Study With CIN-107 Following Multiple Oral Ascending Doses in Healthy Subjects
- Registration Number
- NCT05500820
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 4: 2.5 mg CIN-107 CIN-107 Subjects on a normal salt diet Cohort 1: 2.5 mg CIN-107 CIN-107 Subjects on a low salt diet Cohort 2: 5.0 mg CIN-107 CIN-107 Subjects on a low salt diet Cohort 5: 0.5 mg CIN-107 CIN-107 Subjects on a normal salt diet Cohort 1: 2.5 mg matching placebo Matching Placebo Subjects on a low salt diet Cohort 2: 5.0 mg matching placebo Matching Placebo Subjects on a low salt diet Cohort 3: 1.5 mg matching placebo Matching Placebo Subjects on a normal salt diet Cohort 4: 2.5 mg matching placebo Matching Placebo Subjects on a normal salt diet Cohort 5: 0.5 mg matching placebo Matching Placebo Subjects on a normal salt diet Cohort 3: 1.5 mg CIN-107 CIN-107 Subjects on a normal salt diet
- Primary Outcome Measures
Name Time Method Time to maximum plasma concentration (Tmax) up to Day 15 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.
Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last]) up to Day 15 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.
Area under the curve from time 0 to infinity up to Day 15 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.
Area under the curve over a dosing interval (tau) up to Day 15 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.
Area under the plasma concentration-time curve (AUC) from time 0 to 24 hours up to Day 2 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.
Maximum plasma concentration (Cmax) up to Day 15 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.
Apparent plasma clearance up to Day 15 This PK parameter will be determined for CIN-107 using plasma concentration data.
Apparent volume of distribution Up to Day 15 This PK parameter will be determined for CIN-107 using plasma concentration data.
The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae) up to Day 15 This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)
Renal clearance (CLR Calculated as Ae/AUC) of CIN-107 and CIN-107-M up to Day 15 This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M)
Fraction of the dose excreted renally (fe) up to Day 15 This PK parameter will be calculated using the urine concentrations of CIN-107
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 Percent of AUC extrapolated up to Day 15 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.
Terminal phase elimination half-life up to Day 15 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Medpace Clinical Pharmacology Unit
🇺🇸Cincinnati, Ohio, United States