28 Participants Needed

LQT-1213 for Long QT Syndrome

DW
Overseen ByDoug Wight
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial tests a new medication, LQT-1213, to help with heart rhythm problems. It involves healthy adults and patients with specific heart rhythm disorders (LQT2 or LQT3). The medication aims to keep the heart's electrical signals normal, preventing irregular heartbeats.

Do I have to stop taking my current medications for the trial?

Yes, participants must stop taking certain medications. For Part 1, you must refrain from using any drugs, including prescription and nonprescription medications, herbal remedies, or vitamin supplements, starting 14 days before the first dose and until the end of the study. For Part 2, you cannot take antiarrhythmic medications or drugs known to affect the QT interval within 7 days before admission or 5 half-lives (whichever is longer), unless approved by the sponsor and principal investigator.

Will I have to stop taking my current medications?

The trial requires participants to refrain from using any prescription or nonprescription medications, herbal remedies, or vitamin supplements starting 14 days before the first dose and until the end of the study, unless approved by the sponsor and principal investigator. This means you may need to stop taking your current medications, but you should discuss this with the study team.

What data supports the idea that LQT-1213 for Long QT Syndrome is an effective drug?

The available research does not provide specific data on the effectiveness of LQT-1213 for Long QT Syndrome. Instead, it discusses other treatments and approaches for managing the condition. For example, one study focuses on the drug flecainide for a specific type of Long QT Syndrome, while another explores a different compound, NS1643, in rabbit models. Additionally, there is mention of personalized care and the use of automated external defibrillators as part of a comprehensive treatment program. However, none of these studies directly address LQT-1213.12345

What safety data is available for the treatment LQT-1213 for Long QT Syndrome?

The provided research does not contain specific safety data for LQT-1213 or its other names like Dofetilide or Tikosyn. The studies focus on other treatments and aspects of Long QT Syndrome, such as flecainide, sevoflurane, and 4-phenylbutyric acid, but do not mention LQT-1213. Therefore, no safety data for LQT-1213 is available in the provided research.14678

Is the drug LQT-1213 a promising treatment for Long QT Syndrome?

The information provided does not directly mention LQT-1213, so we cannot determine if it is a promising treatment for Long QT Syndrome based on the given research articles.124910

How is the drug LQT-1213 different from other treatments for Long QT Syndrome?

LQT-1213 is unique because it may target specific ion channels involved in Long QT Syndrome, potentially offering a more tailored approach compared to existing treatments that often use a 'one-size-fits-all' strategy. This drug could provide a novel mechanism of action by modulating specific pathways related to the condition, unlike traditional treatments that may not address the underlying genetic factors.124910

Research Team

JM

Jan Matousek, DO

Principal Investigator

Spaulding Clinical Research LLC

Eligibility Criteria

Healthy adults and patients with Type 2 or 3 Long QT Syndrome (LQT2 or LQT3) can join this trial. Healthy participants must be 19-60 years old, have a BMI of 18-35 kg/m^2, not have used tobacco recently, and agree to use effective contraception. Patients with LQT need an ICD implanted and a specific QTcF interval. People with certain health conditions, recent blood donations, drug abuse history, or those on conflicting medications cannot participate.

Inclusion Criteria

I understand the study's requirements and agree to participate.
I am a woman who cannot have children because I am either surgically sterile or postmenopausal.
Not previously enrolled in a clinical study with LQT-1213
See 5 more

Exclusion Criteria

Known sensitivity to kinase inhibitors
My liver tests are not normal.
Allergy to band aids, adhesive dressing, or medical tape
See 28 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks
Remote screening

Treatment Part 1

Randomized, double-blind, crossover, dose-escalation study with dofetilide and LQT-1213 in healthy subjects

8 days
Daily visits for dosing and monitoring

Treatment Part 2

Single-blind, multiple-dose safety study of LQT-1213 in patients with Long QT Syndrome

5 days
In-person visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days
Remote follow-up via telephone

Treatment Details

Interventions

  • Dofetilide
  • LQT-1213
  • Placebo
Trial OverviewThe study tests the effects of LQT-1213 on heart rhythm prolongation caused by Dofetilide in healthy subjects (Part1), followed by its safety in patients with congenital Long QT syndrome types LQT2 or LQT3 (Part2). Part1 is a crossover study where subjects receive both treatments at different times; Part2 involves multiple doses for safety evaluation.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Part 2: TID dosing of PlaceboExperimental Treatment1 Intervention
Placebo matched to LQT-1213 (Day 1)TID
Group II: Part 2: TID dosing of LQT-1213Experimental Treatment1 Intervention
LQT-1213 2.24 mg/kg/day TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4 at time 0, though these time points may be adjusted based upon emerging data.
Group III: Part 1: Arm A: 500 μg of Dofetilide BID in combination with dose-escalating LQT-1213 TID, orallyExperimental Treatment2 Interventions
Dofetilide 500 μg BID (2 × 250 μg capsules), orally (Days 1-8) and LQT-1213 3 times a day (TID) low dose (Days 3 and 4), mid dose (Days 5 and 6), and high dose (not to exceed 0.747 mg/kg TID, daily dose 2.24 mg/kg/day) on Days 7 and 8. The specific doses will be determined before administration of the first dose of LQT-1213, but the high dose will not exceed 0.747 mg/kg TID or 2.24 mg/kg/day. Only 1 dose of dofetilide and LQT-1213 will be administered on Day 8.
Group IV: Part 1: Arm B: 500 μg of Dofetilide BID in combination with placeboPlacebo Group2 Interventions
Dofetilide 500 μg BID (2 × 250 μg capsules), orally (Days 1-8) and placebo matched to LQT-1213 TID (Days 3-8). Only 1 dose of dofetilide and placebo matched to LQT-1213 will be administered on Day 8.

LQT-1213 is already approved in United States for the following indications:

🇺🇸
Approved in United States as LQT-1213 for:
  • Congenital Long QT Syndrome (Type 1, 2, and 3)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Thryv Therapeutics, Inc.

Lead Sponsor

Trials
3
Recruited
150+

Findings from Research

Chronic low-dose flecainide therapy significantly reduced the QTc interval in six male LQT-3 patients with the DeltaKPQ deletion, achieving an average reduction of -27.1 ms compared to placebo, indicating its efficacy in this genetic disorder.
The study found minimal prolongation in QRS duration and no major adverse cardiac effects, suggesting that flecainide is safe for use in this small patient group, although the limited sample size means further research is needed to fully assess its safety.
Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial.Moss, AJ., Windle, JR., Hall, WJ., et al.[2020]
Long QT Syndrome (LQTS) is a serious inherited heart condition that can be effectively treated, but management must be personalized based on individual and genetic factors.
The authors emphasize the need to move away from a 'one-size-fits-all' approach to treatment, advocating for tailored strategies that consider the specific genotype of each patient to improve care outcomes.
Personalized Care in Long QT Syndrome: Better Management, More Sports, and Fewer Devices.MacIntyre, CJ., Ackerman, MJ.[2023]
The novel compound NS1643 effectively activates the rapid delayed-rectifier K+ current (I(Kr)), significantly reducing QT interval prolongation and suppressing arrhythmic activity in two rabbit models of long QT syndrome (LQTS).
In both models, NS1643 not only reversed the effects of I(Kr) inhibition but also increased I(Kr) in cardiac myocytes, suggesting that pharmacological activation of I(Kr) could be a promising new treatment strategy for LQTS.
Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome.Diness, TG., Yeh, YH., Qi, XY., et al.[2019]

References

Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): a randomized, double-blind, placebo-controlled clinical trial. [2020]
Personalized Care in Long QT Syndrome: Better Management, More Sports, and Fewer Devices. [2023]
Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome. [2019]
4-phenylbutyric acid re-trafficking hERG/G572R channel protein by modulating the endoplasmic reticulum stress-associated chaperones and endoplasmic reticulum-associated degradation gene. [2023]
Automated external defibrillator rescues among children with diagnosed and treated long QT syndrome. [2018]
Familial and acquired long qt syndrome and the cardiac rapid delayed rectifier potassium current. [2022]
SEVOFLURANE AS A CAUSE OF TORSADE DE POINTES IN PATIENT WITH THE LONG QT SYNDROME: Case Report. [2018]
Precision therapy in congenital long QT syndrome. [2022]
Modulation of Kv 11.1 (hERG) channels by 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), a novel small molecule activator. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
SGK1 inhibition attenuated the action potential duration in patient- and genotype-specific re-engineered heart cells with congenital long QT syndrome. [2023]