, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01849003     History of Changes
Other Study ID Numbers: GS-US-279-0110
Study First Received: May 6, 2013
Last Updated: June 6, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Long QT Syndrome
LQTS
Long QT-3 Syndrome
LQT-3
prolonged QT interval
GS-6615
late sodium current inhibitor

Additional relevant MeSH terms:
Long QT Syndrome
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities
Pathologic Processes

ClinicalTrials.gov processed this record on July 20, 2014