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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 |
|---|---|---|---|
| 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. |
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| 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. |
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| Multiple Ascending Dose (MAD) THRV-1268 | Experimental | 3 dosing cohorts will receive THRV-1268 in the morning on Day 1 to Day 7. |
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| Single Ascending Dose (SAD) Placebo | Placebo Comparator | 5 dosing cohorts will receive a single oral dose of placebo. |
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| 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. |
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| Multiple Ascending Dose (MAD) Placebo |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| THRV-1268 | Drug | THRV-1268 a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic LQT-1268 AUC0-t | Area under the concentration-time curve (AUC) from time 0 to the time of the last | SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7 |
| Pharmacokinetic LQT-1268 Cmax |
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Inclusion Criteria:
1.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.
3.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:
One of the following double-barrier contraception methods used from Screening through at least 30 days from last study dose
Physiological postmenopausal status, defined as the absence of menses for at least 12 months following cessation of all exogenous hormonal treatments (without an alternative medical condition) at Screening and prior to the first study drug administration and have follicle stimulating hormone (FSH) levels ≥ 40 mIU/mL at Screening (If subject is postmenopausal and has an FSH of < 40 mIU/mL, but meets all other criteria in (1) or (2) above as well as all the other inclusion criteria, screening estradiol serum level must be equal to or below 150 pmol/L. In the case of hysterectomy, if FSH and estradiol do not meet the criteria, eligibility for study participation will be based on medical judgment.).
Or
Surgically sterile, defined as those who have had hysterectomy, bilateral oophorectomy and/or bilateral salpingectomy, or bilateral tubal ligation.
5.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.
6.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.
7.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).
10.Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings in the physical examination (including vital signs) and/or ECG, as determined by an Investigator.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Altasciences | Montreal | Quebec | H3P 3P1 | Canada |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| Placebo Comparator |
3 dosing cohorts will receive placebo in the morning from Day 1 to Day 7. |
|
| Placebo | Other | Matching placebo |
|
Maximum observed plasma drug concentration
| SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7 |
| Pharmacokinetic LQT-1268 Tmax | Time to maximum observed plasma drug concentration | SAD: Day 1; Food Effect: Serially on Day 1 and Day 8; MAD: Serially on Day 1 and 7 |
| Pharmacokinetic LQT-1268 t1/2 | Time to maximum observed plasma drug concentration | 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 | Amount of the administered dose recovered over the entire 24-hour interval | SAD: Day 1; MAD: Serially on Day 1 and 7 |
| Urine Pharmacokinetics of LQT-1268: Fe | Percentage of the administered dose recovered over the entire 24-hour interval | SAD: Day 1; MAD: Serially on Day 1 and 7 |
| Urine Pharmacokinetics of LQT-1268: Ae0-t | Amount excreted unchanged in urine over a given time interval | SAD: Day 1; MAD: Serially on Day 1 and 7 |
| Plasma Pharmacokinetics of LQT-1268: Ctrough | Concentration of drug in the blood immediately before the next dose is administered | MAD: Days 3-6 |
| Plasma Pharmacokinetics of LQT-1268: Rac(AUC) | Drug accumulation ratio | MAD: Day 7 |
| Plasma Pharmacokinetics of LQT-1268: Rac(Cmax) | Drug accumulation ratio | MAD: Day 7 |
| D013568 |
| Pathological Conditions, Signs and Symptoms |