A Phase 1 interventional study of Midazolam oral solution and Dabigatran and pitavastatin oral solution in Renal Insufficiency, sponsored by Merck Sharp & Dohme LLC. Completed at 2 sites in United States. Open to participants aged 18 Years to 78 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-01-09.
Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 1, Interventional, and Treatment
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
Among 32 studies in Renal Insufficiency by Merck & Co., Inc — 2 open to participants now, 2 under way, none of them phase 3. Renal Insufficiency · Merck & Co., Inc.
Among the 32 studies in Renal Insufficiency by Merck & Co., Inc, this one is the 12th largest by enrollment, is the only one that started in 2018, is one of 25 in phase 1, and was the 23rd registered.
1,412 studies on the registry are indexed under Renal Insufficiency; 145 are open to participants now.
Browse Renal Insufficiency studies →2 of the 32 studies in Renal Insufficiency by Merck & Co., Inc are open now, in 1 country. Recruiting first, the newest first:
Merck Sharp & Dohme LLC · Sites in United States
Ages 18–80 · Healthy volunteers
Merck Sharp & Dohme LLC
Ages 18–80 · Healthy volunteers
By country, each count listing its studies:
Of the 91 Renal Insufficiency studies recruiting now, 48 (53%) set no upper age limit and 18 (20%) stop at 75 or younger; 8 take children under 18; 15 take healthy volunteers.
This study: 18 Years to 78 Years · all sexes · healthy volunteers too.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
32 studies; the count open now beside each. This study's row is marked.
First in 2003; this study’s year is marked. 1 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 32 is below the median of 40 across 1,060 interventional studies indexed under Renal Insufficiency.
Median enrollment 26 across the 32 interventional studies. Of the 29 that completed or were terminated, 17 (59%) have results posted.
This tab as a report to print or save as PDF → With an account.
This study is registered under Merck Sharp & Dohme LLC, one of the names counted as Merck & Co., Inc. Under that name alone:
Merck Sharp & Dohme LLC is the lead sponsor of 2,166 studies on the registry; 131 are open to participants now.
Of its 503 completed or terminated interventional studies of FDA-regulated products, 371 (74%) have results posted.
2 of the studies in Renal Insufficiency by Merck & Co., Inc that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07734610Merck Sharp & Dohme LLCA Clinical Trial of Nemtabrutinib in Participants With Severe Kidney Disease (MK-1026-027) | 2027-02-01 |
| NCT07922174Merck Sharp & Dohme LLCA Clinical Trial of MK-6916 in Participants With Moderate and Severe Kidney Disease Compared to Healthy Controls (MK-6916-013) | 2027-08-06 |
Add all 2 to your calendar (.ics) → With an account.
Among the 32 studies in Renal Insufficiency by Merck & Co., Inc, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Midazolam oral solution · Drug: Dabigatran and pitavastatin oral solution · Drug: Atorvastatin and rosuvastatin oral solution
Participants with \<30 mL/min/1.73m\^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Drug: Midazolam oral solution · Drug: Dabigatran and pitavastatin oral solution · Drug: Atorvastatin and rosuvastatin oral solution · Drug: Rifampin
Participants with 30 to \<60 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Drug: Midazolam oral solution · Drug: Dabigatran and pitavastatin oral solution · Drug: Atorvastatin and rosuvastatin oral solution · Drug: Rifampin
Participants with 60 to \<90 mL/min/1.73m\^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Drug: Midazolam oral solution · Drug: Dabigatran and pitavastatin oral solution · Drug: Atorvastatin and rosuvastatin oral solution · Drug: Rifampin
Participants with ≥90 mL/min creatinine clearance. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Drug: Midazolam oral solution · Drug: Dabigatran and pitavastatin oral solution · Drug: Atorvastatin and rosuvastatin oral solution · Drug: Rifampin
Midazolam hydrochloride 10 μg (1 mL of 10 μg/mL oral solution), administered orally as part of a microdose cocktail
Drug pages: Dabigatran · Pitavastatin
375/10 μg dabigatran etexilate and pitavastatin (1 mL of 375/10 μg/mL oral solution), administered orally as part of a microdose cocktail
Drug pages: Atorvastatin · Rosuvastatin
100/50 μg atorvastatin and rosuvastatin (2 mL of 50/25 μg/mL oral solution), administered orally as part of a microdose cocktail
Rifampin 600 mg single dose (two 300 mg capsules) administered orally
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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 AUC0-24 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
| Milestone | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Started | 6 | 7 | 6 | 7 | 6 |
| Completed | 6 | 7 | 6 | 7 | 6 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
| Milestone | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Started | 6 | 7 | 6 | 7 | 6 |
| Completed | 6 | 6 | 6 | 6 | 6 |
| Not completed | 0 | 1 | 0 | 1 | 0 |
| Withdrew: Adverse event | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Non-compliance with study drug | 0 | 0 | 0 | 1 | 0 |
| Milestone | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Started | 6 | 6 | 6 | 6 | 6 |
| Completed | 6 | 6 | 6 | 6 | 6 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
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.
| pg*hr/mL | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 110 (74.6 to 162) | 260 (181 to 372) | 364 (247 to 537) | 176 (119 to 259) | 273 (185 to 403) |
| Dabigatran | 5370 (3410 to 8460) | 7900 (5010 to 12400) | 4550 (2890 to 7180) | 1610 (1020 to 2530) | 1580 (1010 to 2500) |
| Pitavastatin | 676 (456 to 1000) | 648 (450 to 933) | 1020 (686 to 1510) | 688 (464 to 1020) | 520 (350 to 771) |
| Pitavastatin lactone (metabolite) | 1100 (774 to 1560) | 1680 (1220 to 2320) | 2240 (1580 to 3170) | 1610 (1140 to 2290) | 1540 (1090 to 2190) |
| Atorvastatin | 329 (203 to 531) | 476 (305 to 743) | 511 (316 to 826) | 329 (183 to 593) | 292 (180 to 472) |
| Ortho-hydroxyatorvastatin (metabolite) | 163 (112 to 237) | 226 (160 to 319) | 273 (181 to 411) | 286 (181 to 453) | 208 (143 to 302) |
| Rosuvastatin | 208 (116 to 374) | 365 (213 to 624) | 575 (319 to 1030) | 262 (136 to 505) | 292 (137 to 624) |
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.
| pg*hr/mL | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 244 (175 to 340) | 359 (252 to 512) | 189 (132 to 269) | 239 (168 to 341) |
| Dabigatran | — | 10700 (7390 to 15600) | 7240 (4990 to 10500) | 3040 (2090 to 4400) | 3290 (2270 to 4770) |
| Pitavastatin | — | 2850 (1840 to 4440) | 3500 (2200 to 5570) | 2530 (1590 to 4030) | 1910 (1200 to 3030) |
| Pitavastatin lactone (metabolite) | — | 1560 (1160 to 2100) | 2500 (1830 to 3430) | 1930 (1410 to 2640) | 1340 (981 to 1840) |
| Atorvastatin | — | 2240 (1520 to 3320) | 2430 (1620 to 3650) | 1710 (1040 to 2810) | 1770 (1180 to 2660) |
| Ortho-hydroxyatorvastatin (metabolite) | — | 1620 (1080 to 2430) | 1870 (1230 to 2840) | 1760 (1060 to 2940) | 1650 (1080 to 2500) |
| Rosuvastatin | — | 1240 (839 to 1830) | 1800 (1150 to 2820) | 1060 (695 to 1620) | 830 (553 to 1250) |
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.
| pg*hr/mL | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 106 (74.2 to 152) | 235 (169 to 328) | 317 (222 to 454) | 168 (117 to 240) | 252 (176 to 360) |
| Dabigatran | 2100 (1380 to 3200) | 4470 (3030 to 6590) | 3440 (2260 to 5240) | 1380 (907 to 2100) | 1440 (949 to 2200) |
| Pitavastatin | 593 (411 to 857) | 525 (374 to 738) | 764 (529 to 1100) | 543 (376 to 783) | 415 (288 to 600) |
| Pitavastatin lactone (metabolite) | 858 (639 to 1150) | 1100 (835 to 1440) | 1280 (950 to 1710) | 1040 (772 to 1390) | 1010 (750 to 1350) |
| Atorvastatin | 287 (184 to 446) | 300 (199 to 452) | 329 (211 to 512) | 219 (128 to 377) | 198 (127 to 308) |
| Ortho-hydroxyatorvastatin (metabolite) | 115 (78.3 to 168) | 112 (78.5 to 159) | 143 (98.0 to 210) | 139 (86.9 to 221) | 108 (73.8 to 158) |
| Rosuvastatin | 162 (97.2 to 271) | 223 (139 to 358) | 343 (206 to 573) | 191 (109 to 334) | 153 (91.6 to 255) |
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.
| pg*hr/mL | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 105 (70.8 to 156) | 248 (172 to 358) | 344 (232 to 511) | 167 (113 to 248) | 264 (178 to 392) |
| Dabigatran | 3740 (2370 to 5910) | 7450 (4870 to 11400) | 4230 (2680 to 6690) | 1440 (910 to 2270) | 1410 (891 to 2230) |
| Pitavastatin | 649 (435 to 968) | 602 (416 to 871) | 950 (637 to 1420) | 643 (431 to 959) | 483 (324 to 721) |
| Pitavastatin lactone (metabolite) | 1060 (754 to 1480) | 1570 (1150 to 2140) | 2020 (1440 to 2830) | 1490 (1060 to 2080) | 1450 (1030 to 2030) |
| Atorvastatin | 298 (182 to 488) | 419 (266 to 662) | 459 (280 to 751) | 295 (161 to 539) | 255 (155 to 417) |
| Ortho-hydroxyatorvastatin (metabolite) | 126 (80.3 to 198) | 176 (116 to 267) | 256 (163 to 402) | 221 (127 to 385) | 152 (96.8 to 239) |
| Rosuvastatin | 171 (98.0 to 298) | 269 (161 to 451) | 479 (274 to 835) | 231 (125 to 424) | 181 (104 to 315) |
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.
| pg/mL | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 39.9 (29.5 to 53.9) | 68.4 (51.8 to 90.4) | 77.2 (57.1 to 104) | 70.7 (52.3 to 95.5) | 73.2 (54.1 to 98.8) |
| Dabigatran | 132 (83.1 to 208) | 319 (209 to 489) | 312 (197 to 494) | 153 (96.9 to 243) | 183 (115 to 290) |
| Pitavastatin | 242 (173 to 339) | 218 (160 to 299) | 303 (216 to 425) | 244 (174 to 342) | 164 (117 to 230) |
| Pitavastatin lactone (metabolite) | 78.5 (59.8 to 103) | 95.4 (74.2 to 123) | 106 (80.6 to 139) | 105 (79.9 to 137) | 88.1 (67.1 to 116) |
| Atorvastatin | 63.7 (35.3 to 115) | 46.7 (27.1 to 80.5) | 55.0 (30.5 to 99.1) | 31.9 (15.5 to 65.7) | 21.6 (12.0 to 38.9) |
| Ortho-hydroxyatorvastatin (metabolite) | 8.58 (5.77 to 12.8) | 7.22 (5.00 to 10.4) | 9.50 (6.39 to 14.1) | 8.50 (5.23 to 13.8) | 7.67 (5.16 to 11.4) |
| Rosuvastatin | 22.5 (12.4 to 40.6) | 24.4 (14.1 to 42.1) | 40.4 (22.4 to 72.9) | 23.6 (12.4 to 45.1) | 21.5 (11.9 to 38.9) |
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.
| pg/mL | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 0.283 (0.00 to 0.928) | 1.83 (0.00 to 8.47) | 2.64 (1.54 to 4.54) | 0.734 (0.00 to 1.06) | 1.57 (0.914 to 2.70) |
| Dabigatran | 70.2 (45.3 to 109) | 107 (71.7 to 161) | 59.3 (38.3 to 91.8) | 18.7 (12.1 to 28.9) | 7.70 (0.00 to 26.6) |
| Pitavastatin | 6.07 (0.00 to 7.99) | 4.04 (2.83 to 5.76) | 8.13 (5.53 to 11.9) | 5.32 (3.62 to 7.82) | 4.10 (2.79 to 6.03) |
| Pitavastatin lactone (metabolite) | 12.9 (8.01 to 20.9) | 23.2 (14.9 to 36.2) | 32.8 (20.3 to 52.9) | 22.4 (13.9 to 36.2) | 21.7 (13.5 to 35.0) |
| Atorvastatin | 4.28 (0.00 to 6.63) | 5.73 (3.80 to 8.64) | 6.03 (3.86 to 9.40) | 5.04 (2.73 to 5.89) | 3.85 (2.47 to 6.00) |
| Ortho-hydroxyatorvastatin (metabolite) | 3.67 (0.00 to 4.64) | 3.25 (2.29 to 4.63) | 4.43 (3.03 to 6.49) | 5.02 (2.26 to 9.31) | 3.08 (2.10 to 4.51) |
| Rosuvastatin | 2.64 (0.00 to 4.36) | 3.40 (2.24 to 5.16) | 6.01 (3.83 to 9.43) | 3.59 (2.19 to 5.88) | 1.94 (1.24 to 3.05) |
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.
| hours | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 0.50 (0.50 to 1.00) | 0.50 (0.50 to 1.00) | 0.50 (0.50 to 1.00) | 0.50 (0.50 to 1.00) | 1.00 (0.50 to 1.00) |
| Dabigatran | 2.00 (1.00 to 4.00) | 3.00 (2.00 to 4.00) | 2.50 (2.00 to 3.00) | 1.50 (1.50 to 3.00) | 1.50 (1.50 to 3.00) |
| Pitavastatin | 0.50 (0.50 to 1.00) | 0.50 (0.50 to 1.50) | 1.00 (0.50 to 1.00) | 0.52 (0.50 to 1.00) | 0.75 (0.50 to 1.00) |
| Pitavastatin lactone (metabolite) | 2.50 (2.00 to 6.33) | 4.00 (2.00 to 4.00) | 2.50 (2.00 to 3.00) | 2.00 (1.50 to 2.00) | 2.00 (2.00 to 3.00) |
| Atorvastatin | 0.25 (0.25 to 0.50) | 0.25 (0.25 to 6.00) | 0.25 (0.25 to 1.50) | 0.25 (0.25 to 0.53) | 0.50 (0.50 to 6.00) |
| Ortho-hydroxyatorvastatin (metabolite) | 5.00 (4.00 to 6.00) | 6.00 (4.00 to 8.00) | 6.00 (4.00 to 8.00) | 6.00 (6.00 to 8.00) | 6.00 (3.00 to 6.00) |
| Rosuvastatin | 3.00 (1.50 to 4.00) | 4.00 (3.00 to 4.00) | 4.00 (1.50 to 4.02) | 2.00 (2.00 to 4.00) | 3.50 (0.50 to 4.00) |
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.
| hours | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 4.41 ± 59.6 | 7.79 ± 54.1 | 10.3 ± 33.0 | 6.76 ± 30.6 | 7.99 ± 25.0 |
| Dabigatran | 41.4 ± 47.9 | 24.0 ± 22.0 | 11.9 ± 30.3 | 8.40 ± 10.7 | 6.75 ± 19.8 |
| Pitavastatin | 11.8 ± 61.4 | 20.4 ± 63.6 | 22.4 ± 15.8 | 19.3 ± 23.5 | 17.8 ± 26.7 |
| Pitavastatin lactone (metabolite) | 11.0 ± 55.3 | 18.1 ± 31.0 | 22.0 ± 13.2 | 20.5 ± 31.4 | 18.5 ± 15.9 |
| Atorvastatin | 8.03 ± 28.5 | 17.5 ± 57.0 | 18.6 ± 41.8 | 16.7 ± 14.8 | 14.9 ± 10.3 |
| Ortho-hydroxyatorvastatin (metabolite) | 12.4 ± 25.8 | 21.9 ± 65.9 | 24.6 ± 18.3 | 22.8 ± 35.7 | 21.2 ± 29.5 |
| Rosuvastatin | 14.0 ± 107.3 | 18.8 ± 78.3 | 24.9 ± 19.4 | 15.5 ± 100.2 | 16.2 ± 78.6 |
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.
| liters/hour | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 90.8 ± 46.5 | 38.5 ± 62.7 | 27.5 ± 46.3 | 56.9 ± 32.3 | 36.6 ± 50.6 |
| Dabigatran | 52.5 ± 74.1 | 35.7 ± 32.3 | 61.8 ± 70.3 | 175 ± 47.3 | 178 ± 61.5 |
| Pitavastatin | 14.8 ± 60.0 | 15.4 ± 58.6 | 9.84 ± 29.7 | 14.5 ± 41.1 | 19.2 ± 52.7 |
| Atorvastatin | 304 ± 64.7 | 210 ± 82.9 | 196 ± 54.0 | 304 ± 28.7 | 343 ± 56.9 |
| Rosuvastatin | 240 ± 121.0 | 137 ± 49.0 | 87.0 ± 32.3 | 191 ± 82.5 | 171 ± 47.8 |
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.
| liters | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control |
|---|---|---|---|---|---|
| Midazolam | 579 ± 45.0 | 433 ± 16.9 | 409 ± 38.0 | 555 ± 58.0 | 422 ± 37.5 |
| Dabigatran | 3140 ± 38.4 | 1230 ± 36.4 | 1060 ± 54.1 | 2120 ± 57.9 | 1730 ± 46.4 |
| Pitavastatin | 252 ± 19.5 | 454 ± 51.9 | 317 ± 15.4 | 405 ± 46.8 | 495 ± 46.6 |
| Atorvastatin | 3520 ± 40.3 | 5310 ± 47.7 | 5240 ± 57.5 | 7300 ± 32.5 | 7380 ± 58.6 |
| Rosuvastatin | 4870 ± 63.2 | 3720 ± 51.3 | 3120 ± 35.9 | 4270 ± 117.9 | 4010 ± 34.4 |
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.
| pg*hr/mL | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 238 (171 to 330) | 346 (224 to 490) | 186 (131 to 263) | 234 (165 to 332) |
| Dabigatran | — | 6540 (4730 to 9030) | 5480 (3900 to 7700) | 2660 (1890 to 3740) | 3030 (2160 to 4260) |
| Pitavastatin | — | 2760 (1780 to 4270) | 3360 (2120 to 5330) | 2460 (1550 to 3900) | 1860 (1170 to 2950) |
| Pitavastatin lactone (metabolite) | — | 1070 (820 to 1400) | 1780 (1340 to 2350) | 1490 (1120 to 1970) | 1000 (755 to 1320) |
| Atorvastatin | — | 2230 (1510 to 3290) | 2420 (1610 to 3630) | 1700 (1030 to 2790) | 1760 (1180 to 2650) |
| Ortho-hydroxyatorvastatin (metabolite) | — | 1580 (1060 to 2350) | 1800 (1190 to 2730) | 1720 (1030 to 2870) | 1620 (1070 to 2460) |
| Rosuvastatin | — | 1100 (779 to 1550) | 1670 (1170 to 2400) | 1010 (682 to 1500) | 842 (588 to 1210) |
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.
| pg*hr/mL | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 236 (168 to 331) | 353 (246 to 505) | 182 (127 to 261) | 231 (161 to 331) |
| Dabigatran | — | 10400 (7310 to 14800) | 6830 (4710 to 9920) | 2830 (1950 to 4110) | 3140 (2160 to 4550) |
| Pitavastatin | — | 2850 (1830 to 4430) | 3480 (2180 to 5540) | 2510 (1580 to 4000) | 1890 (1190 to 3010) |
| Pitavastatin lactone (metabolite) | — | 1470 (1100 to 1980) | 2380 (1750 to 3250) | 1850 (1350 to 2520) | 1270 (935 to 1740) |
| Atorvastatin | — | 2220 (1490 to 3290) | 2420 (1600 to 3650) | 1690 (1020 to 2800) | 1760 (1160 to 2650) |
| Ortho-hydroxyatorvastatin (metabolite) | — | 1610 (1080 to 2400) | 1850 (1220 to 2820) | 1750 (1050 to 2920) | 1630 (1070 to 2470) |
| Rosuvastatin | — | 1150 (806 to 1630) | 1740 (1200 to 2500) | 1040 (698 to 1560) | 854 (592 to 1230) |
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.
| pg/mL | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 75.4 (57.1 to 99.7) | 92.5 (69.0 to 124) | 73.0 (54.5 to 97.9) | 81.4 (60.7 to 109) |
| Dabigatran | — | 422 (305 to 584) | 443 (314 to 624) | 243 (173 to 342) | 351 (249 to 494) |
| Pitavastatin | — | 981 (591 to 1630) | 860 (509 to 1450) | 819 (485 to 1380) | 599 (354 to 1010) |
| Pitavastatin lactone (metabolite) | — | 88.4 (72.8 to 107) | 119 (97.3 to 145) | 131 (108 to 161) | 102 (83.7 to 125) |
| Atorvastatin | — | 531 (354 to 796) | 508 (337 to 766) | 505 (305 to 835) | 405 (269 to 611) |
| Ortho-hydroxyatorvastatin (metabolite) | — | 150 (97.1 to 231) | 174 (111 to 272) | 215 (124 to 372) | 198 (126 to 310) |
| Rosuvastatin | — | 208 (133 to 327) | 396 (248 to 633) | 254 (152 to 425) | 236 (148 to 376) |
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.
| pg/mL | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 0.394 (0.00 to 4.15) | 1.42 (0.701 to 2.89) | 0.00 (0.00 to 0.921) | 0.601 (0.00 to 1.33) |
| Dabigatran | — | 174 (115 to 263) | 100 (65.1 to 154) | 31.1 (20.2 to 47.9) | 27.5 (17.9 to 42.4) |
| Pitavastatin | — | 7.01 (3.81 to 12.9) | 10.5 (5.54 to 19.8) | 4.70 (2.49 to 8.87) | 4.72 (2.50 to 8.91) |
| Pitavastatin lactone (metabolite) | — | 21.3 (15.0 to 30.3) | 34.0 (23.5 to 49.3) | 20.7 (14.3 to 30.0) | 17.1 (11.8 to 24.8) |
| Atorvastatin | — | 2.98 (0.00 to 16.1) | 2.98 (1.65 to 5.40) | 1.76 (0.00 to 2.32) | 1.35 (0.00 to 3.20) |
| Ortho-hydroxyatorvastatin (metabolite) | — | 7.23 (3.70 to 14.1) | 9.96 (5.02 to 19.8) | 6.28 (2.71 to 14.5) | 5.57 (2.81 to 11.1) |
| Rosuvastatin | — | 4.47 (2.34 to 8.53) | 6.97 (3.53 to 13.8) | 4.18 (1.22 to 9.99) | 2.42 (0.00 to 6.92) |
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.
| hours | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 0.50 (0.50 to 1.00) | 0.75 (0.50 to 1.00) | 0.50 (0.50 to 1.00) | 1.00 (0.50 to 1.00) |
| Dabigatran | — | 3.50 (2.00 to 4.05) | 3.00 (2.00 to 4.00) | 2.50 (2.00 to 4.00) | 2.50 (1.50 to 3.00) |
| Pitavastatin | — | 1.00 (0.50 to 1.00) | 1.00 (0.50 to 2.00) | 1.00 (0.50 to 3.00) | 1.00 (1.00 to 2.00) |
| Pitavastatin lactone (metabolite) | — | 3.00 (1.50 to 4.00) | 4.00 (2.00 to 12.00) | 3.00 (1.50 to 4.00) | 2.00 (1.50 to 4.05) |
| Atorvastatin | — | 0.50 (0.50 to 1.00) | 1.50 (0.50 to 2.00) | 1.00 (1.00 to 1.50) | 1.50 (1.00 to 2.00) |
| Ortho-hydroxyatorvastatin (metabolite) | — | 1.75 (1.00 to 4.05) | 2.50 (1.50 to 4.00) | 1.75 (1.00 to 4.00) | 3.00 (1.00 to 4.05) |
| Rosuvastatin | — | 1.00 (1.00 to 2.00) | 2.00 (1.00 to 3.00) | 1.00 (1.00 to 3.00) | 2.00 (1.00 to 6.00) |
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.
| hours | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 4.14 ± 19.5 | 5.49 ± 26.2 | 4.12 ± 26.7 | 4.97 ± 22.0 |
| Dabigatran | — | 19.4 ± 21.3 | 11.3 ± 33.1 | 7.57 ± 19.0 | 6.48 ± 13.7 |
| Pitavastatin | — | 6.99 ± 62.8 | 11.5 ± 71.6 | 8.40 ± 75.8 | 6.50 ± 30.3 |
| Pitavastatin lactone (metabolite) | — | 17.2 ± 41.0 | 17.7 ± 25.2 | 21.0 ± 22.5 | 16.5 ± 33.9 |
| Atorvastatin | — | 3.14 ± 18.9 | 2.99 ± 21.1 | 3.22 ± 8.6 | 2.76 ± 8.4 |
| Ortho-hydroxyatorvastatin (metabolite) | — | 4.56 ± 43.7 | 4.25 ± 39.7 | 3.83 ± 19.7 | 3.49 ± 11.7 |
| Rosuvastatin | — | 4.89 ± 49.9 | 7.48 ± 19.8 | 9.64 ± 83.8 | 6.76 ± 94.3 |
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.
| liters/hour | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 40.5 ± 57.7 | 27.8 ± 52.0 | 53.0 ± 34.8 | 41.8 ± 28.4 |
| Dabigatran | — | 26.3 ± 41.6 | 38.9 ± 58.7 | 92.8 ± 41.5 | 85.6 ± 40.0 |
| Pitavastatin | — | 3.57 ± 50.0 | 2.86 ± 60.4 | 3.95 ± 51.8 | 5.24 ± 75.8 |
| Atorvastatin | — | 44.2 ± 57.6 | 41.1 ± 30.3 | 58.6 ± 49.4 | 56.4 ± 62.2 |
| Rosuvastatin | — | 38.6 ± 37.7 | 28.9 ± 41.1 | 47.1 ± 51.1 | 57.9 ± 63.3 |
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.
| liters | End Stage Renal Disease (Period 2) | Severe Impairment (Period 2) | Moderate Impairment (Period 2) | Mild Impairment (Period 2) | Healthy Control (Period 2) |
|---|---|---|---|---|---|
| Midazolam | — | 242 ± 44.6 | 220 ± 56.5 | 315 ± 30.8 | 300 ± 36.3 |
| Dabigatran | — | 733 ± 29.2 | 632 ± 36.3 | 1010 ± 45.2 | 800 ± 41.1 |
| Pitavastatin | — | 36.0 ± 38.7 | 47.3 ± 85.8 | 47.8 ± 82.5 | 49.2 ± 72.1 |
| Atorvastatin | — | 200 ± 55.4 | 177 ± 38.2 | 272 ± 58.4 | 225 ± 68.7 |
| Rosuvastatin | — | 272 ± 39.7 | 313 ± 58.2 | 654 ± 40.8 | 565 ± 76.1 |
Collected over Up tp approximately 30 days (including 14 days following the last dose). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| End Stage Renal Disease: Microdose Cocktail Alone | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) |
| Severe Impairment: Microdose Cocktail Alone | 0/7 (0%) | 1/7 (14.3%) | 2/7 (28.6%) |
| Severe Impairment: Microdose Cocktail + Rifampin | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) |
| Moderate Impairment: Microdose Cocktail Alone | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Moderate Impairment: Microdose Cocktail + Rifampin | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) |
| Mild Impairment: Microdose Cocktail Alone | 0/7 (0%) | 0/7 (0%) | 3/7 (42.9%) |
| Mild Impairment: Microdose Cocktail + Rifampin | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Healthy Control: Microdose Cocktail Alone | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) |
| Healthy Control: Microdose Cocktail + Rifampin | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) |
| Event | End Stage Renal Disease: Microdose Cocktail Alone | Severe Impairment: Microdose Cocktail Alone | Severe Impairment: Microdose Cocktail + Rifampin | Moderate Impairment: Microdose Cocktail Alone | Moderate Impairment: Microdose Cocktail + Rifampin | Mild Impairment: Microdose Cocktail Alone | Mild Impairment: Microdose Cocktail + Rifampin | Healthy Control: Microdose Cocktail Alone | Healthy Control: Microdose Cocktail + Rifampin |
|---|---|---|---|---|---|---|---|---|---|
| Cardiac failure congestiveCardiac disorders | 0/6 | 1/7 | 0/6 | 0/6 | 0/6 | 0/7 | 0/6 | 0/6 | 0/6 |
| Acute kidney injuryRenal and urinary disorders | 0/6 | 1/7 | 0/6 | 0/6 | 0/6 | 0/7 | 0/6 | 0/6 | 0/6 |
| Event | End Stage Renal Disease: Microdose Cocktail Alone | Severe Impairment: Microdose Cocktail Alone | Severe Impairment: Microdose Cocktail + Rifampin | Moderate Impairment: Microdose Cocktail Alone | Moderate Impairment: Microdose Cocktail + Rifampin | Mild Impairment: Microdose Cocktail Alone | Mild Impairment: Microdose Cocktail + Rifampin | Healthy Control: Microdose Cocktail Alone | Healthy Control: Microdose Cocktail + Rifampin |
|---|---|---|---|---|---|---|---|---|---|
| SomnolenceNervous system disorders | 0/6 | 2/7 | 0/6 | 2/6 | 0/6 | 2/7 | 0/6 | 0/6 | 0/6 |
| DiarrhoeaGastrointestinal disorders | 0/6 | 0/7 | 1/6 | 0/6 | 0/6 | 0/7 | 0/6 | 0/6 | 0/6 |
| FatigueGeneral disorders | 0/6 | 0/7 | 0/6 | 0/6 | 0/6 | 0/7 | 1/6 | 0/6 | 0/6 |
| HeadacheNervous system disorders | 1/6 | 0/7 | 0/6 | 0/6 | 1/6 | 0/7 | 1/6 | 0/6 | 0/6 |
| Blood potassium decreasedInvestigations | 0/6 | 0/7 | 0/6 | 0/6 | 0/6 | 1/7 | 0/6 | 0/6 | 0/6 |
| Age, Continuous(Years) | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control | Total |
|---|---|---|---|---|---|---|
| Mean | 56.7 ± 8.04 | 64.9 ± 7.10 | 67.0 ± 11.19 | 65.4 ± 8.90 | 57.8 ± 7.88 | 62.5 ± 9.15 |
| Sex: Female, Male(Participants) | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control | Total |
|---|---|---|---|---|---|---|
| Female | 0 | 1 | 4 | 3 | 3 | 11 |
| Male | 6 | 6 | 2 | 4 | 3 | 21 |
| Ethnicity (NIH/OMB)(Participants) | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 5 | 4 | 5 | 6 | 20 |
| Not Hispanic or Latino | 6 | 2 | 2 | 2 | 0 | 12 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | End-Stage Renal Disease | Severe Impairment | Moderate Impairment | Mild Impairment | Healthy Control | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | 0 | 1 |
| Asian | 0 | 0 | 00 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 6 | 0 | 0 | 3 | 0 | 9 |
| White | 0 | 7 | 6 | 3 | 6 | 22 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Data sharing details ↗ · engagezone.msd.com
Ran from Mar 2018 to primary completion in Aug 2018, 5 months.
Results were first posted in Jan 2020, 1 year 5 months after primary completion.
Of 212 industry-sponsored phase 1 interventional studies under Renal Insufficiency, half reached primary completion within 8 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 15. This study's 5 months is below that.
Counting every sponsor, half of 230 studies reached it within 8 months; a quarter within 5 and three quarters within 16.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Midazolam · Dabigatran · Pitavastatin