Abstract: FR-PO751
Results From a Phase 1 Study Demonstrating the Safety and Pharmacokinetics of the Aldosterone Synthase Inhibitor CIN-107 in Subjects With Varying Degrees of Renal Function
Session Information
- Hypertension and CVD: Clinical, Outcomes, Trials
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1502 Hypertension and CVD: Clinical‚ Outcomes‚ and Trials
Authors
- Freeman, Mason W., CinCor Pharma, Inc., Waltham, Massachusetts, United States
- Halvorsen, Yuan-Di, CinCor Pharma, Inc., Waltham, Massachusetts, United States
- Bond, Mary, CinRx Pharma, LLC, Cincinnati, Ohio, United States
- Murphy, Brian, CinRx Pharma, LLC, Cincinnati, Ohio, United States
- Isaacsohn, Jonathan, CinRx Pharma, LLC, Cincinnati, Ohio, United States
Background
Hypertension and chronic kidney disease are common comorbidities exacerbated by elevated aldosterone. CIN-107 is a selective inhibitor of aldosterone synthase with the potential to lower blood pressure and slow the progression of kidney disease. This phase 1 open-label study assessed the safety and pharmacokinetics (PK) of a single oral dose of CIN-107 in subjects with varying degrees of renal function.
Methods
Subjects enrolled into renal function groups based on estimated glomerular filtration rate (eGFR). The groups were control (eGFR ≥60mL/min), moderate to severe renal impairment (eGFR 15 to 59 mL/min), and kidney failure (eGFR <15mL/min, including subjects on dialysis). A single 10 mg CIN-107 dose was given, followed by 7 days of PK sampling (blood and urine). Safety was assessed based on adverse events, clinical laboratory evaluations, vital signs, ECGs, physical examinations, and weight measurements.
Results
32 subjects completed the study. There were no deaths, and only one mild drug-related adverse event (diarrhea) occurred. There were no clinically meaningful changes in laboratory values, vital signs, physical examinations, or ECGs. The plasma concentration-time curves of CIN-107 in all groups were qualitatively similar (Figure 1). The urine PK parameters in the moderate to severe renal impairment group were similar to control (12% excreted); however, inadequate urine production in the kidney failure group resulted in negligible excretion of CIN-107.
Conclusion
A single dose of CIN-107 was well tolerated in all subjects, including those with kidney failure. Renal impairment did not significantly impact systemic exposure or clearance of CIN-107, suggesting that dose adjustment due to PK differences in these patients is unnecessary, even in cases of advanced kidney disease.
Plsma 107 Concentr vs Time
Funding
- Commercial Support –