A Study of MK-7145 in Participants With Renal Insufficiency (Part I) and Heart Failure With Renal Insufficiency (Part II) (MK-7145-011)

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.


Eligibility Criteria:
Inclusion Criteria:

Parts I and II

* If female, must be of non-child bearing potential or, if of child-bearing potential agrees to use at least 2 acceptable contraceptive measures
* Body Mass Index (BMI) \>=17.5 and \<=38 kg/m\^2
* No present history of clinically significant uncontrolled arrhythmias on electrocardiogram (ECG)
* Nonsmoker or a light smoker consuming up to an average of 20 cigarettes (or equivalent tobacco product) per day.

Part I Only

- Estimated creatinine clearance of ≤45 mL/min.

Part II Only

* Class II or III heart failure as specified by the New York Heart Association (NYHA) functional classification for heart failure with NT-proBNP \>=1000 pg/mL on clinically optimized therapy with a stable dose (for at least 2 weeks) of furosemide or torsemide
* Estimated creatinine clearance of ≤45 mL/min

Exclusion Criteria:

Parts I and II

* Mentally or legally institutionalized and/or incapacitated, has significant emotional problems or has a history of a clinically significant psychiatric disorder over the last 5 years. This includes any mood disorder requiring concomitant use of lithium
* Diagnosed with acute coronary syndrome or acute cardiovascular (CV) event, or has been hospitalized for HF exacerbation within less than 3 months of study entry
* Unstable angina pectoris
* Diabetes requiring high dose peroxisome proliferator-activated receptor (PPAR) antagonist (e.g. \>30 mg of pioglitazone) or unstable insulin use
* Infectious disease requiring concomitant use of aminoglycosides
* Low plasma potassium (hypokalemia)
* Recent (within 6 months) history of stroke, uncontrolled seizures, or uncontrolled major neurological disorder
* Urinary retention, hydronephrosis or hydroureter
* Active nephrocalcinosis, nephrolithiasis, or hypercalciuria
* Functional disability that can interfere with rising from a semi-recumbent position to the standing position
* History of malignant neoplastic disease
* Unable to refrain from the use of medication, including prescription and non-prescription drugs such as high-dose aspirin (≥325 mg/day), non-steroidal anti-inflammatory drugs (NSAIDs), human immunodeficiency virus (HIV) protease inhibitors (ritonavir, indinavir, nelfinavir), macrolide antibiotics (erythromycin, telithromycin, clarithromycin), chloramphenicol, azole antifungals (fluconazole, ketoconazole, itraconazole, nefazodone, aprepitant, verapamil, diltiazem, etc.), anticonvulsants and mood stabilizers (e.g., phenytoin, carbamazepine, oxcarbazepine), barbiturates (phenobarbital), HIV non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine, etravirine), rifampicin, modafinil, St John's wort, cyproterone (antiandrogen, progestin), etc. beginning approximately 2 weeks (or 5 half-lives), prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods) until the poststudy visit
* Consumes excessive amounts of alcohol, defined as greater than 5 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) per day
* Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
* Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks
* Regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 6 months