Study to Assess the Safety, Tolerability, Pharmacokinetic of Thrv-1268

NCT06507839 | Completed Phase 1

• 1 other identifier: 0269
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Atrial Fibrillation

Keywords

THRV-1268; Atrial Fibrillation; Serum glucocorticoid regulated kinase-1; SGK-1 inhibitor

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability: Number of Participants with Adverse Events

  Number of Participants with Adverse Events

  SAD: Day 7; Food Effect: Day 15; MAD: Day 16

Secondary Outcomes (10)

• Pharmacokinetic LQT-1268 AUC0-t

  SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7

• Pharmacokinetic LQT-1268 Cmax

  SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7

• Pharmacokinetic LQT-1268 Tmax

  SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7

• Pharmacokinetic LQT-1268 t1/2

  SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7

• Urine Pharmacokinetics of LQT-1268: Ae

  SAD: Day 1; MAD: Serially on Day 1 and 7

Study Arms (6)

Single Ascending Dose (SAD) THRV-1268

EXPERIMENTAL

5 dosing cohorts will receive a single oral dose of THRV-1268. The highest dose of THRV-1268 to be administered is 500 mg.

Drug: THRV-1268

Food Effect THRV-1268

EXPERIMENTAL

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: THRV-1268

Multiple Ascending Dose (MAD) THRV-1268

EXPERIMENTAL

3 dosing cohorts will receive THRV-1268 in the morning on Day 1 to Day 7.

Drug: THRV-1268

Single Ascending Dose (SAD) Placebo

PLACEBO COMPARATOR

5 dosing cohorts will receive a single oral dose of placebo.

Other: Placebo

Food Effect Placebo

PLACEBO COMPARATOR

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

Multiple Ascending Dose (MAD) Placebo

PLACEBO COMPARATOR

3 dosing cohorts will receive placebo in the morning from Day 1 to Day 7.

Other: Placebo

Interventions

THRV-1268 DRUG

THRV-1268 a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor

Food Effect THRV-1268; Multiple Ascending Dose (MAD) THRV-1268; Single Ascending Dose (SAD) THRV-1268

Placebo OTHER

Matching placebo

Food Effect Placebo; Multiple Ascending Dose (MAD) Placebo; Single Ascending Dose (SAD) Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated Informed Consent Form (ICF). 2.Stated willingness to comply with all study procedures and availability for the duration of the study.
• Healthy adult male or female subjects. 4.If female, meets one of the following criteria:
• Women of childbearing potential who agrees to use any of the acceptable contraceptive methods:
• Abstinence from heterosexual intercourse from Screening through at least 30 days from last study dose.
• One of the following highly-effective contraception methods:
• systemic contraceptives (combined birth control pills, injectable/implant/ insertable hormonal birth control products, or transdermal patch) used from at least 28 days prior to Screening through to at least 30 days from last study dose
• intrauterine device (with or without hormones) used from at least 28 days prior to Screening through to at least 30 days from last study dose
• male partner vasectomized at least 6 months prior to Screening visit
• One of the following double-barrier contraception methods used from Screening through at least 30 days from last study dose
• Male condom used simultaneously with diaphragm plus spermicide
• Male condom used simultaneously with cervical cap plus spermicide Or
• Surgically sterile, defined as those who have had hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy, or bilateral tubal ligation.
• Men who are biologically capable of fathering children must agree and commit to use an adequate form of contraception (see female criteria 3) for the duration of the treatment period and for no less than 90 days after the last study dose. A male subject is considered capable of fathering children even if his sexual partner is sterile or using contraceptives.
• Men who are biologically capable of fathering children must also agree to refrain from sperm donation for the duration of the treatment period and for at least 90 days after the last study dose.
• Aged at least 18 years but not older than 60 years (inclusive). 8.Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively. 9.Non- or ex-smoker (An ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration).

You may not qualify if:

• 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.
• Clinically significant abnormal findings on the physical examination or medical history during Screening as deemed by the Investigator.
• Female who is lactating.
• Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration.
• Male subjects with a history of oligospermia or azoospermia or any other disorder of the reproductive system.
• Male subjects who are undergoing treatment or evaluation for infertility.
• The average of 3 measurements performed approximately 5 min apart: Screening or baseline (Day -1) diastolic BP \<50 mmHg or \>95; systolic BP \<100 mmHg or \>145 mmHg; or HR ≤ 50 beats per minute (bpm) using a validated digital BP device. These can be repeated in triplicate once after an additional quiet resting period.
• Orthostatic BP performed after sitting quietly for at least 4 minutes and then standing for 2 minutes with a duplicate set performed after at least 3 minutes of sitting, with a reduction in systolic BP \>20 mmHg, a reduction in diastolic BP \>10 mmHg, or an increase in HR \>20 bpm using a validated digital BP device.
• Estimated creatinine clearance \< 80 mL/min at Screening.
• History of significant hypersensitivity to THRV-1268, kinase inhibitors or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Screening 12-lead ECG demonstrating at least one of the following: PR \>220 ms; QRS \>110 ms, or QTcF \>440 ms; atrioventricular block; branch bundle block, significant ST-T wave abnormalities or flat T waves that could interfere with QT analysis. Heart rate ≤50 bpm or \>100 bpm.
• History or evidence of any of the following: myocardial infarction; cardiac valvulopathy; cardiac surgery revascularization (coronary artery bypass grafting or percutaneous, transluminal coronary angioplasty); unstable angina; cerebrovascular accident, stroke, or transient ischemic attack; pacemaker; AF, flutter, or nonsustained or sustained ventricular tachycardia; orthostatic hypotension or orthostatic dizziness or lightheadedness, pulmonary arterial hypertension; sick sinus syndrome, second- or third-degree atrioventricular block; uncontrolled hypertension; congestive heart failure; personal or family history of sudden death or long QT syndrome; unexplained syncope or syncope within the last 3 years regardless of etiology.
• Immunization with a Coronavirus Disease (COVID-19) vaccine in the 14 days prior to the first study drug administration.
• Scheduled immunization with a COVID-19 vaccine during the study that, in the opinion of an Investigator, could potentially interfere with subject participation, subject safety, study results, or any other reason.
• Use of immunosuppressant in the 28 days or 5 half-lives (whichever is longer) prior to the first study drug administration.

Sponsors & Collaborators

• Thryv Therapeutics, Inc.: lead

Study Sites (1)

Altasciences

Montreal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: July 18, 2024
• Study Start: May 15, 2024
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: May 13, 2025

Record last verified: 2024-07

Locations

CA (1)