Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).

NCT05906732 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: LQT-1213-0061
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Part 1: This is a Phase 1b, randomized, double-blind, crossover, dose escalation, placebo-controlled study to evaluate the effect of oral LQT-1213 on dofetilide-induced QTc prolongation in healthy adult subjects. This is a 2-treatment, 2-period crossover study with approximately up to 28 healthy subjects, with screening procedures within 28 days of enrolment. Part 2: This is a Phase 2a, single-blind, placebo run-in, multiple-dose safety study to evaluate the safety, tolerability, and PK of LQT-1213 in patients diagnosed with LQT2 or LQT3. Up to 12 participants with LQT2 and up to 12 participants with LQT3 will be recruited.

Conditions

Long QT Syndrome

Keywords

LQT-1213; Congenital Long QT Syndrome; LQTS; Serum glucocorticoid regulated kinase-1; SGK-1 inhibitor; Drug induced long QT

Outcome Measures

Primary Outcomes (16)

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  2.0 hours after administration of study treatment on Day 4.

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  2.5 hours after administration of study treatment on Day 4

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  3.0 hours after administration of study treatment on Day 4

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  3.5 hours after administration of study treatment on Day 4

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  4.0 hours after administration of study treatment on Day 4

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  2.0 hours after administration of study treatment on Day 6

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  2.5 hours after administration of study treatment on Day 6

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  3.0 hours after administration of study treatment on Day 6

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  3.5 hours after administration of study treatment on Day 6

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  4.0 hours after administration of study treatment on Day 6

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  2.0 hours after administration of study treatment on Day 8

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  2.5 hours after administration of study treatment on Day 8

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  3.0 hours after administration of study treatment on Day 8

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  3.5 hours after administration of study treatment on Day 8

• Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo

  The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.

  4.0 hours after administration of study treatment on Day 8

• Part 2: Safety and Tolerability of Oral LQT-1213 in Participants With LQT-2 or LQT-3

  The primary outcome is to measure the incidence of treatment emergent adverse events (TEAEs).

  up to day 12

Secondary Outcomes (16)

• Part 1: Pharmacokinetic LQT-1213 AUC0-t

  0 to 24 hours post-dose on Day 8

• Part 1: Pharmacokinetic Dofetilide AUC0-t

  0 to 24 hours post-dose on Day 8

• Part 1: Pharmacokinetic LQT-1213 AUCtau

  Day 4,6, 8

• Part 1: Pharmacokinetic Dofetilide AUCtau

  Day 4,6,8

• Part 1: Pharmacokinetic LQT-1213 Cmax

  Day 4,6,8

Other Outcomes (28)

• Part 2: Time-matched Placebo-corrected QTcF - 1 Hour Post Dose

  1 hour after administration of study treatment on Day 4.

• Part 2: Time-matched Placebo-corrected QTcF at 2 Hours Post-dose

  2 hours after administration of study treatment on Day 4.

• Part 2: Time-matched Placebo-corrected QTcF at 3 Hours Post-dose

  3 hours after administration of study treatment on Day 4.

Study Arms (4)

Part 1: Arm A: Dofetilide with dose-escalating LQT-1213 TID followed by Dofetilide with placebo

EXPERIMENTAL

Sequence A :Dofetilide 500 μg BID (Days 1-8) and LQT-1213 TID 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8. After adequate washout, Dofetilide 500 μg BID (Days 1-8) and placebo (Days 3-8).

Drug: LQT-1213; Drug: Placebo; Drug: Dofetilide 250 μg Cap

Part 1: Arm B: Dofetilide with placebo followed by Dofetilide with LQT-1213 TID

EXPERIMENTAL

Sequence B : Dofetilide 500 μg BID, orally (Days 1-8) and placebo TID (Days 3-8). After adequate washout, Dofetilide 500 μg BID, orally (Days 1-8) and LQT-1213 3 times a day (TID) 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8.

Drug: LQT-1213; Drug: Placebo; Drug: Dofetilide 250 μg Cap

Part 2: TID dosing of LQT-1213 16 mg (48 mg Daily)

EXPERIMENTAL

LQT-1213 16 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.

Drug: LQT-1213; Drug: Placebo

Part 2: TID dosing of LQT-1213 7mg (21 mg Daily)

EXPERIMENTAL

LQT-1213 7 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.

Drug: LQT-1213; Drug: Placebo

Interventions

LQT-1213 DRUG

LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor

Part 1: Arm A: Dofetilide with dose-escalating LQT-1213 TID followed by Dofetilide with placebo; Part 1: Arm B: Dofetilide with placebo followed by Dofetilide with LQT-1213 TID; Part 2: TID dosing of LQT-1213 16 mg (48 mg Daily); Part 2: TID dosing of LQT-1213 7mg (21 mg Daily)

Placebo DRUG

Matching Placebo

Part 1: Arm A: Dofetilide with dose-escalating LQT-1213 TID followed by Dofetilide with placebo; Part 1: Arm B: Dofetilide with placebo followed by Dofetilide with LQT-1213 TID; Part 2: TID dosing of LQT-1213 16 mg (48 mg Daily); Part 2: TID dosing of LQT-1213 7mg (21 mg Daily)

Dofetilide 250 μg Cap DRUG

Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker

Part 1: Arm A: Dofetilide with dose-escalating LQT-1213 TID followed by Dofetilide with placebo; Part 1: Arm B: Dofetilide with placebo followed by Dofetilide with LQT-1213 TID

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part1:
• Male and female subjects between 18 and 60 years of age (inclusive) at Screening.
• Not previously enrolled in a clinical study with LQT-1213.
• Normal general health.
• Body mass index within 18.0 to 32.0 kg/m2, inclusively at Screening.
• Female subjects of nonchildbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone in the postmenopausal range at Screening, based on the central laboratory's ranges.
• Female subjects of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must use a highly effective contraceptive regimen during their participation in the study and for 30 days after the last administration of study drug. Highly effective contraceptive methods are defined as those with \<1% failure rate per year. Acceptable methods of contraception for female subjects enrolled in the study include the following:
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
• Intrauterine device
• Intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Heterosexual abstinence
• Male subjects and their partners must use highly effective methods of contraception (ie, condom and spermicide) for the entire duration of the study. Male subjects must continue to use contraception and refrain from fathering a child and sperm donation for 90 days after the last administration of study drug. Acceptable methods of contraception for male subjects enrolled in the study include the following:

You may not qualify if:

• Part 1:
• On Day 1 at 3 hours postdose in Period 1 only, of the first cycle of dofetilide, the QTcF on the triplicate ECGs will be manually confirmed by cardiologist experienced in ECG interval measurements. The ECG measurements at baseline and at the 3-hour time points will be performed by the same technician and cardiologist. If the mean QTcF increase from baseline is \<25 ms on triplicate safety ECGs compared to the mean from baseline (all ECG QTcF measurements averaged), the subject will be disqualified from further study participation.
• Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition, which, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results. No history of myocardial infarction or angina or ischemic heart disease, nonsustained or sustained ventricular tachycardia, atrial fibrillation, stroke, transient ischemic attack, syncope, congestive heart failure, family history of LQTS, Torsades de Pointes, or sudden cardiac death.
• Female subjects must not be pregnant, lactating, or breastfeeding, and must not be planning to become pregnant.
• Female subjects of childbearing potential must have a negative result for the serum pregnancy test at Screening and Check-in.
• Clinically significant abnormal findings on the physical examination or medical history during Screening as deemed by the investigator.
• Participated in a previous clinical study in the previous 3 months before dosing.
• Donation of blood volume greater than 300 mL within 30 days before Screening and agree to avoid donation from Screening and throughout the study.
• At Screening and on Day -2, if the 12-lead ECG demonstrates any of the following: PR \>240 ms; QRS \>110 ms, or QTcF \<400 ms and \>440 ms; second- or third-degree atrioventricular block; bundle branch block, significant ST-T wave abnormalities or flat T waves that could interfere with QT analysis. If HR \<50 or \>85 bpm, then 2 more ECGs will be recorded, and the mean values will be used.
• Known sensitivity to kinase inhibitors.
• Subject has a positive serology test for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibody at Screening.
• Subject has a history of hypersensitivity to drugs with a clinically significant reaction or any clinically significant hypersensitivities.
• Subject has an allergy to band aids, adhesive dressing, or medical tape.
• Subject is unable to refrain from or anticipates the use of any drug, including prescription and nonprescription medications (with the exception of hormonal contraception), herbal preparations, or vitamin supplements beginning 14 days before the first dose and until the end of the study. After dosing, acetaminophen (up to 2 g per 24 hours) may be administered at the discretion of the investigator or designee.
• Hepatic or renal clearance altering agents within 30 days before the first dose and until the end of the study.

Sponsors & Collaborators

• Thryv Therapeutics, Inc.: lead

Study Sites (1)

Spaulding Clinical Research, LLC

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Conditions

Long QT Syndrome

Interventions

dofetilide; Capsules

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: VP Clinical Research
• Organization: Thryv Therapeutics Inc.

admin@thryvtrx.com

514-973-0915

Study Officials

• Jan Matousek, DO

  Spaulding Clinical Research LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 18, 2023
• Study Start: March 12, 2023
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: July 24, 2025
• Results First Posted: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)