Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin in Participants With Renal Insufficiency in the Presence and Absence of Rifampin (MK-0000-386)
- Conditions
- Renal Insufficiency
- Interventions
- Registration Number
- NCT03311841
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this open-label, 2-period, fixed-sequence study is to characterize the plasma pharmacokinetic profiles of midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin following a single oral dose administration of a microdose cocktail in healthy participants, in participants with mild, moderate, severe (not on dialysis) renal impairment, and in participants with end-stage renal disease (ESRD; on dialysis).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
- a female must be non-pregnant, non-breast feeding and if she is of reproductive potential: must agree to use (and/or have their partner use) two acceptable methods of birth control beginning at screening, throughout the study and until 2 weeks after the last dosing of study drug
- a female of non-childbearing potential: must have undergone a sterilization procedure at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at least 1 year prior to the first dose
- a non-vasectomized male participant must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after the last dose of study drug
- a male participant must agree not to donate sperm from dosing until 90 days after the last dose of study drug
- has a body mass index (BMI) ≤ 40.0 kg/m^2
- is a non-smoker or moderate smoker (≤ 20 cigarettes/day or the equivalent)
Participants with mild, moderate or severe renal impairment or end stage renal disease:
- has a clinical diagnosis of renal impairment and meets the protocol-specified renal impairment function qualifications at the prestudy visit (screening)
Healthy participants:
- has baseline creatinine clearance ≥ 90 mL/min based on Cockcroft-Gault equation
- is judged to be in good health based on medical history, physical examination, vital signs, pulse oximetry, and laboratory safety tests
All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
- is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- history or presence of clinically significant medical or psychiatric condition or disease
- history of stroke, chronic seizures, or major neurological disorders
- history of malignant neoplastic disease
- history or presence of alcoholism or drug abuse within the past 6 months
- female participant who is pregnant or lactating
Participants with mild, moderate or severe renal impairment:
- has had a renal transplant or has had nephrectomy
- has uncontrolled type 2 diabetes mellitus (T2DM), a history of Type 1 diabetes, or ketoacidosis
- history of significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
Participants with end stage renal disease (ESRD):
- had a failed renal allograft within the last 2 years prior to the first dose, or a successful renal allograft
- has uncontrolled T2DM, a history of Type 1 diabetes, or ketoacidosis
- history of significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
Healthy participants:
- history of hypoglycemia, glucose intolerance, T2DM, or ketoacidosis
- history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description End Stage Renal Disease Midazolam oral solution Participants requiring hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). A washout period of at least 14 days will separate dosings. End Stage Renal Disease Atorvastatin and rosuvastatin oral solution Participants requiring hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). A washout period of at least 14 days will separate dosings. Moderate Impairment Midazolam oral solution Participants with 30 to \<60 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Moderate Impairment Atorvastatin and rosuvastatin oral solution Participants with 30 to \<60 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Healthy Control Midazolam oral solution Participants with ≥90 mL/min creatinine clearance. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Healthy Control Atorvastatin and rosuvastatin oral solution Participants with ≥90 mL/min creatinine clearance. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Severe Impairment Dabigatran and pitavastatin oral solution Participants with \<30 mL/min/1.73m\^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Severe Impairment Atorvastatin and rosuvastatin oral solution Participants with \<30 mL/min/1.73m\^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Moderate Impairment Dabigatran and pitavastatin oral solution Participants with 30 to \<60 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. End Stage Renal Disease Dabigatran and pitavastatin oral solution Participants requiring hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). A washout period of at least 14 days will separate dosings. Severe Impairment Midazolam oral solution Participants with \<30 mL/min/1.73m\^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Mild Impairment Dabigatran and pitavastatin oral solution Participants with 60 to \<90 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Healthy Control Dabigatran and pitavastatin oral solution Participants with ≥90 mL/min creatinine clearance. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Mild Impairment Midazolam oral solution Participants with 60 to \<90 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Mild Impairment Atorvastatin and rosuvastatin oral solution Participants with 60 to \<90 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Severe Impairment Rifampin Participants with \<30 mL/min/1.73m\^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Moderate Impairment Rifampin Participants with 30 to \<60 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Mild Impairment Rifampin Participants with 60 to \<90 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings. Healthy Control Rifampin Participants with ≥90 mL/min creatinine clearance. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post-dose. This is a measure of the average amount of study drug in the blood plasma over a period of 24 hours after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Time to Maximum Plasma Concentration (Tmax) Post-dose Period 1 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose Tmax is the amount of time to reach maximum (peak) plasma drug concentration following drug administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Apparent Clearance After Extravascular Administration (CL/F) Post-dose Period 1 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose CL/F is the rate at which study drug was removed from the body. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. CL/F was to be calculated for the parent plasma analytes only, midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin.
Apparent Volume of Distribution During the Terminal Phase (Vz/F) Post-dose Period 1 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose Vz/F is the distribution of study drug between the plasma and the rest of the body after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. Vz/F was to be calculated for the parent plasma analytes only, midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin.
Effect of Rifampin on AUC0-inf Post-dose Period 2 Microdose cocktail: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0 hour (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the AUC0-inf of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include data from the end-stage renal disease participants as they did not receive rifampin during Period 2.
Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. This is a measure of the amount of study drug in the blood plasma from pre-dose until the last measurable concentration of study drug could be determined. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Plasma Concentration at 24 Hours (C24) Post-dose Period 1 24 hours post-dose C24hr is a measure of the plasma study drug concentration 24 hours post-dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Apparent Plasma Terminal Half-life (t1/2) Post-dose Period 1 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose T1/2 is the elimination half-life of study drug. T1/2 is the time it takes for half of the study drug in the blood plasma to dissipate. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease (ESRD) requiring hemodialysis.
Maximum Plasma Concentration (Cmax) Post-dose Period 1 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose Cmax is the peak plasma concentration of study drug after administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
- Secondary Outcome Measures
Name Time Method Effect of Rifampin on AUC0-24 Post-dose Period 2 Microdose cocktail: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose; rifampin: 0 hour (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the AUC0-24 of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post-dose. This is a measure of the average amount of study drug in the blood plasma over a period of 24 hours after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on C24 Post-dose Period 2 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the C24 of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. C24 is a measure of the plasma study drug concentration 24 hours post-dose. C24 is reported as median (minimum and maximum) in severe renal impairment arm due to zero values. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on Tmax Post-dose Period 2 Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the Tmax of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. Tmax is the amount of time to reach maximum (peak) plasma drug concentration following drug administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on AUC0-last Post-dose Period 2 Microdose cocktail: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0 hour (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the AUC0-last of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. It is a measure of the amount of study drug in the blood plasma from pre-dose until the last measurable concentration of study drug could be determined. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on t1/2 Post-dose Period 2 Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the t1/2 of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. T1/2 is the elimination half-life of study drug. T1/2 is the time it takes for half of the study drug in the blood plasma to dissipate. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on Cmax Post-dose Period 2 Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the Cmax of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. Cmax is the peak plasma concentration of study drug after administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on CL/F Post-dose Period 2 Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the CL/F of midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvatatin. CL/F is the rate at which study drug was removed from the body. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Effect of Rifampin on Vz/F Post-dose Period 2 Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose To evaluate the effect of a single oral dose of rifampin on the Vz/F of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. Vz/F is the distribution of study drug between the plasma and the rest of the body after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2.
Trial Locations
- Locations (2)
Clinical Pharmacology of Miami ( Site 0001)
🇺🇸Hialeah, Florida, United States
Orlando Clinical Research Center ( Site 0002)
🇺🇸Orlando, Florida, United States