Long QT Syndrome
Conditions
Keywords
LQT-1213, Congenital Long QT Syndrome, LQTS, Serum glucocorticoid regulated kinase-1, SGK-1 inhibitor
Brief summary
This is a single-center, randomized, double-blind, placebo-controlled study to be conducted in 2 parts: single ascending dose (SAD) incorporating a food effect arm and multiple ascending dose (MAD). Potential participants for each part will undergo screening procedures within 28 days of enrollment.
Interventions
DRUGLQT-1213
LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
OTHERPlacebo
Matching Placebo
Sponsors
Thryv Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy adult male or female participants * Females of childbearing potential must agree and commit to use an adequate form of contraception. * Men who are biologically capable of fathering children must agree and commit to use an adequate form of contraception. * Aged at least 18 years but not older than 60 years (inclusive) * Body mass index (BMI) within 18.0 kg/m\^2 to 32.0 kg/m\^2, inclusively. * Non- or ex-smoker * Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG, as determined by an investigator.
Exclusion criteria
* Clinically significant diseases or any other condition, which, in the opinion of the Investigator, would jeopardize the safety of the participant or impact the validity of the study results. * Clinically significant abnormal findings on the physical examination or medical history during screening as deemed by the principal investigator * Female who is lactating * Female who is pregnant * Male participants with a history of oligospermia or azoospermia or any other disorder of the reproductive system * Male participants who are undergoing treatment or evaluation for infertility. * History of significant hypersensitivity to LQT-1213, kinase inhibitors or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs * Use of immunosuppressant in the 28 days prior to the first study drug administration * Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) * Intake of an investigational product or participation in a clinical trial in the 90 days prior to the first study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability: Number of Participants with Adverse Events | Part A SAD: Day 7; Part A Food Effect: Day 15; Part B MAD: Day 16 | Number of Participants with Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Pharmacokinetics of LQT-1213: Cmax | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8; Part B MAD: Serially on Day 1 and 7 | Maximum observed plasma drug concentration |
| Plasma Pharmacokinetics of LQT-1213: Tmax | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8; Part B MAD: Serially on Day 1 | Time to maximum observed plasma drug concentration |
| Plasma Pharmacokinetics of LQT-1213: T1/2 | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8; Part B MAD: Serially on Day 1 and 7 | Terminal phase half-life |
| Plasma Pharmacokinetics of LQT-1213: AUC0-12, AUC0-T, and AUC0-∞= | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8; Part B MAD: Serially on Day 1 | Area under the plasma drug concentration versus time curve |
| Plasma Pharmacokinetics of LQT-1213: CL/F | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8; Part B MAD: Serially on Day 1 | Clearance, parent only |
| Plasma Pharmacokinetics of LQT-1213: Vz/F | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8; Part B MAD: Serially on Day 1 | Volume of distribution, parent only |
| Plasma Pharmacokinetics of LQT-1213: λz | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8 | Terminal elimination rate constant |
| Urine Pharmacokinetics of LQT-1213: Ae | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | Amount of the administered dose recovered over the entire 24-hour interval |
| Urine Pharmacokinetics of LQT-1213: Ae0-t | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | Amount excreted unchanged in urine over a given time interval |
| Plasma Pharmacokinetics of LQT-1213: Tlag | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8 | Initial plasma concentration lag time |
| Urine Pharmacokinetics of LQT-1213: Fe/F | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | Fraction of dose excreted in urine |
| Urine Pharmacokinetics of LQT-1213: CLR | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | Renal clearance Ae0-t/AUC0-t |
| Plasma Pharmacokinetics of LQT-1213: Ctrough | Part B MAD: Days 3-6 | Concentration of drug in the blood immediately before the next dose is administered |
| Plasma Pharmacokinetics of LQT-1213: Cmin | Part B MAD: Day 7 | Minimum observed plasma drug concentration |
| Plasma Pharmacokinetics of LQT-1213: AUC0-tau, AUC0-T, and AUC0-∞ | Part B MAD: Day 7 | Area under the plasma drug concentration versus time curve |
| Plasma Pharmacokinetics of LQT-1213: CL/Fss | Part B MAD: Day 7 | Clearance, parent only |
| Plasma Pharmacokinetics of LQT-1213: Vz/Fss | Part B MAD: Day 7 | Volume of Distribution, parent only |
| Plasma Pharmacokinetics of LQT-1213: Rac(AUC) and Rac(Cmax) | Part B MAD: Day 7 | Drug accumulation ratio |
| Urine Pharmacokinetics of LQT-1213: Fe | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | Percentage of the administered dose recovered over the entire 24-hour interval |
Countries
United States
Outcome results
None listed