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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01558674
First received: March 16, 2012
Last updated: July 18, 2014
Last verified: July 2014

March 16, 2012
July 18, 2014
May 2014
May 2015   (final data collection date for primary outcome measure)
  • Change from baseline in first 24hr UNa (Part I) [ Time Frame: Baseline (Day 3 predose) and 0-24 hours postdose on Day 4 (first day of active treatment) of each treatment period (Treatments A,B and C) ] [ Designated as safety issue: No ]
  • NT-proBNP values at 24 hours post last dose (Part II) [ Time Frame: Day 14 for Periods 1-3 (Treatments D, E, and F); Day 28 of Period 4 (Treatment G) ] [ Designated as safety issue: No ]
  • Change from baseline in first 24hr natriuresis [ Time Frame: Baseline (Day 3 predose) and 24 hours postdose (Day 4) ] [ Designated as safety issue: No ]
  • AUC0-24hr on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve from time zero to 24 hours after dosing (AUC0-24hr) on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  • Cmax on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
  • Trough plasma concentration (Ctrough) on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  • Ctrough on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  • Tmax on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
  • Apparent terminal half-life (t1/2) on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  • t1/2 on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01558674 on ClinicalTrials.gov Archive Site
  • Fold change from baseline for serum creatinine (Part I) [ Time Frame: Baseline (predose Day 4; first day of active treatment) and Day 8 of each treatment period (Part I-Treatments A,B and C) ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve from time zero to 24 hours after dosing (AUC0-24hr) for MK-7145 (Part I) [ Time Frame: Day 4 (first day of active treatment) and Day 8 of Part I:Periods 1 and 3 (Treatments A, and C) ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) for MK-7145 (Part I) [ Time Frame: Day 4 (first day of active treatment) and Day 8 of Part I:Periods 1 and 3 (Treatments A, and C) ] [ Designated as safety issue: No ]
  • Trough plasma concentration (Ctrough) for MK-7145 (Part I) [ Time Frame: Day 4 (first day of active treatment) and Day 8 of Part I:Periods 1 and 3 (Treatments A, and C) ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) for MK-7145 (Part I) [ Time Frame: Day 4 (first day of active treatment) and Day 8 of Part I:Periods 1 and 3 (Treatments A, and C) ] [ Designated as safety issue: No ]
  • Apparent terminal half-life (t1/2) for MK-7145 (Part I) [ Time Frame: Day 4 (first day of active treatment) and Day 8 of Part I:Periods 1 and 3 (Treatments A, and C) ] [ Designated as safety issue: No ]
  • Serum creatinine measured at 24 hours post last dose (Part II) [ Time Frame: Day 14 for Periods 1-3 (Treatments D, E, and F) and Day 28 of Period 4 (Treatment G) ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve from time zero to 24 hours after dosing (AUC0-24hr) for MK-7145 (Part II) [ Time Frame: Day 1 of Period 2 (Treatment E) and Day 14 of Periods 2-4 (Treatments E, F, and G) ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) for MK-7145 (Part II) [ Time Frame: Day 1 of Period 2 (Treatment E) and Day 14 of Periods 2-4 (Treatments E, F, and G) ] [ Designated as safety issue: No ]
  • Trough plasma concentration (Ctrough) for MK-7145 (Part II) [ Time Frame: Day 1 of Period 2 (Treatment E) and Day 14 of Periods 2-4 (Treatments E, F, and G) ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) for MK-7145 (Part II) [ Time Frame: Day 1 of Period 2 (Treatment E) and Day 14 of Periods 2-4 (Treatments E, F, and G) ] [ Designated as safety issue: No ]
  • Apparent terminal half-life (t1/2) for MK-7145 (Part II) [ Time Frame: Day 1 of Period 2 (Treatment E) and Day 14 of Periods 2-4 (Treatments E, F, and G) ] [ Designated as safety issue: No ]
  • Baseline corrected peak diuresis [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
  • Fold change from baseline for serum creatinine [ Time Frame: Baseline (predose) Day 4 and 24 hours postdose ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of MK-7145 in Participants With Renal Insufficiency (Part I) and Heart Failure With Renal Insufficiency (Part II) (MK-7145-011)
A Two Part, Open-label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-7145 in Patients With Renal Insufficiency (Part I) and Heart Failure With Renal Insufficiency (Part II)

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 postdose on the last dosing day of each period) in participants with NYHA class II/III HF with moderate or severe RI.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Renal Impairment
  • Heart Failure
  • Drug: MK-7145 2 mg
  • Drug: MK-7145 8 mg
  • Drug: Furosemide
    Other Name: Lasix
  • Drug: Torsemide
  • Experimental: Treatment A (Part I:Period 1)
    Single daily dose of 8 mg MK-7145 for 5 days, capsules, orally administered in a fasted state
    Intervention: Drug: MK-7145 2 mg
  • Active Comparator: Treatment B (Part I:Period 2)
    Two daily doses of one 40 mg Furosemide tablet for 5 days administered in a fasted state
    Intervention: Drug: Furosemide
  • Experimental: Treatment C (Part I:Period 3)
    Single daily dose of 16 mg MK-7145 for 5 days, capsules, orally administered in a fasted state
    Interventions:
    • Drug: MK-7145 2 mg
    • Drug: MK-7145 8 mg
  • Active Comparator: Treatment D (Part II:Period1)
    Run-in of stable, clinically optimized maintenance dose regimen of furosemide or torsemide for at least 2 weeks
    Interventions:
    • Drug: Furosemide
    • Drug: Torsemide
  • Experimental: Treatment E (Part II:Period 2)
    Single daily dose of 10 mg MK-7145 for 14 days, capsules, orally administered in a fasted state
    Interventions:
    • Drug: MK-7145 2 mg
    • Drug: MK-7145 8 mg
  • Experimental: Treatment F (Part II:Period 3)
    Single daily dose of 16 mg MK-7145 for 14 days, capsules, orally administered in a fasted state
    Interventions:
    • Drug: MK-7145 2 mg
    • Drug: MK-7145 8 mg
  • Experimental: Treatment G (Part II:Period 4)
    Single dose of 24 mg MK-7145 for 28 days, capsules, orally administered in a fasted state
    Interventions:
    • Drug: MK-7145 2 mg
    • Drug: MK-7145 8 mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
26
May 2015
May 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact: Toll Free Number 1-888-577-8839
Australia,   New Zealand
 
NCT01558674
7145-011
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP