Study With CIN-107 Following Multiple Oral Ascending Doses in Healthy Subjects

Study Overview
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Brief Summary
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This is a randomized, double-blind, study to assess the safety, tolerability, PK, and PD of multiple oral doses of CIN-107 when administered to healthy adult subjects.

Official Title
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A Randomized, Double-Blind Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CIN-107 Following Multiple Oral Doses in Healthy Subjects

Conditions
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Hypertension

Intervention / Treatment
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* Drug: CIN-107
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects between the ages of 18 and 55 years, inclusive, in good health based on medical and psychiatric history, physical examination, ECG, orthostatic vital signs, and routine laboratory tests (blood chemistry, hematology, coagulation, and urinalysis). Body mass index (BMI) between 18 and 30 kg/m2, inclusive. Nonsmokers who have not used nicotine-containing products for at least 6 months prior to the Screening Visit. Exclusion Criteria: Actively participating in an experimental therapy study; received experimental therapy with a small molecule within 30 days of Day 1, or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of Day 1, or 5 half-lives, whichever is longer. A personal or family history of long QT syndrome, Torsades de Pointes, or other complex ventricular arrhythmias, or family history of sudden death. History of, or current, clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, or atrial fibrillation. Prolonged QTcF (>450 msec) based on the average of triplicate ECGs. Seated blood pressure higher than 150/90 mmHg or lower than 90/50 mmHg. Resting heart rate higher than 100 bpm or lower than 50 bpm , sinus node dysfunction, or clinically significant heart block. Temperature (T) greater than 37.6o C (99.68o F, measured orally), and respiration rate less than 12 and greater than 20 breaths/minute. Postural tachycardia (ie >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic blood pressure (SBP) of ≥20 mm Hg or DBP of ≥ 10 mm Hg when a person assumes a standing position). Serum potassium > upper limit of normal of the reference range (ULN) and serum sodium < lower limit of normal of the reference range (LLN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values > 1.2 ULN. Positive for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody, or Hepatitis B surface antigen (HBsAg). A known history of porphyria, myopathy, or an active liver disease. Positive drug or alcohol test result or a history of alcoholism or drug abuse within 2 years prior to the first dose of study drug as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition: DSM-IV. Typical consumption of ≥14 alcoholic drinks weekly. Surgical procedures within 4 weeks of check-in or planned elective surgery during the study period. Currently undergoing treatment with weight loss medication or prior weight loss surgery (eg, gastric bypass surgery). Pregnant, breastfeeding, or planning to become pregnant during the study.

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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 2.5 mg CIN-107<br>Subjects on a low salt diet | Drug: CIN-107<br>* A repeat oral dose of CIN-107 once daily for 10 days.<br>* Other names: baxdrostat;|
| Experimental: Cohort 2: 5.0 mg CIN-107<br>Subjects on a low salt diet | Drug: CIN-107<br>* A repeat oral dose of CIN-107 once daily for 10 days.<br>* Other names: baxdrostat;|
| Experimental: Cohort 3: 1.5 mg CIN-107<br>Subjects on a normal salt diet | Drug: CIN-107<br>* A repeat oral dose of CIN-107 once daily for 10 days.<br>* Other names: baxdrostat;|
| Experimental: Cohort 4: 2.5 mg CIN-107<br>Subjects on a normal salt diet | Drug: CIN-107<br>* A repeat oral dose of CIN-107 once daily for 10 days.<br>* Other names: baxdrostat;|
| Experimental: Cohort 5: 0.5 mg CIN-107<br>Subjects on a normal salt diet | Drug: CIN-107<br>* A repeat oral dose of CIN-107 once daily for 10 days.<br>* Other names: baxdrostat;|
| Placebo Comparator: Cohort 1: 2.5 mg matching placebo<br>Subjects on a low salt diet | Drug: Matching Placebo<br>* A repeat oral dose of matching placebo once daily for 10 days.<br>|
| Placebo Comparator: Cohort 2: 5.0 mg matching placebo<br>Subjects on a low salt diet | Drug: Matching Placebo<br>* A repeat oral dose of matching placebo once daily for 10 days.<br>|
| Placebo Comparator: Cohort 3: 1.5 mg matching placebo<br>Subjects on a normal salt diet | Drug: Matching Placebo<br>* A repeat oral dose of matching placebo once daily for 10 days.<br>|
| Placebo Comparator: Cohort 4: 2.5 mg matching placebo<br>Subjects on a normal salt diet | Drug: Matching Placebo<br>* A repeat oral dose of matching placebo once daily for 10 days.<br>|
| Placebo Comparator: Cohort 5: 0.5 mg matching placebo<br>Subjects on a normal salt diet | Drug: Matching Placebo<br>* A repeat oral dose of matching placebo once daily for 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first and last doses of CIN-107, as the data permit. | up to Day 15 | 
| Time to maximum plasma concentration (Tmax) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first and last doses of CIN-107, as the data permit. | up to Day 15 | 
| Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last]) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit. | up to Day 15 | 
| Area under the curve from time 0 to infinity | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit. | up to Day 15 | 
| Area under the curve over a dosing interval (tau) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit. | up to Day 15 | 
| Area under the plasma concentration-time curve (AUC) from time 0 to 24 hours | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data and following the first dose of CIN-107, as the data permit. | up to Day 2 | 
| Percent of AUC extrapolated | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit. | up to Day 15 | 
| Terminal phase elimination half-life | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data following the final dose of CIN-107, as the data permit. | up to Day 15 | 
| Apparent plasma clearance | This PK parameter will be determined for CIN-107 using plasma concentration data. | up to Day 15 | 
| Apparent volume of distribution | This PK parameter will be determined for CIN-107 using plasma concentration data. | Up to Day 15 | 
| The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae) | This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M) | up to Day 15 | 
| Renal clearance (CLR Calculated as Ae/AUC) of CIN-107 and CIN-107-M | This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M) | up to Day 15 | 
| Fraction of the dose excreted renally (fe) | This PK parameter will be calculated using the urine concentrations of CIN-107 | up to Day 15 | 
| Number of patients experiencing adverse events (AEs) |  | up to Day 15 | 
| Number of patients experiencing adverse drug reactions |  | up to Day 15 | 
| Number of patients experiencing serious adverse events (SAEs) |  | up to Day 15 | 
| Plasma concentration of aldosterone |  | up to Day 15 | 
| Plasma renin activity |  | up to Day 15 | 
| Plasma concentration of cortisol (free and total) |  | up to Day 15 | 
| Plasma concentration of ACTH (Adrenocorticotropic hormone) |  | up to Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics (PK), metabolism, baxdrostat