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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: Single Ascending Dose (SAD) LQT-1213 | Experimental | 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. |
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| Part A: Food Effect LQT-1213 | Experimental | 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. |
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| Part B: Multiple Ascending Dose (MAD) LQT-1213 | Experimental | 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. |
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| Part A: Single Ascending Dose (SAD) Placebo | Placebo Comparator | In Part A, 6 dosing cohorts will receive a single oral dose of placebo. |
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| Part A: Food Effect Placebo | Placebo Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LQT-1213 | Drug | LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor |
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| 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 |
| 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 |
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Key Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Altasciences Clinical Los Angeles, Inc. | Cypress | California | 90630 | United States |
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| ID | Term |
|---|---|
| D008133 | Long QT Syndrome |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D000075224 | Cardiac Conduction System Disease |
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| Part B: Multiple Ascending Dose (MAD) Placebo | Placebo Comparator | 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. |
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| Placebo | Other | Matching Placebo |
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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 |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |