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Long QT SyndromePhase 1/2NCT05906732

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).

A Phase 1/2 study testing LQT-1213 and Dofetilide 250 μg Cap in people with Long QT Syndrome, run by Thryv Therapeutics, Inc. at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Long QT Syndrome
What is being tested?
LQT-1213 and Dofetilide 250 μg Cap
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
42 participants
Where
1 siteUnited States
Study dates
12 Mar 2023to 31 May 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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:
  • Condoms and spermicide
  • Surgical sterilization (vasectomy) of the subject at least 26 weeks before Screening
  • Heterosexual abstinence (subject must agree to use condom and spermicide if they become sexually active)
  • Understand the requirements of the study and voluntarily consent to participate in the study.
  • Part 2:
  • Male and female participants 18 years of age or older at Screening.
  • Body weight of at least 45 kg at Screening.
  • Female participants 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 (>40 mlU/mL) at Screening, based on the central laboratory's ranges.
  • Female participants 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 participants 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 participants and their partners must use highly effective methods of contraception (ie, condom and spermicide) for the entire duration of the study. Male participants 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 participants enrolled in the study include the following:
  • Condoms and spermicide
  • Surgical sterilization (vasectomy) of the participant at least 26 weeks before Screening
  • Heterosexual abstinence (participant must agree to use condom and spermicide if they become sexually active)
  • LQT2 or LQT3 mutation:
  • LQTS 2: Participants with potassium voltage-gated channel subfamily H member 2 (KCNH2) mutations that are dominant negative and considered to be pathologic or likely pathologic by the screening laboratory can be included after approval from the sponsor. Participants with haploinsufficiency will not be eligible for this study.
  • LQTS 3: Participants with a sodium voltage-gated channel alpha subunit 5 (SCN5A) gene chromosome 3 mutations that are mutations and considered to be pathologic or likely pathologic by the screening laboratory can be included after approval from the sponsor. Participants with mutations not associated with Brugada syndrome or overlap syndromes or where mutations affect the window current or the persistent 'late' Na current to exert a primary or major role in the phenotype, will be eligible for this study.
  • QTcF interval ≥480 and ≤560 ms determined at Screening and on Day -1 triplicate ECGs as assessed by a physician trained in complex ECG interpretation.
  • The first 2 participants with LQT2 require having an ICD before further participants with LQT2 are enrolled and the first 2 participants with LQT3 require having an ICD before further participants with LQT3 are enrolled. This stipulation may be altered based on agreement between the principal investigator and Sponsor based on emerging data. The ICD implantation must have been at least 2 months before Screening.
  • Note: Subsequent participants may or may not have had an ICD. The results of the ICD interrogation within the last 6 months should be available for review unless waived by the investigator and sponsor.
  • Understand the requirements of the study and voluntarily consent to participate in the study.

Who cannot join

  • 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.
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  • 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.
  • Abnormal renal function with an estimated glomerular filtration rate (eGFR) of <70 mL/min/1.73 m2, with eGFR calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula at Screening. One retest of the exclusionary eGFR value is allowed at the discretion of the investigator.
  • Subject has abnormal liver function tests (transaminases or total bilirubin) greater than 2.5 × the upper limit of normal at Screening or baseline. One retest of exclusionary abnormal liver function tests is allowed at the discretion of the investigator.
  • Subject has a positive serology test for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibody at Screening.
  • Subject has a hemoglobin <11.0 g/dL, potassium <3.8 mg/dL, magnesium <1.9 mg/dL, or calcium <8.5 mg/dL at Screening or baseline. One retest of exclusionary hemoglobin, potassium, magnesium, and calcium is allowed at the discretion of the investigator. Electrolyte supplementation is allowed at any time as long as it is >4 hours before dosing.
  • 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 has a history within the past 2 months of strenuous exercise (eg, marathon running) and is unwilling to refrain from strenuous exercise from 7 days before Check-in and until the end of the study. Subject has abnormal creatine phosphokinase test greater than 3 × the upper limit of normal at Screening and baseline. One retest of exclusionary abnormal creatine phosphokinase tests is allowed at the discretion of the investigator.
  • 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.
  • Avoid vaccinations from Screening until the end of the study.
  • Has consumed cruciferous vegetables (eg, kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard greens) or charbroiled meats within 7 days before Check-in through the Follow-up Visit.
  • Use of any drugs known to be significant strong inducers of cytochrome P450 (CYP) 3A enzymes, including St. John's Wort, for 28 days before Day -1 or 5 half-lives (whichever is longer) and through the Follow-up Visit.
  • Has consumed Seville oranges, grapefruit and/or grapefruit juice within 14 days before Check-in and is unwilling to abstain from consuming these items until the end of the study.
  • Subject is considering or scheduled to undergo any surgical procedure during the study.
  • Subject has experienced an acute illness that has resolved in less than 14 days before the first study drug dose or has had a major illness or hospitalization within 1 month before the first study drug dose.
  • Subject is unwilling to abstain from ingestion of caffeine- or xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.) beginning 96 hours before Check-in until the final PK sample of the study has been collected.
  • Subject is unwilling to abstain from alcohol beginning 48 hours before Check-in and until the final PK sample of the study has been collected.
  • Subject has a history of high alcohol consumption within 9 months before Screening, defined as an average weekly intake of >14 units for males or >10 units for females.
  • One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine, or 1 measure (25 mL) of spirits.
  • Subject has a history of drug abuse in the 3 years before Screening or positive screen for drugs of abuse or alcohol at Screening or baseline. Subjects may undergo a repeat urine drug screen at the discretion of the investigator.
  • Subject uses or has used tobacco-or nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff, etc.) within 6 months before Screening and is unwilling to abstain from tobacco-containing products until the end of the study, based on subject self-reporting.
  • Subject, who, for any reason, is deemed by the investigator to be inappropriate for this study or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or PK of the investigational drug or prevent compliance with the study protocol.
  • Part 2:
  • Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or significant structural cardiovascular disease or any other condition beyond LQT2 or LQT3, which, in the opinion of the investigator or sponsor, would jeopardize the safety of the participant or impact the validity of the study results. History of myocardial infarction or ongoing angina or active ischemic heart disease, atrial fibrillation, stroke, or transient ischemic attack within the past 12 months, greater than New York Heart Association Class II congestive heart failure, bundle branch block, hemodynamically significant ventricular tachycardia not due to Torsades de Pointes, or Brugada syndrome.
  • Participant has a history of an aborted cardiac arrest, ICD implantation, syncopal episode due to a ventricular arrhythmia or where confidence in the etiology cannot be established, or appropriate ICD therapy for ventricular tachycardia/ventricular fibrillation within 2 months before Screening. Participants with LQT2 or LQT3 can be enrolled after the 2-month time period has lapsed.
  • Female participants must not be pregnant, lactating, or breastfeeding, and must not be planning to become pregnant.
  • Female participants 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 at Check-in or medical history during Screening as deemed by the principal investigator.
  • Currently participating in another interventional clinical study.
  • Donation of blood volume greater than 300 mL within 30 days before dosing and unwilling to avoid donation from Screening and throughout the study.
  • Screening diastolic blood pressure <45 or >95 mm Hg, systolic blood pressure <90 or >150 mm Hg, or with sponsor and investigator approval.
  • At Screening and on Day -1, if the triplicate 12-lead ECG demonstrates any of the following: mean PR >250ms; QRS >110 ms, or QTcF >560 ms and <480 ms; bundle branch block or significant ST-T wave abnormalities or flat T waves that could interfere with QT analysis. Heart rate <45 bpm, unless receiving a beta-blocker in which case <40 bpm, or HR >95 bpm. If any of these exclusionary criteria are met, then a second set of triplicate ECGs may be acquired, and the mean values may be used. For participants on beta blockade, the PR interval may be higher than 250 ms with sponsor and investigator approval.
  • Atrial pacing rate set to ≥80 bpm in those with atrial pacing.
  • Participant has a pacemaker or ICD that is actively used for ventricular pacing.
  • Known sensitivity to kinase inhibitors or clinically significant drug allergies to any of the components of LQT-1213.
  • Abnormal renal function with an eGFR of <60 mL/min/1.73 m2, with eGFR calculated by the CKD-EPI formula at Screening. One retest of the exclusionary eGFR value is allowed at Screening and Check-in at the discretion of the investigator.
  • Participant has abnormal liver function tests (transaminases greater than 2 × the upper limit of normal [ULN] or total bilirubin > 1.5 × ULN. If the participant has documented Gilbert's Syndrome, participation is at the combined principal investigator and Sponsor's discretion after review of historical liver and bilirubin tests.
  • Participant has a positive serology test for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibody at Screening.
  • Participant has a hemoglobin <11.0 g/dL, potassium <3.8 mg/dL, magnesium <1.8 mg/dL, or calcium <8.5 mg/dL at Screening or baseline. One retest of exclusionary hemoglobin, potassium, magnesium, and calcium is allowed at the discretion of the investigator.
  • Participant has a history of hypersensitivity to drugs with a clinically significant reaction or any clinically significant hypersensitivities.
  • Participant has a clinically significant allergy to band aids, adhesive dressing, ECG electrodes, or medical tape.
  • Participant has abnormal creatine phosphokinase test greater than 3 × the ULN at Screening or baseline. One retest of exclusionary abnormal creatine phosphokinase tests is allowed at the discretion of the investigator.
  • Participant is currently taking, within the last 7 days before Spaulding admission or 5 half-lives (whichever is longer), or anticipates the use of any antiarrhythmic medications (including mexilitene except beta-blockers which are allowed,) or drugs known to affect the QT interval (including ranolazine; refer to drug lists for "Drugs with known, possible, or conditional risk of TdP" that are known to prolong the QT interval at https://crediblemeds.org), unless approved by the sponsor and principal investigator.
  • Participant is not permitted to use/consume the following:
  • Any drugs known to be significant strong inducers of CYP 3A enzymes, including St. John's Wort, for 28 days before Day -1 or 5 half-lives (whichever is longer) and through the Follow-up Visit.
  • Seville oranges, grapefruit and/or grapefruit juice within 7 days before Check-in and is unwilling to abstain from consuming these items until the end of the study.
  • Participant is considering or scheduled to undergo any surgical procedure during the study.
  • Participant has experienced an acute illness that has resolved in less than 14 days before the first study drug dose or has had a major illness or hospitalization within 1 month before the first study drug dose.
  • Participant is unwilling to abstain from ingestion of caffeine- or xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.) beginning 96 hours before Check-in until the final PK sample of the study has been collected.
  • Participant is unwilling to abstain from alcohol beginning 48 hours before Check-in and until the final PK sample of the study has been collected.
  • Participant has a history of high alcohol consumption or substance abuse that would pose a risk for the participant's safety and compliance with the study protocol. Participant must not have positive screen for drugs of abuse at Screening or baseline and alcohol at baseline, except with sponsor permission. Participants may undergo a repeat urine drug screen at the discretion of the investigator.
  • Participant, who, for any reason, is deemed by the investigator to be inappropriate for this study or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or PK of the investigational drug or prevent compliance with the study protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Spaulding Clinical Research, LLC

    West Bend, Wisconsin, 53095

Other trials in United States

About this study

Official title: A Phase 1b/2a, 2-Part Study; Part 1: Randomized, Double-Blind, Crossover, Dose-Escalation, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SGK-1 Kinase Inhibition by LQT-1213 on Dofetilide-Induced QTc Prolongation in Healthy Adult Subjects. Part 2: Single-Blind, Multiple-Dose, Safety Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LQT-1213 in Patients Diagnosed With Type 2 or 3 Long QT Syndrome

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.

Read the detailed description

Part 1: This is a 2-treatment, 2-period crossover study. Approximately 28 healthy subjects, with the attempt to balance for sexes, will be enrolled to complete approximately up to 20 subjects in the study. In both treatment periods, all subjects will receive dofetilide on Days 1 and 2 of each period. Randomization will take place before Day 3 of Period 1. Subjects will be randomly assigned to 1 of 2 treatment sequences (AB or BA).

Part 2: Up to 12 participants with LQT2 and up to 12 participants with LQT3 will be enrolled. After initial screening, which may be conducted remotely by the CRU, individual participants with LQT2 or LQT3 will undergo a 1-day, single-blind placebo run-in period followed by 3 dosing days of LQT-1213 administered TID (the last dosing day will have a single dose). Participants will be discharged from the CRU on Day 5. Approximately 7 days after discharge from the CRU, the Follow-up Visit will be conducted remotely via telephone call.

Being tested
LQT-1213, Placebo, Dofetilide 250 μg Cap
Keywords
LQT-1213, Congenital Long QT Syndrome, LQTS, Serum glucocorticoid regulated kinase-1, SGK-1 inhibitor, Drug induced long QT
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.

  • LQT-1213Drug

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

  • PlaceboDrug

    Matching Placebo

  • Dofetilide 250 μg CapDrug

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

Study groups in NCT05906732
Study groupRoleWhat they receive
Part 1: Arm A: Dofetilide with dose-escalating LQT-1213 TID followed by Dofetilide with placeboExperimentalSequence 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).
Receives: Drug: LQT-1213; Drug: Placebo; Drug: Dofetilide 250 μg Cap
Part 1: Arm B: Dofetilide with placebo followed by Dofetilide with LQT-1213 TIDExperimentalSequence 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.
Receives: Drug: LQT-1213; Drug: Placebo; Drug: Dofetilide 250 μg Cap
Part 2: TID dosing of LQT-1213 16 mg (48 mg Daily)ExperimentalLQT-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.
Receives: Drug: LQT-1213; Drug: Placebo
Part 2: TID dosing of LQT-1213 7mg (21 mg Daily)ExperimentalLQT-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.
Receives: Drug: LQT-1213; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2.0 hours after administration of study treatment on Day 4.

  2. 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.

    Measured: 2.5 hours after administration of study treatment on Day 4

  3. 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.

    Measured: 3.0 hours after administration of study treatment on Day 4

  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.

    Measured: 3.5 hours after administration of study treatment on Day 4

  5. 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.

    Measured: 4.0 hours after administration of study treatment on Day 4

  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.

    Measured: 2.0 hours after administration of study treatment on Day 6

  7. 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.

    Measured: 2.5 hours after administration of study treatment on Day 6

  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.

    Measured: 3.0 hours after administration of study treatment on Day 6

  9. 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.

    Measured: 3.5 hours after administration of study treatment on Day 6

  10. 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.

    Measured: 4.0 hours after administration of study treatment on Day 6

  11. 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.

    Measured: 2.0 hours after administration of study treatment on Day 8

  12. 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.

    Measured: 2.5 hours after administration of study treatment on Day 8

  13. 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.

    Measured: 3.0 hours after administration of study treatment on Day 8

  14. 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.

    Measured: 3.5 hours after administration of study treatment on Day 8

  15. 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.

    Measured: 4.0 hours after administration of study treatment on Day 8

  16. 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).

    Measured: up to day 12

Secondary outcomes (16)

  1. Part 1: Pharmacokinetic LQT-1213 AUC0-t

    Area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration

    Measured: 0 to 24 hours post-dose on Day 8

  2. Part 1: Pharmacokinetic Dofetilide AUC0-t

    Area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration

    Measured: 0 to 24 hours post-dose on Day 8

  3. Part 1: Pharmacokinetic LQT-1213 AUCtau

    AUCtau = Area under the curve from time 0 to 8.0 hours

    Measured: Day 4,6, 8

  4. Part 1: Pharmacokinetic Dofetilide AUCtau

    AUCtau = Area under the curve from time 0 to 12 hours

    Measured: Day 4,6,8

  5. Part 1: Pharmacokinetic LQT-1213 Cmax

    Maximum observed plasma drug concentration

    Measured: Day 4,6,8

  6. Part 1: Pharmacokinetic Dofetilide Cmax

    Maximum observed plasma drug concentration

    Measured: Day 4,6, 8

  7. Part 1: Pharmacokinetic LQT-1213 Tmax

    Time to the maximum observed plasma concentration

    Measured: Day 4,6,8

  8. Part 1: Pharmacokinetic Dofetilide Tmax

    Time to the maximum observed plasma concentration

    Measured: Day 4,6,8

  9. Part 1: Pharmacokinetic LQT-1213 t1/2

    Terminal half-life

    Measured: Day 8

  10. Part 1: Pharmacokinetic Dofetilide t1/2

    Terminal half-life

    Measured: Day 8

  11. Part 1: Number of Treatment Emerging Adverse Events (TEAEs)

    Part 1: Number of Treatment Emerging Adverse Events (TEAEs) that occurred following administration of dofetilide Day1 up to Day 10 period 1 and in period 2 from Day 1 to up to the follow-up visit at Day 17.

    Measured: Period 1 from Day 1 to Day 10 and Period 2 from Day 1 up to Day 17.

  12. Part 2: Pharmacokinetic LQT-1213 AUC0-t

    Area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration

    Measured: Day 4 Pre-dose up to 29 hours post-dose administration

  13. Part 2: Pharmacokinetic LQT-1213 AUCtau

    Pharmacokinetic LQT-1213 AUCtau (time 0 to 8 hours)

    Measured: day 2 and day 4

  14. Part 2: Pharmacokinetic LQT-1213 Cmax

    Maximum observed plasma drug concentration

    Measured: day 2 and day 4

  15. Part 2: Pharmacokinetic LQT-1213 Tmax

    Time to the maximum observed plasma concentration

    Measured: Day 2 and Day 4

  16. Part 2: Pharmacokinetic LQT-1213 t1/2

    Part 2: Pharmacokinetic LQT-1213 terminal half-life t1/2

    Measured: Day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2023
  2. Study start12 Mar 2023
  3. Primary completion31 May 2024
  4. Study completion31 May 2024

Why it stopped: Advancing an alternative SGK1 inhibitor.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05906732
Sponsor's protocol ID
LQT-1213-0061
Status last verified
Jul 2025
First submitted
7 Jun 2023
Last updated
24 Jul 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LQT-1213 and Dofetilide 250 μg Cap in people with Long QT Syndrome, run by Thryv Therapeutics, Inc. 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 42 inclusion and 62 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: stopped early, as of the sponsor's last update on 24 Jul 2025. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo (time frame: 2.0 hours after administration of study treatment on Day 4.). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05906732.

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 24 Jul 2025.

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