Renal Impairment, Heart Failure
Conditions
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.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in First 24hr Urinary Sodium (UNa) (Part 1) | Baseline (Day -1) and 0-24 hours postdose on Treatment Day 1 of each treatment period | Urine was collected at Treatment Day -1 and Treatment Day 1 at 0-2, 2-4, 4-6, 6-8, 8-12, 12-24 hour. The 24-hour cumulative natriuresis will be estimated by the amount of sodium excreted into urine over 24 hour period postdose, where amount of sodium is the product of sodium concentration and the volume of urine. The change from baseline in UNa from baseline (Treatment Day -1) and 24 hours post-dose on Treatment Day 1 were calculated. |
| N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Values at 24 Hours Post Last Morning Dose of Each Period (Part 2) | Day 15 for Periods 1, 2, and 3; Day 29 for Period 4 | B-type natriuretic peptide (BNP) is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function. Levels of BNP levels were assessed 24 hours post last morning dose of study drug for each treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 1 and Treatment Day 5 | Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24, 96, 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The Cmax was calculated for Treatment Days 1 and 5. |
| Trough Plasma Concentration (Ctrough) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 1 and Treatment Day 5 | Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24 , 96 , 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The Ctrough for was calculated for Treatment Days 1 and 5 |
| Time to Cmax (Tmax) of MK-7145(Treatment Days 1 and 5: Part 1) | Treatment Day 1 and Treatment Day 5 | Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24, 96 , 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The time to Cmax (Tmax) calculated for Treatment Days 1 and 5 |
| Apparent Terminal Half-life (t1/2) of MK-7145 (Part 1) | Treatment Day 1 and Treatment Day 5 | Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24, 96, 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The t1/2 was calculated. |
| Serum Creatinine Measured at 24 Hours Post Last Morning Dose of Each Period (Part 2) | Day 15 for Periods 1, 2, and 3; Day 29 for Period 4 | Blood samples were collected at 24 hours post last morning dose of each period to determine serum creatinine levels |
| Fold Change From Baseline for Serum Creatinine at 24-hours Post Treatment Day 5 Morning Dose (Part 1) | Baseline (predose Treatment Day 1) and 24 hours post morning dose on Treatment Day 5 of each treatment period (Part I) | Blood was collected predose on Treatment Day 1 and at 24 hours post morning dose on Treatment Day 5 to determine serum creatinine levels. Creatinine levels were log transformed and then fold change from baseline was calculated. |
| Maximum Plasma Concentration (Cmax) of MK-7145 (Part 2) | up to 24 hours post morning dose on up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 | Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 2-4 to determine the Cmax. |
| Trough Plasma Concentration (Ctrough) of MK-7145 (Part 2) | up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 | Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 to determine the Ctrough. |
| Time to Cmax (Tmax) of MK-7145(Part 2) | up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 | Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 to determine the Tmax. |
| Apparent Terminal Half-life (t1/2) of MK-7145 (Part 2) | up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 | Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 to determine the t1/2. |
| Area Under the Concentration-time Curve From Time Zero to 24 Hours After Dosing (AUC0-24hr) of MK-7145 (Part 2) | up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 | Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3-4 to determine the AUC0-24hr |
| Area Under the Concentration-time Curve From Time Zero to 24 Hours After Dosing (AUC0-24hr) of MK-7145 (Treatment Days 1 and 5: Part 1) | up to 24 hours post-dose on Treatment Day 1 and Treatment Day 5 | Blood samples for pharmacokinetic analysis were collected on Day 4 (Treatment Day 1) through Day 8 (Treatment Day 5) at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24 , 96, 101, 104, 106, 108, 110 and 120 hours (relative to Day 4 dosing). The AUC0-24 was calculated for Days 1 and 5 |
Participant flow
Pre-assignment details
Study was terminated early due to lack of efficacy of MK-7145. Only 11 participants were enrolled and dosed in Part 1. Period 3 of Part 1 was not conducted. No participants were enrolled in the planned Part 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| MK-7145 8 mg→Furosemide 40 mg 2 x Day (BID)→ MK-7145 16 mg Part 1: Participants receive 8 mg MK-7145 once daily (QD) for 5 days, then furosemide 40 mg BID for 5 days and then 16 mg MK-7145 QD for 5 days. Each treatment period was separated by a 3-day wash-out. | 11 |
| Furosemide/Torsemide→MK-7145 10 mg→MK-7145 16 mg→MK-7145 24 mg Part 2: Participants receive Furosemide/Torsemide for 2 weeks , then 10 mg MK-7145 for 14 days, then MK-7145 16 mg for 14 days and then MK-7145 24 mg for 28 days. Each treatment period was separated by a 3-day wash-out. | 0 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part 1 | Study Terminated by Sponsor | 10 | 0 |
| Part 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | MK-7145 8 mg→Furosemide 40 mg 2 x Day (BID)→ MK-7145 16 mg | Total |
|---|---|---|
| Age, Continuous | 61.4 Years STANDARD_DEVIATION 16 | 61.4 Years STANDARD_DEVIATION 16 |
| Sex: Female, Male Female | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 11 | 5 / 10 | 3 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 1 / 11 |
Outcome results
Primary
Change From Baseline in First 24hr Urinary Sodium (UNa) (Part 1)
Urine was collected at Treatment Day -1 and Treatment Day 1 at 0-2, 2-4, 4-6, 6-8, 8-12, 12-24 hour. The 24-hour cumulative natriuresis will be estimated by the amount of sodium excreted into urine over 24 hour period postdose, where amount of sodium is the product of sodium concentration and the volume of urine. The change from baseline in UNa from baseline (Treatment Day -1) and 24 hours post-dose on Treatment Day 1 were calculated.
Time frame: Baseline (Day -1) and 0-24 hours postdose on Treatment Day 1 of each treatment period
Population: All participants who received at least 1 dose of study drug and who complied with the protocol sufficiently. One participant did not participate for several time intervals on Period 2: Day 8 due to being unwell, and data from this day of this participant were excluded from the analysis. Part 1: Period 3 was not conducted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Change From Baseline in First 24hr Urinary Sodium (UNa) (Part 1) | 11.0 mEq |
| Furosemide 40 mg BID (Part 1: Period 2) | Change From Baseline in First 24hr Urinary Sodium (UNa) (Part 1) | 109.5 mEq |
95% CI: [-138, -59.1]Linear mixed effect model
Primary
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Values at 24 Hours Post Last Morning Dose of Each Period (Part 2)
B-type natriuretic peptide (BNP) is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function. Levels of BNP levels were assessed 24 hours post last morning dose of study drug for each treatment period.
Time frame: Day 15 for Periods 1, 2, and 3; Day 29 for Period 4
Population: Part 2 of the study was not conducted. No participants were enrolled.
Secondary
Apparent Terminal Half-life (t1/2) of MK-7145 (Part 1)
Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24, 96, 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The t1/2 was calculated.
Time frame: Treatment Day 1 and Treatment Day 5
Population: All participants who received at least 1 dose of MK-7145 and who complied with the protocol sufficiently and had data available for endpoint. t1/2 could not be estimated due to insufficient terminal phase sample. Part 1: Period 3 was not conducted.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Apparent Terminal Half-life (t1/2) of MK-7145 (Part 1) | Treatment Day 1 | NA hours |
| MK-7145 8 mg (Part 1: Period 1) | Apparent Terminal Half-life (t1/2) of MK-7145 (Part 1) | Treatment Day 5 | NA hours |
Secondary
Apparent Terminal Half-life (t1/2) of MK-7145 (Part 2)
Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 to determine the t1/2.
Time frame: up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4
Population: No participants were enrolled in Part 2 of the study.
Secondary
Area Under the Concentration-time Curve From Time Zero to 24 Hours After Dosing (AUC0-24hr) of MK-7145 (Part 2)
Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3-4 to determine the AUC0-24hr
Time frame: up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4
Population: No participants were enrolled in Part 2 of the study.
Secondary
Area Under the Concentration-time Curve From Time Zero to 24 Hours After Dosing (AUC0-24hr) of MK-7145 (Treatment Days 1 and 5: Part 1)
Blood samples for pharmacokinetic analysis were collected on Day 4 (Treatment Day 1) through Day 8 (Treatment Day 5) at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24 , 96, 101, 104, 106, 108, 110 and 120 hours (relative to Day 4 dosing). The AUC0-24 was calculated for Days 1 and 5
Time frame: up to 24 hours post-dose on Treatment Day 1 and Treatment Day 5
Population: All participants who received at least 1 dose of MK-7145, who complied with the protocol sufficiently and had data available for endpoint. Part 1: Period 3 was not conducted
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Area Under the Concentration-time Curve From Time Zero to 24 Hours After Dosing (AUC0-24hr) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 1 | 158 nM*hr | Geometric Coefficient of Variation 49.2 |
| MK-7145 8 mg (Part 1: Period 1) | Area Under the Concentration-time Curve From Time Zero to 24 Hours After Dosing (AUC0-24hr) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 5 | 485 nM*hr | Geometric Coefficient of Variation 50.4 |
Secondary
Fold Change From Baseline for Serum Creatinine at 24-hours Post Treatment Day 5 Morning Dose (Part 1)
Blood was collected predose on Treatment Day 1 and at 24 hours post morning dose on Treatment Day 5 to determine serum creatinine levels. Creatinine levels were log transformed and then fold change from baseline was calculated.
Time frame: Baseline (predose Treatment Day 1) and 24 hours post morning dose on Treatment Day 5 of each treatment period (Part I)
Population: All participants who received at least 1 dose of study drug , who complied with the protocol sufficiently and had data available for endpoint. Part 1: Period 3 was not conducted.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Fold Change From Baseline for Serum Creatinine at 24-hours Post Treatment Day 5 Morning Dose (Part 1) | 1.30 mg/dL |
| Furosemide 40 mg BID (Part 1: Period 2) | Fold Change From Baseline for Serum Creatinine at 24-hours Post Treatment Day 5 Morning Dose (Part 1) | 1.18 mg/dL |
90% CI: [0.99, 1.22]Mixed Linear Effects Model
Secondary
Maximum Plasma Concentration (Cmax) of MK-7145 (Part 2)
Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 2-4 to determine the Cmax.
Time frame: up to 24 hours post morning dose on up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4
Population: No participants were enrolled in Part 2 of the study.
Secondary
Maximum Plasma Concentration (Cmax) of MK-7145 (Treatment Days 1 and 5: Part 1)
Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24, 96, 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The Cmax was calculated for Treatment Days 1 and 5.
Time frame: Treatment Day 1 and Treatment Day 5
Population: All participants who received at least 1 dose of MK-7145, who complied with the protocol sufficiently and had data available for endpoint. Part 1: Period 3 was not conducted
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Maximum Plasma Concentration (Cmax) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 1 | 10.2 nM | Geometric Coefficient of Variation 57.9 |
| MK-7145 8 mg (Part 1: Period 1) | Maximum Plasma Concentration (Cmax) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 5 | 26.0 nM | Geometric Coefficient of Variation 50.3 |
Secondary
Serum Creatinine Measured at 24 Hours Post Last Morning Dose of Each Period (Part 2)
Blood samples were collected at 24 hours post last morning dose of each period to determine serum creatinine levels
Time frame: Day 15 for Periods 1, 2, and 3; Day 29 for Period 4
Population: No participants were enrolled in Part 2 of the study.
Secondary
Time to Cmax (Tmax) of MK-7145(Part 2)
Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 to determine the Tmax.
Time frame: up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4
Population: No participants were enrolled in Part 2 of the study.
Secondary
Time to Cmax (Tmax) of MK-7145(Treatment Days 1 and 5: Part 1)
Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24, 96 , 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The time to Cmax (Tmax) calculated for Treatment Days 1 and 5
Time frame: Treatment Day 1 and Treatment Day 5
Population: All participants who received at least 1 dose of MK-7145 who complied with the protocol sufficiently and had data available for endpoint. Part 1: Period 3 was not conducted.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Time to Cmax (Tmax) of MK-7145(Treatment Days 1 and 5: Part 1) | Treatment Day 1 | 10.0 hours |
| MK-7145 8 mg (Part 1: Period 1) | Time to Cmax (Tmax) of MK-7145(Treatment Days 1 and 5: Part 1) | Treatment Day 5 | 5.0 hours |
Secondary
Trough Plasma Concentration (Ctrough) of MK-7145 (Part 2)
Blood samples taken at predose, 0.5, 1, 2, 5, 8, 12, 14 and 24 hours postdose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4 to determine the Ctrough.
Time frame: up to 24 hours post morning dose on Days 1 and 14 of Period 2 and Day 14 of Periods 3 and 4
Population: No participants were enrolled in Part 2 of the study.
Secondary
Trough Plasma Concentration (Ctrough) of MK-7145 (Treatment Days 1 and 5: Part 1)
Blood samples for pharmacokinetic analysis were collected on Treatment Day 1 through Treatment Day 5 at the following time points: Predose, 3, 5, 6, 8, 10, 12, 14, 18, 24 , 96 , 101, 104, 106, 108, 110 and 120 hours (relative to Treatment Day 1 dosing). The Ctrough for was calculated for Treatment Days 1 and 5
Time frame: Treatment Day 1 and Treatment Day 5
Population: All participants who received at least 1 dose of MK-7145, who complied with the protocol sufficiently and had data available for endpoint. Ctrough for MK-7145 8 mg arm could not be estimated due to insufficient terminal phase sample. Part 1: Period 3 was not conducted.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MK-7145 8 mg (Part 1: Period 1) | Trough Plasma Concentration (Ctrough) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 1 | NA nM |
| MK-7145 8 mg (Part 1: Period 1) | Trough Plasma Concentration (Ctrough) of MK-7145 (Treatment Days 1 and 5: Part 1) | Treatment Day 5 | NA nM |