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| ID | Type | Description | Link |
|---|---|---|---|
| MK-0000-386 | Other Identifier | Merck | |
| CA21005 | Other Identifier | Celerion |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| End Stage Renal Disease | Experimental | 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. |
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| Severe Impairment | Experimental | 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. |
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| Moderate Impairment | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam oral solution | Drug | Midazolam hydrochloride 10 μg (1 mL of 10 μg/mL oral solution), administered orally as part of a microdose cocktail |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1 | 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. | 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 |
| Effect of Rifampin on AUC0-inf Post-dose Period 2 | 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. | 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 |
| Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Rifampin on AUC0-24 Post-dose Period 2 | 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. |
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Inclusion Criteria:
All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
Participants with mild, moderate or severe renal impairment or end stage renal disease:
Healthy participants:
Exclusion Criteria:
All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
Participants with mild, moderate or severe renal impairment:
Participants with end stage renal disease (ESRD):
Healthy participants:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Pharmacology of Miami ( Site 0001) | Hialeah | Florida | 33014 | United States | ||
| Orlando Clinical Research Center ( Site 0002) |
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| ID | Title | Description |
|---|---|---|
| FG000 | End-Stage Renal Disease | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 26, 2018 |
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| Mild Impairment | Experimental | 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. |
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| Healthy Control | Active Comparator | 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. |
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| Dabigatran and pitavastatin oral solution | Drug | 375/10 μg dabigatran etexilate and pitavastatin (1 mL of 375/10 μg/mL oral solution), administered orally as part of a microdose cocktail |
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| Atorvastatin and rosuvastatin oral solution | Drug | 100/50 μg atorvastatin and rosuvastatin (2 mL of 50/25 μg/mL oral solution), administered orally as part of a microdose cocktail |
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| Rifampin | Drug | Rifampin 600 mg single dose (two 300 mg capsules) administered orally |
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| 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1 | 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. | 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 |
| Maximum Plasma Concentration (Cmax) Post-dose Period 1 | 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. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
| Plasma Concentration at 24 Hours (C24) Post-dose Period 1 | 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. | 24 hours post-dose |
| Time to Maximum Plasma Concentration (Tmax) Post-dose Period 1 | 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. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
| Apparent Plasma Terminal Half-life (t1/2) Post-dose Period 1 | 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. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
| Apparent Clearance After Extravascular Administration (CL/F) Post-dose Period 1 | 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. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) Post-dose Period 1 | 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. | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
| 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 |
| Effect of Rifampin on AUC0-last Post-dose Period 2 | 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. | 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 |
| Effect of Rifampin on Cmax Post-dose Period 2 | 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. | 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 |
| Effect of Rifampin on C24 Post-dose Period 2 | 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. | 24 hours post-dose |
| Effect of Rifampin on Tmax Post-dose Period 2 | 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. | 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 |
| Effect of Rifampin on t1/2 Post-dose Period 2 | 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. | 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 |
| Effect of Rifampin on CL/F Post-dose Period 2 | 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. | 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 |
| Effect of Rifampin on Vz/F Post-dose Period 2 | 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. | 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 |
| Orlando |
| Florida |
| 32809 |
| United States |
| FG001 | Severe Impairment | 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. |
| FG002 | Moderate Impairment | 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. |
| FG003 | Mild Impairment | 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. |
| FG004 | Healthy Control | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| 14-day Wash-out |
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| Period 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | End-Stage Renal Disease | 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 |
| BG001 | Severe Impairment | 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. |
| BG002 | Moderate Impairment | 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. |
| BG003 | Mild Impairment | 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. |
| BG004 | Healthy Control | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of AUC0-inf for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | pg*hr/mL | 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 |
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| Primary | Effect of Rifampin on AUC0-inf Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of AUC0-inf for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | pg*hr/mL | 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 |
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| Primary | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of AUC0-24 for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | 95% Confidence Interval | pg*hr/mL | 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose |
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| Primary | Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of AUC0-last for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | 95% Confidence Interval | pg*hr/mL | 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 |
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| Primary | Maximum Plasma Concentration (Cmax) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of Cmax for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | 95% Confidence Interval | pg/mL | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
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| Primary | Plasma Concentration at 24 Hours (C24) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of C24 for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | 95% Confidence Interval | pg/mL | 24 hours post-dose |
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| Primary | Time to Maximum Plasma Concentration (Tmax) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of Tmax for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | 95% Confidence Interval | hours | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
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| Primary | Apparent Plasma Terminal Half-life (t1/2) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of t1/2 for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
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| Primary | Apparent Clearance After Extravascular Administration (CL/F) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of CL/F for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters/hour | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
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| Primary | Apparent Volume of Distribution During the Terminal Phase (Vz/F) Post-dose Period 1 | 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. | All participants who were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of Vz/F for the following reasons: non-compliance with the protocol or high pre-dose concentrations. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters | 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose |
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| Secondary | Effect of Rifampin on AUC0-24 Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of AUC0-24 for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | pg*hr/mL | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Effect of Rifampin on AUC0-last Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of AUC0-last for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | pg*hr/mL | 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 |
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| Secondary | Effect of Rifampin on Cmax Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of Cmax for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | pg/mL | 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 |
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| Secondary | Effect of Rifampin on C24 Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of C24 for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | pg/mL | 24 hours post-dose |
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| Secondary | Effect of Rifampin on Tmax Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of Tmax for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Median | Full Range | hours | 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 |
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| Secondary | Effect of Rifampin on t1/2 Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of t1/2 for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | hours | 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 |
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| Secondary | Effect of Rifampin on CL/F Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of CL/F for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | liters/hour | 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 |
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| Secondary | Effect of Rifampin on Vz/F Post-dose Period 2 | 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. | All participants who received rifampin, were compliant with the study procedure and had available data. Per protocol, participants were excluded from this analysis of Vz/F for the following reasons: non-compliance with the protocol or high pre-dose concentrations. Per protocol, end-stage renal disease participants did not receive rifampin. | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | liters | 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 |
|
Up tp approximately 30 days (including 14 days following the last dose)
All participants who received any dose are included. Adverse events were summarized by renal function group assignment and dose received (microdose cocktail alone or microdose cocktail + rifampin).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | End Stage Renal Disease: Microdose Cocktail Alone | 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG001 | Severe Impairment: Microdose Cocktail Alone | Participants with <30 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). | 0 | 7 | 1 | 7 | 2 | 7 |
| EG002 | Severe Impairment: Microdose Cocktail + Rifampin | Participants with <30 mL/min/1.73m^2 eGFR not on hemodialysis. 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | Moderate Impairment: Microdose Cocktail Alone | 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). | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Moderate Impairment: Microdose Cocktail + Rifampin | Moderate ImpairmentEdit Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | Mild Impairment: Microdose Cocktail Alone | 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). | 0 | 7 | 0 | 7 | 3 | 7 |
| EG006 | Mild Impairment: Microdose Cocktail + Rifampin | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG007 | Healthy Control: Microdose Cocktail Alone | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
| EG008 | Healthy Control: Microdose Cocktail + Rifampin | Participants with ≥90 mL/min creatinine clearance. 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. | 0 | 6 | 0 | 6 | 0 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
The Sponsor will provide separate guidance on the criteria for publication of clinical trial data when contacted for permission to publish.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Jul 29, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008874 | Midazolam |
| D000069604 | Dabigatran |
| C108475 | pitavastatin |
| D000069059 | Atorvastatin |
| D000068718 | Rosuvastatin Calcium |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001562 | Benzimidazoles |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Non-Compliance With Study Drug |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Dabigatran |
|
|
| Pitavastatin |
|
|
| Pitavastatin lactone (metabolite) |
|
|
| Atorvastatin |
|
|
| Ortho-hydroxyatorvastatin (metabolite) |
|
|
| Rosuvastatin |
|
|
Comparison of midazolam |
| Geometric least squares mean ratio |
| 1.33 |
| 2-Sided |
| 95 |
| 0.77 |
| 2.31 |
| Other |
Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. |
| Comparison of midazolam | Geometric least squares mean ratio | 0.95 | 2-Sided | 95 | 0.56 | 1.62 | Other | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. |
| Comparison of midazolam | Geometric least squares mean ratio | 0.40 | 2-Sided | 95 | 0.23 | 0.70 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of dabigatran | Geometric least squares mean ratio | 1.01 | 2-Sided | 95 | 0.53 | 1.93 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of dabigatran | Geometric least squares mean ratio | 2.87 | 2-Sided | 95 | 1.51 | 5.47 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of dabigatran | Geometric least squares mean ratio | 4.98 | 2-Sided | 95 | 2.62 | 9.48 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of dabigatran | Geometric least squares mean ratio | 3.39 | 2-Sided | 95 | 1.78 | 6.44 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Geometric least squares mean ratio | 1.32 | 2-Sided | 95 | 0.76 | 2.31 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of pitavastatin |
| Comparison of pitavastatin | Geometric least squares mean ratio | 1.96 | 2-Sided | 95 | 1.12 | 3.42 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of pitavastatin | Geometric least squares mean ratio | 1.25 | 2-Sided | 95 | 0.73 | 2.13 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of pitavastatin | Geometric least squares mean ratio | 1.30 | 2-Sided | 95 | 0.74 | 2.27 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of pitavastatin lactone | Geometric least squares mean ratio | 1.05 | 2-Sided | 95 | 0.64 | 1.72 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Comparison of pitavastatin lactone | Geometric least squares mean ratio | 1.45 | 2-Sided | 95 | 0.88 | 2.38 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Geometric least squares mean ratio | 1.09 | 2-Sided | 95 | 0.68 | 1.76 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of pitavastatin lactone |
| Geometric least squares mean ratio | 0.71 | 2-Sided | 95 | 0.43 | 1.17 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of pitavastatin lactone |
| Geometric least squares mean ratio | 1.13 | 2-Sided | 95 | 0.53 | 2.41 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of atorvastatin |
| Geometric least squares mean ratio | 1.75 | 2-Sided | 95 | 0.89 | 3.46 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of atorvastatin |
| Comparison of atorvastatin | Geometric least squares mean ratio | 1.63 | 2-Sided | 95 | 0.85 | 3.14 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other |
| Geometric least squares mean ratio | 1.13 | 2-Sided | 95 | 0.57 | 2.22 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of atorvastatin |
| Geometric least squares mean ratio | 1.38 | 2-Sided | 95 | 0.76 | 2.49 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of ortho-hydroxyatorvastatin |
| Geometric least squares mean ratio | 1.31 | 2-Sided | 95 | 0.75 | 2.29 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of ortho-hydroxyatorvastatin |
| Geometric least squares mean ratio | 1.09 | 2-Sided | 95 | 0.65 | 1.81 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of ortho-hydroxyatorvastatin |
| Geometric least squares mean ratio | 0.79 | 2-Sided | 95 | 0.46 | 1.33 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of ortho-hydroxyatorvastatin |
| Geometric least squares mean ratio | 0.90 | 2-Sided | 95 | 0.33 | 2.45 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of rosuvastatin |
| Geometric least squares mean ratio | 1.97 | 2-Sided | 95 | 0.75 | 5.14 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of rosuvastatin |
| Geometric least squares mean ratio | 1.25 | 2-Sided | 95 | 0.49 | 3.16 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of rosuvastatin |
| Geometric least squares mean ratio | 0.71 | 2-Sided | 95 | 0.27 | 1.86 | Geometric least squares mean ratio and 95% confidence interval could not be determined for comparisons where one or both of the geometric least squares means was not calculable because some individual values were treated as 0. | Other | Comparison of rosuvastatin |
| OG001 | Severe Impairment (Period 2) | Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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| Severe Impairment |
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. |
| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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| OG001 |
| Severe Impairment |
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. |
| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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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.
| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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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. |
| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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| Severe Impairment |
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. |
| OG002 | Moderate Impairment | 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. |
| OG003 | Mild Impairment | 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. |
| OG004 | Healthy Control | 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. |
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| OG001 | Severe Impairment (Period 2) | Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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| OG001 | Severe Impairment (Period 2) | Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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| Severe Impairment (Period 2) |
Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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| Severe Impairment (Period 2) |
Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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| OG001 |
| Severe Impairment (Period 2) |
Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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| Severe Impairment (Period 2) |
Participants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. 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. |
| OG002 | Moderate Impairment (Period 2) | Participants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG003 | Mild Impairment (Period 2) | Participants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. 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. |
| OG004 | Healthy Control (Period 2) | Participants with ≥90 mL/min creatinine clearance. 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. |
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