Conditions: Renal Impairment Heart Failure
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 11
Healthy volunteers: no

Brief summary:
Part I is a 3-period, active comparator-controlled, fixed sequence study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-7145 compared to furosemide in participants with moderate-to-severe renal insufficiency (RI) without heart failure (HF). Primary hypothesis for Part I is that at least one well-tolerated dose of MK-7145 will produce a greater 24hr urinary excretion of sodium (UNa) on the 1st day of MK-7145 dosing than 80 mg furosemide (on the 1st day of furosemide dosing) in participants with moderate-to-severe RI. If MK-7145 is safe at natriuretic doses in RI in Part I of this study, MK-7145 will be investigated in participants with heart failure (HF) and RI (Part II).

Part II is 4 period, fixed sequence, active comparator controlled (in Period 1), titration (in Periods 2, 3 and 4) study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a titration regimen of MK-7145 compared to an optimized stable maintenance regimen of furosemide or torsemide in participants with New York Heart Association (NYHA) Class II and III heart failure and moderate or severe renal insufficiency. The primary hypothesis for Part II is that at least one dose of MK-7145, titrated according to a fixed dose titration regimen, will be associated with a reduction in N-terminal pro-brain natriuretic peptide (NT-proBNP) compared to furosemide or torsemide (at 24 hours post morning dose on the last dosing day of each period) in participants with NYHA class II/III HF with moderate or severe RI.

Detailed description:

Arms:
arm 1: Single daily dose of 8 mg MK-7145 for 5 days, capsules, orally administered in a fasted state arm 2: Two daily doses of one 40 mg Furosemide tablet for 5 days administered in a fasted state arm 3: Single daily dose of 16 mg MK-7145 for 5 days, capsules, orally administered in a fasted state arm 4: Run-in of stable, clinically optimized maintenance dose regimen of furosemide or torsemide for at least 2 weeks arm 5: Single daily dose of 10 mg MK-7145 for 14 days, capsules, orally administered in a fasted state arm 6: Single daily dose of 16 mg MK-7145 for 14 days, capsules, orally administered in a fasted state arm 7: Single dose of 24 mg MK-7145 for 28 days, capsules, orally administered in a fasted state

Interventions: intervention 1: MK-7145 intervention 2: Furosemide intervention 3: Torsemide
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol document: