A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JX09 in Healthy Subjects.

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, multi-part, single and multiple ascending dose study in healthy adult to test the safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect of JX09 when administered to healthy adult subjects.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multi-Part, Single and Multiple Ascending Dose Study of JX09 in Healthy Adult Participants

Conditions
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Resistant Hypertension

Intervention / Treatment
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* Drug: JX09 or placebo SAD
* Drug: JX09 or placebo MAD
* Drug: JX09


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 55 years (inclusive) In good health as deemed by the Investigator through a medical evaluation, including medical history, physical examination, and laboratory tests Body mass index (BMI) between 18 and 32 kg/m2, with a minimum weight of 50 kg at Screening Exclusion Criteria: Clinically significant oncologic, infectious, cardiovascular, pulmonary, hepatic, gastrointestinal, hematologic, metabolic, endocrine, neurologic, immunologic, renal, psychiatric, or other condition that in the opinion of the Investigator or Medical Monitor would make is unsafe for the participant to join the study or fulfill its requirements. A clinical abnormality or abnormal laboratory parameter(s) in the opinion of the Investigator or Medical Monitor is likely to introduce additional risk or will affect data interpretation. Postural tachycardia or hypotension. Female of childbearing potential who is pregnant, lactating, or planning to become pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-Blind, Placebo-Controlled, Multi-Part
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ascending Single Doses<br>48 participants, 6 single ascending dose (SAD) cohorts (Cohorts 1 to 6). Within each cohort, 8 participants will be randomized in a 6:2 ratio, 6 participants receiving JX09 and 2 receiving placebo | Drug: JX09 or placebo SAD<br>* For Part 1 SAD: JX09/placebo in capsule will be administered as a single oral dose. The nominal dose escalation scheme for the cohorts is 1, 3, 10, 30, 100, and 300 mg.<br>|
| Experimental: Ascending Multiple Doses<br>32 participants, 4 multiple ascending dose (MAD) cohorts (Cohorts 7 to 10). Within each cohort, 8 participants will be randomized in a 6:2 ratio, 6 participants receiving JX09 and 2 receiving placebo | Drug: JX09 or placebo MAD<br>* For Part 2 MAD: JX09/placebo in capsule will be administered for 11 days (once daily) The nominal dose escalation scheme for the cohorts is 2, 5, 10 and 20 mg.<br>|
| Experimental: Food Effect<br>12 participants,1 single-dose food effect (FE) cohort (Cohort 11), open-label, two-sequence, two-period, crossover design, participants will be randomly assigned to 1 of the 2 crossover sequences | Drug: JX09<br>* For Part 3 FE: JX09 in capsule will be administered as a two single oral doses separated by 15 days. The nominal dose is 10 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events and serious adverse events in health subjects. | The number of AEs and SAEs by using Common Terminology Criteria for Adverse Events (CTCAE) V5.0 | For SAD cohort,11 days, from Day 1 to Day 11; for MAD cohort,21 days, from Day 1 to Day 21; for food effect cohort,26 days, from Day 1 to Day 26 | 
| Clinically significant change from baseline in physical examinations in health subjects | The number of events that clinically significant change from baseline in physical examinations by measuring general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest, abdomen, skin, neurological extremities, etc. | For SAD cohort,11 days, from Day 1 to Day 11; for MAD cohort,21 days, from Day 1 to Day 21; for food effect cohort,26 days, from Day 1 to Day 26 | 
| Clinically significant change from baseline in vital signs in health subjects | The number of events that clinically significant change from baseline in vital signs by measuring heart rate, blood pressure, temperature, and respiratory rate. | For SAD cohort,11 days, from Day 1 to Day 11; for MAD cohort,21 days, from Day 1 to Day 21; for food effect cohort,26 days, from Day 1 to Day 26 | 
| Clinically significant change from baseline in electrocardiograms in health subjects | The number of events that clinically significant change from baseline in electrocardiograms by measuring heart rate, PR, QRS, QT and QTc interval. | For SAD cohort,11 days, from Day 1 to Day 11; for MAD cohort,21 days, from Day 1 to Day 21; for food effect cohort,26 days, from Day 1 to Day 26 | 
| Clinically significant change from baseline in clinical laboratory tests in health subjects | The number of events that clinically significant change from baseline in clinical laboratory tests by measuring clinical chemistry panel, complete blood count and coagulation. | For SAD cohort,11 days, from Day 1 to Day 11; for MAD cohort,21 days, from Day 1 to Day 21; for food effect cohort,26 days, from Day 1 to Day 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic parameters after a single ascending dose in health subjects | Area under the Concentration time Curve from Time 0 to the Last Measurable Concentration (AUC0-t) by measuring blood plasma | From Day 1 to Day 11 | 
| Plasma pharmacokinetic parameters after a single ascending dose in health subjects | Area under the Concentration-time Curve from Time 0 to 24 hour (AUC0-24) by measuring blood plasma | From Day 1 to Day 11 | 
| Plasma pharmacokinetic parameters after a single ascending dose in health subjects | Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) by measuring blood plasma | From Day 1 to Day 11 | 
| Plasma pharmacokinetic parameters after a single ascending dose in health subjects | Peak plasma concentration (CMAX) by measuring blood plasma | From Day 1 to Day 11 | 
| Plasma pharmacokinetic parameters after a single ascending dose in health subjects | Time of maximum concentration (TMAX) by measuring blood plasma | From Day 1 to Day 11 | 
| Plasma pharmacokinetic parameters after multiple ascending dose in health subjects | Peak plasma concentration (CMAX) by measuring blood plasma | On day 1 and day 11 | 
| Plasma pharmacokinetic parameters after multiple ascending dose in health subjects | Time of maximum concentration (TMAX) by measuring blood plasma | On day 1 and day 11 | 
| Plasma pharmacokinetic parameters after multiple ascending dose in health subjects | Area under the Concentration time Curve from Time 0 to the Last Measurable Concentration (AUC0-t) by measuring blood plasma | On day 1 and day 11 | 
| Plasma pharmacokinetic parameters after multiple ascending dose in health subjects | Area under the Concentration-time Curve from Time 0 to 24 hour (AUC0-24) by measuring blood plasma | On day 1 and day 11 | 
| Plasma pharmacokinetic parameters after multiple ascending dose in health subjects | Concentration at end of dosing interval by measuring blood plasma | From day 2 to day 11 | 
| Plasma pharmacokinetic parameters in health subjects under fed and fasted conditions | Area under the Concentration time Curve from Time 0 to the Last Measurable Concentration (AUC0-t) by measuring blood plasma | From day 1 to day 5 and on day 11, From day 16 to day 20 and day 26 | 
| Plasma pharmacokinetic parameters in health subjects under fed and fasted conditions | Area under the Concentration-time Curve from Time 0 to 24 hour (AUC0-24) by measuring blood plasma | From day 1 to day 5 and on day 11, From day 16 to day 20 and day 26 | 
| Plasma pharmacokinetic parameters in health subjects under fed and fasted conditions | Area under the Concentration-time Curve from Time 0 to Infinity (AUC0-inf) by measuring blood plasma | From day 1 to day 5 and on day 11, From day 16 to day 20 and day 26 | 
| Urine pharmacokinetic parameters after multiple ascending dose in health subjects | Cumulative amount of drug excreted by measuring urine | on day 1 and day 11 | 
| Urine pharmacokinetic parameters after multiple ascending dose in health subjects | Fraction of the dose excreted renally by measuring urine | on day 1 and day 11 | 
| Urine pharmacokinetic parameters after multiple ascending dose in health subjects | Renal clearance by measuring urine | on day 1 and day 11 | 
| Plasma pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of aldosterone by measuring blood plasma | From Day -1 to Day 5 and Day 11 for SAD cohort and from Day -2 to Day 1 and from Day 7 to Day 15 and Day 21 for MAD cohort | 
| Plasma pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of cortisol by measuring blood plasma | From Day -1 to Day 5 and Day 11 for SAD cohort and from Day -2 to Day 1 and from Day 7 to Day 15 and Day 21 for MAD cohort | 
| Plasma pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of corticosterone by measuring blood plasma | From Day -1 to Day 5 and Day 11 for SAD cohort and from Day -2 to Day 1 and from Day 7 to Day 15 and Day 21 for MAD cohort | 
| Urine pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of sodium by measuring 24-hour urine level | On Day 1 for SAD cohort and on Day -1 and 11 for MAD cohort | 
| Urine pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of potassium by measuring 24-hour urine level | On Day 1 for SAD cohort and on Day -1 and 11 for MAD cohort | 
| Urine pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of aldosterone by measuring 24-hour urine level | On Day 1 for SAD cohort and on Day -1 and 11 for MAD cohort | 
| Urine pharmacodynamic parameters after a single ascending dose or multiple ascending dose in health subjects | Change from baseline of cortisol by measuring 24-hour urine level | On Day 1 for SAD cohort and on Day -1 and 11 for MAD cohort | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Health Volunteer, Pharmacokinetic, Food effect