Clinical trial NCT05500820: Study With CIN-107 Following Multiple Oral Ascending Doses in Healthy Subjects
Official title: A Randomized, Double-Blind Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CIN-107 Following Multiple Oral Doses in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Keywords: pharmacokinetics (PK), metabolism, baxdrostat
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-08-15
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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).
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive.
3. Nonsmokers who have not used nicotine-containing products for at least 6 months prior to the Screening Visit.

Exclusion Criteria:

1. 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.
2. A personal or family history of long QT syndrome, Torsades de Pointes, or other complex ventricular arrhythmias, or family history of sudden death.
3. History of, or current, clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, or atrial fibrillation.
4. Prolonged QTcF (\>450 msec) based on the average of triplicate ECGs.
5. Seated blood pressure higher than 150/90 mmHg or lower than 90/50 mmHg.
6. Resting heart rate higher than 100 bpm or lower than 50 bpm , sinus node dysfunction, or clinically significant heart block.
7. Temperature (T) greater than 37.6o C (99.68o F, measured orally), and respiration rate less than 12 and greater than 20 breaths/minute.
8. 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).
9. Serum potassium \> upper limit of normal of the reference range (ULN) and serum sodium \< lower limit of normal of the reference range (LLN).
10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values \> 1.2 ULN.
11. Positive for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody, or Hepatitis B surface antigen (HBsAg).
12. A known history of porphyria, myopathy, or an active liver disease.
13. 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.
14. Typical consumption of ≥14 alcoholic drinks weekly.
15. Surgical procedures within 4 weeks of check-in or planned elective surgery during the study period.
16. Currently undergoing treatment with weight loss medication or prior weight loss surgery (eg, gastric bypass surgery).
17. Pregnant, breastfeeding, or planning to become pregnant during the study.

Primary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: up to Day 15
measure: Time to maximum plasma concentration (Tmax)
timeFrame: up to Day 15
measure: Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last])
timeFrame: up to Day 15
measure: Area under the curve from time 0 to infinity
timeFrame: up to Day 15
measure: Area under the curve over a dosing interval (tau)
timeFrame: up to Day 15
measure: Area under the plasma concentration-time curve (AUC) from time 0 to 24 hours
timeFrame: up to Day 2
measure: Percent of AUC extrapolated
timeFrame: up to Day 15
measure: Terminal phase elimination half-life
timeFrame: up to Day 15
measure: Apparent plasma clearance
timeFrame: up to Day 15
measure: Apparent volume of distribution
timeFrame: Up to Day 15
measure: The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae)
timeFrame: up to Day 15
measure: Renal clearance (CLR Calculated as Ae/AUC) of CIN-107 and CIN-107-M
timeFrame: up to Day 15
measure: Fraction of the dose excreted renally (fe)
timeFrame: up to Day 15
measure: Number of patients experiencing adverse events (AEs)
timeFrame: up to Day 15
measure: Number of patients experiencing adverse drug reactions
timeFrame: up to Day 15
measure: Number of patients experiencing serious adverse events (SAEs)
timeFrame: up to Day 15
measure: Plasma concentration of aldosterone
timeFrame: up to Day 15
measure: Plasma renin activity
timeFrame: up to Day 15
measure: Plasma concentration of cortisol (free and total)
timeFrame: up to Day 15
measure: Plasma concentration of ACTH (Adrenocorticotropic hormone)
timeFrame: up to Day 15
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
Study officials:
affiliation: Medpace Clinical Pharmacology Unit
name: Leela Vrishabhendra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Freeman MW, Bond M, Murphy B, Hui J, Isaacsohn J. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023 Jan;46(1):108-118. doi: 10.1038/s41440-022-01070-4. Epub 2022 Oct 20.