Phase 1 Study of LQT-1213 in Healthy Adults

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

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.

Study Overview

• Status: Completed
• Conditions: Long QT Syndrome
• Intervention / Treatment: Other: Placebo; Drug: LQT-1213

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • Altasciences Clinical Los Angeles, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Single Ascending Dose (SAD) LQT-1213; 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; LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Experimental: Part A: Food Effect LQT-1213; 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; LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Experimental: Part B: Multiple Ascending Dose (MAD) LQT-1213; 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; LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo Comparator: Part A: Single Ascending Dose (SAD) Placebo; In Part A, 6 dosing cohorts will receive a single oral dose of placebo.	Other: Placebo; Matching Placebo
Placebo Comparator: Part A: Food Effect Placebo; 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; Matching Placebo
Placebo Comparator: Part B: Multiple Ascending Dose (MAD) Placebo; 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; Matching Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Thryv Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Actual): March 5, 2023
• Study Completion (Actual): March 5, 2023

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: LQTS; Congenital Long QT Syndrome; LQT-1213; Serum glucocorticoid regulated kinase-1; SGK-1 inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Long QT Syndrome
• Other Study ID Numbers: LQT-1213-0059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No