Renal Insufficiency
Conditions
Brief summary
This study will investigate and compare pharmacokinetics of a single 50 mg dose of odanacatib administered to participants with impaired renal/kidney function to those of a healthy matched control group. The primary hypothesis is that plasma AUC0-∞ of odanacatib in participants with impaired renal function is similar to that in matched healthy participants following a single 50 mg oral dose.
Interventions
DRUGMK-0822
A single oral dose (50 mg tablet) of MK-0822 will be administered on Day 1 after an overnight fast.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* Not currently pregnant, nursing or planning to be pregnant through-out the course of the study; individual agrees to use specified contraception per protocol requirement for duration of study. Note: All females must have a serum pregnancy test to ensure and document negative test results prior to inclusion in the study. * Body Mass Index (BMI) of up to 39.49kg/m\^2 * Assessed to be in good health, including no clinically significant cardiac abnormalities based on results from an electrocardiogram (ECG) performed at pre-screening and/or prior to administration of study drug. * Meets the requirements of the study in regard to current medication profile including: prescribed medications, caffeine, alcohol, over-the-counter drugs, herbals and nutritional products; with expected non-use of recreational (illicit) drugs associated with misuse, abuse and/or addiction. * Agrees to adhere to all smoking and dietary restrictions associated with the study. * Possess the ability to understand the study, grant voluntary informed consent, and willingly comply with all study requirements. Inclusion Criterion Specific to Participants with Renal/Kidney Insufficiency: * Creatinine clearance of \<30 mL/min Inclusion Criterion Specific to Healthy Volunteers: * Creatine clearance of ≥ 90 mL/min (for healthy volunteers)
Exclusion criteria
* Does not meet the age requirement, is mentally or legally incapacitated, has or is expected to have significant emotional problems, and/or a history of a clinically significant psychiatric disorder. * Diagnosed with a disease or medical condition which may pose a risk to the participant or may confound the study results. * Has demonstrated or suspected stenosis (narrowing) of the renal artery, and/or has had a renal transplant and/or kidney removal. * Has current, unstable, significant organ system disease(s) and/or cancer(s). * Has had a surgical procedure, donated 1 unit of blood or received another investigational study medication within 4 weeks prior to the study's first dose of investigational product. * Unable to refrain from or anticipates the use of any new medication, including prescription and non-prescription drugs and/or herbal remedies. Exceptions may include medications prescribed for prevention of disease or preservation of a healthy life. * Uses any medication or agent that has the potential to significantly alter renal/kidney function. * Unable to avoid taking diuretics (within 4 hours prior to and after dosing with the investigational product) or phosphate binders containing aluminum, calcium or lanthanum salts; iron supplements or other metal cations; antacids; or multivitamins containing iron or zinc (within 8 hours prior to dosing and 4 hours after dosing with the investigational product). Note: individuals prescribed to diuretics must be on a stable dose for at least 4 weeks prior to the study's start date in order to participate. * History of multiple and/or severe allergies, has had a life-threatening reaction to a drug or other agent, and/or inability to tolerate prescription or nonprescription drugs and/or food.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose | Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose | For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of AUC0-∞ (Total AUC). AUC0-∞ is a measure of total drug exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of MK-0822 After Single Dose | Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose | For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of Cmax. |
| Time to Maximum Concentration (Tmax) of MK-0822 After Single Dose | Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose | For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of Tmax. |
| Apparent Terminal Half-life (t1/2) of MK-0822 After Single Dose | Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose | For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of t1/2. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Severe Renal Insufficiency Group Single-dose administration of odanacatib 50 mg to participants with severe renal insufficiency. | 13 |
| Healthy Matched Control Group Single-dose administration of odanacatib 50 mg to healthy matched control participants. | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Severe Renal Insufficiency Group | Healthy Matched Control Group | Total |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 10.9 | 55.6 years STANDARD_DEVIATION 10 | 59.4 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 13 | 2 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose
For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of AUC0-∞ (Total AUC). AUC0-∞ is a measure of total drug exposure.
Time frame: Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose
Population: The per protocol population consisted of all matched participants who complied with the protocol sufficiently to ensure that results will likely exhibit the effects of treatment according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Severe Renal Insufficiency Group | Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose | 51.47 μM*hr |
| Healthy Matched Control Group | Area Under the Concentration-time Curve of MK-0822 From Time 0 to Infinity (AUC0-∞) After Single Dose | 32.12 μM*hr |
Comparison: Natural log-transformed plasma values were analyzed using an analysis of covariance (ANCOVA) model with a categorical factor for population (severe renal insufficiency participants, healthy matched control participants) and continuous covariates for age and body mass index (BMI). Data are back transformed to geometric least-squares mean ratio (GMR) (severe renal insufficiency / healthy) and 90% confidence intervals.90% CI: [1.15, 2.23]
Secondary
Apparent Terminal Half-life (t1/2) of MK-0822 After Single Dose
For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of t1/2.
Time frame: Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose
Population: The per protocol population consisted of all matched participants who complied with the protocol sufficiently to ensure that results will likely exhibit the effects of treatment according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Renal Insufficiency Group | Apparent Terminal Half-life (t1/2) of MK-0822 After Single Dose | 73.9 hr | Geometric Coefficient of Variation 25 |
| Healthy Matched Control Group | Apparent Terminal Half-life (t1/2) of MK-0822 After Single Dose | 80.0 hr | Geometric Coefficient of Variation 20.7 |
Secondary
Maximum Concentration (Cmax) of MK-0822 After Single Dose
For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of Cmax.
Time frame: Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose
Population: The per protocol population consisted of all matched participants who complied with the protocol sufficiently to ensure that results will likely exhibit the effects of treatment according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Severe Renal Insufficiency Group | Maximum Concentration (Cmax) of MK-0822 After Single Dose | 359.85 nM |
| Healthy Matched Control Group | Maximum Concentration (Cmax) of MK-0822 After Single Dose | 246.09 nM |
Comparison: Natural log-transformed plasma values were analyzed using an ANCOVA model with a categorical factor for population (severe renal insufficiency participants, healthy matched control participants) and continuous covariates for age and BMI. Data are back transformed to GMR (severe renal insufficiency / healthy) and 90% confidence intervals.90% CI: [1.18, 1.81]
Secondary
Time to Maximum Concentration (Tmax) of MK-0822 After Single Dose
For healthy and severe renal insufficiency participants, plasma samples were collected from predose to 336 hours postdose for determination of Tmax.
Time frame: Pre-dose and 1, 2, 4, 6, 9, 12, 16, 24, 32, 48, 72, 96, 120, 168, 240, and 336 hours postdose
Population: The per protocol population consisted of all matched participants who complied with the protocol sufficiently to ensure that results will likely exhibit the effects of treatment according to the underlying scientific model.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Severe Renal Insufficiency Group | Time to Maximum Concentration (Tmax) of MK-0822 After Single Dose | 18.01 hr |
| Healthy Matched Control Group | Time to Maximum Concentration (Tmax) of MK-0822 After Single Dose | 4.02 hr |