Phase 1 Study of LQT-1213 in Healthy Adults

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Randomized, Double-blinded, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluated the Safety, Tolerability, Pharmacokinetics, Food Effect, and Pharmacodynamics of LQT-1213 in Healthy Adult Participants

Conditions
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Long QT Syndrome

Intervention / Treatment
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* Drug: LQT-1213
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Ascending Dose (SAD) LQT-1213<br>In Part A, 4 dosing cohorts will receive a single oral dose of LQT-1213. The highest dose of LQT-1213 to be administered is 1.67 mg/kg. | Drug: LQT-1213<br>* LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor<br>|
| Experimental: Part A: Food Effect LQT-1213<br>In Part A, food effect will be integrated into one of the SAD cohorts as a single dose, two-period with at least a 7-day washout, crossover cohort. | Drug: LQT-1213<br>* LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor<br>|
| Experimental: Part B: Multiple Ascending Dose (MAD) LQT-1213<br>In Part B, 3 dosing cohorts will receive LQT-1213 in the morning on Day 1 and Day 7 and twice daily (BID) on Days 2 to 6. | Drug: LQT-1213<br>* LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor<br>|
| Placebo Comparator: Part A: Single Ascending Dose (SAD) Placebo<br>In Part A, 6 dosing cohorts will receive a single oral dose of placebo. | Other: Placebo<br>* Matching Placebo<br>|
| Placebo Comparator: Part A: Food Effect Placebo<br>In Part A, food effect will be integrated into one of the SAD cohorts as a single dose, two-period with at least a 7-day washout, crossover cohort. | Other: Placebo<br>* Matching Placebo<br>|
| Placebo Comparator: Part B: Multiple Ascending Dose (MAD) Placebo<br>In Part B, 3 dosing cohorts will receive placebo in the morning on Day 1 and Day 7 and twice daily (BID) on Days 2 to 6. | Other: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability: Number of Participants with Adverse Events | Number of Participants with Adverse Events | Part A SAD: Day 7; Part A Food Effect: Day 15; Part B MAD: Day 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetics of LQT-1213: Tlag | Initial plasma concentration lag time | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8 | 
| Plasma Pharmacokinetics of LQT-1213: Cmax | Maximum observed plasma drug concentration | 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 | 
| Plasma Pharmacokinetics of LQT-1213: Tmax | Time to maximum observed plasma drug concentration | 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 | 
| Plasma Pharmacokinetics of LQT-1213: T1/2 | Terminal phase half-life | 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 | 
| Plasma Pharmacokinetics of LQT-1213: AUC0-12, AUC0-T, and AUC0-∞= | Area under the plasma drug concentration versus time curve | 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 | 
| Plasma Pharmacokinetics of LQT-1213: CL/F | Clearance, parent only | 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 | 
| Plasma Pharmacokinetics of LQT-1213: Vz/F | Volume of distribution, parent only | 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 | 
| Plasma Pharmacokinetics of LQT-1213: λz | Terminal elimination rate constant | Part A SAD: Serially on Day 1; Part A Food Effect: Serially on Day 1 and Day 8 | 
| Urine Pharmacokinetics of LQT-1213: Ae | Amount of the administered dose recovered over the entire 24-hour interval | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | 
| Urine Pharmacokinetics of LQT-1213: Ae0-t | Amount excreted unchanged in urine over a given time interval | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | 
| Urine Pharmacokinetics of LQT-1213: Fe | Percentage of the administered dose recovered over the entire 24-hour interval | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | 
| Urine Pharmacokinetics of LQT-1213: Fe/F | Fraction of dose excreted in urine | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | 
| Urine Pharmacokinetics of LQT-1213: CLR | Renal clearance Ae0-t/AUC0-t | Part A SAD and Food Effect: Serially on Day 1; Part B MAD: Serially on Days 1, 2, 7 and 8 | 
| Plasma Pharmacokinetics of LQT-1213: Ctrough | Concentration of drug in the blood immediately before the next dose is administered | Part B MAD: Days 3-6 | 
| Plasma Pharmacokinetics of LQT-1213: Cmin | Minimum observed plasma drug concentration | Part B MAD: Day 7 | 
| Plasma Pharmacokinetics of LQT-1213: AUC0-tau, AUC0-T, and AUC0-∞ | Area under the plasma drug concentration versus time curve | Part B MAD: Day 7 | 
| Plasma Pharmacokinetics of LQT-1213: CL/Fss | Clearance, parent only | Part B MAD: Day 7 | 
| Plasma Pharmacokinetics of LQT-1213: Vz/Fss | Volume of Distribution, parent only | Part B MAD: Day 7 | 
| Plasma Pharmacokinetics of LQT-1213: Rac(AUC) and Rac(Cmax) | Drug accumulation ratio | Part B MAD: Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LQT-1213, Congenital Long QT Syndrome, LQTS, Serum glucocorticoid regulated kinase-1, SGK-1 inhibitor