Renal InsufficiencyPhase 1NCT03311841

Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin in Participants With Renal Insufficiency in the Presence and Absence of Rifampin (MK-0000-386)

A Phase 1 study testing Midazolam oral solution, Dabigatran and pitavastatin oral solution and Atorvastatin and rosuvastatin oral solution in people with Renal Insufficiency, run by Merck Sharp & Dohme LLC at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this open-label, 2-period, fixed-sequence study is to characterize the plasma pharmacokinetic profiles of midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin following a single oral dose administration of a microdose cocktail in healthy participants, in participants with mild, moderate… Read more about this study

Who is it for?: Ages 18 to 78 yearsHealthy volunteers can take part
Conditions the study is for: Renal Insufficiency
What is being tested?: Midazolam oral solution, Dabigatran and pitavastatin oral solution and Atorvastatin and rosuvastatin oral solution
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 2 sitesUnited States
Study dates: 1 Mar 2018to 2 Aug 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 78 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
a female must be non-pregnant, non-breast feeding and if she is of reproductive potential: must agree to use (and/or have their partner use) two acceptable methods of birth control beginning at screening, throughout the study and until 2 weeks after the last dosing of study drug
a female of non-childbearing potential: must have undergone a sterilization procedure at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at least 1 year prior to the first dose
a non-vasectomized male participant must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after the last dose of study drug
a male participant must agree not to donate sperm from dosing until 90 days after the last dose of study drug
has a body mass index (BMI) ≤ 40.0 kg/m^2

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is a non-smoker or moderate smoker (≤ 20 cigarettes/day or the equivalent)
Participants with mild, moderate or severe renal impairment or end stage renal disease:
has a clinical diagnosis of renal impairment and meets the protocol-specified renal impairment function qualifications at the prestudy visit (screening)
Healthy participants:
has baseline creatinine clearance ≥ 90 mL/min based on Cockcroft-Gault equation
is judged to be in good health based on medical history, physical examination, vital signs, pulse oximetry, and laboratory safety tests

Who cannot join

All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
history or presence of clinically significant medical or psychiatric condition or disease
history of stroke, chronic seizures, or major neurological disorders
history of malignant neoplastic disease
history or presence of alcoholism or drug abuse within the past 6 months

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female participant who is pregnant or lactating
Participants with mild, moderate or severe renal impairment:
has had a renal transplant or has had nephrectomy
has uncontrolled type 2 diabetes mellitus (T2DM), a history of Type 1 diabetes, or ketoacidosis
history of significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
Participants with end stage renal disease (ESRD):
had a failed renal allograft within the last 2 years prior to the first dose, or a successful renal allograft
has uncontrolled T2DM, a history of Type 1 diabetes, or ketoacidosis
history of significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, respiratory, or genitourinary diseases
Healthy participants:
history of hypoglycemia, glucose intolerance, T2DM, or ketoacidosis
history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Clinical Pharmacology of Miami ( Site 0001)
Hialeah, Florida, 33014
Orlando Clinical Research Center ( Site 0002)
Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A Study to Assess the Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin Administered as Microdoses in Subjects With Varying Degrees of Renal Insufficiency in the Presence and Absence of Rifampin

Conditions: Renal Insufficiency
Being tested: Midazolam oral solution, Dabigatran and pitavastatin oral solution, Atorvastatin and rosuvastatin oral solution, Rifampin
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Midazolam oral solutionDrug
Midazolam hydrochloride 10 μg (1 mL of 10 μg/mL oral solution), administered orally as part of a microdose cocktail
Dabigatran and pitavastatin oral solutionDrug
375/10 μg dabigatran etexilate and pitavastatin (1 mL of 375/10 μg/mL oral solution), administered orally as part of a microdose cocktail
Atorvastatin and rosuvastatin oral solutionDrug
100/50 μg atorvastatin and rosuvastatin (2 mL of 50/25 μg/mL oral solution), administered orally as part of a microdose cocktail
RifampinDrug
Rifampin 600 mg single dose (two 300 mg capsules) administered orally

Study groups in NCT03311841
Study group	Role	What they receive
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. Receives: Drug: Midazolam oral solution; Drug: Dabigatran and pitavastatin oral solution; Drug: Atorvastatin and rosuvastatin oral solution
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. Receives: Drug: Midazolam oral solution; Drug: Dabigatran and pitavastatin oral solution; Drug: Atorvastatin and rosuvastatin oral solution; Drug: Rifampin
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. Receives: Drug: Midazolam oral solution; Drug: Dabigatran and pitavastatin oral solution; Drug: Atorvastatin and rosuvastatin oral solution; Drug: Rifampin
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. Receives: Drug: Midazolam oral solution; Drug: Dabigatran and pitavastatin oral solution; Drug: Atorvastatin and rosuvastatin oral solution; Drug: Rifampin
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. Receives: Drug: Midazolam oral solution; Drug: Dabigatran and pitavastatin oral solution; Drug: Atorvastatin and rosuvastatin oral solution; Drug: Rifampin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

Secondary outcomes (8)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 20182 Aug 2018

First posted17 Oct 2017
Study start1 Mar 2018
Primary completion2 Aug 2018
Study completion2 Aug 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Renal InsufficiencyStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03311841
Sponsor's protocol ID: 0000-386
Other IDs: MK-0000-386, CA21005
Status last verified: Dec 2019
First submitted: 12 Oct 2017
Last updated: 9 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Assess the Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin Administered as Microdoses in Subjects With Varying Degrees of Renal Insufficiency in the Presence and Absence of Rifampin
ClinicalTrials.gov ID: NCT03311841
Acronym / sponsor ID: 0000-386
Conditions: Renal Insufficiency
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 1 Mar 2018 (actual)
Primary completion: 2 Aug 2018 (actual)
Study completion: 2 Aug 2018 (actual)
First posted: 17 Oct 2017 (actual)
Results: Posted 9 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
End Stage Renal Disease	Experimental	Drug: Midazolam oral solution, Drug: Dabigatran and pitavastatin oral solution, Drug: Atorvastatin and rosuvastatin oral solutionParticipants requiring hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). A washout period of at least 14 days will separate dosings.
Severe Impairment	Experimental	Drug: Midazolam oral solution, Drug: Dabigatran and pitavastatin oral solution, Drug: Atorvastatin and rosuvastatin oral solution, Drug: RifampinParticipants with <30 mL/min/1.73m^2 estimated glomerular filtration rate (eGFR) not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Moderate Impairment	Experimental	Drug: Midazolam oral solution, Drug: Dabigatran and pitavastatin oral solution, Drug: Atorvastatin and rosuvastatin oral solution, Drug: RifampinParticipants with 30 to <60 mL/min/1.73m^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Mild Impairment	Experimental	Drug: Midazolam oral solution, Drug: Dabigatran and pitavastatin oral solution, Drug: Atorvastatin and rosuvastatin oral solution, Drug: RifampinParticipants with 60 to <90 mL/min/1.73m^2 eGFR not on hemodialysis. Period 1/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution). Period 2/Day 1: participants receive a single oral dose of the microdose cocktail (midazolam oral solution, dabigatran etexilate and pitavastatin oral solution, atorvastatin and rosuvastatin oral solution) and rifampin. A washout period of at least 14 days will separate dosings.
Healthy Control	Active comparator	Drug: Midazolam oral solution, Drug: Dabigatran and pitavastatin oral solution, Drug: Atorvastatin and rosuvastatin oral solution, Drug: RifampinParticipants 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.

Who may qualify

Ages: 18 to 78 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
a female must be non-pregnant, non-breast feeding and if she is of reproductive potential: must agree to use (and/or have their partner use) two acceptable methods of birth control beginning at screening, throughout the study and until 2 weeks after the last dosing of study drug
a female of non-childbearing potential: must have undergone a sterilization procedure at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at least 1 year prior to the first dose
a non-vasectomized male participant must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after the last dose of study drug
a male participant must agree not to donate sperm from dosing until 90 days after the last dose of study drug

Key exclusion criteria (18 listed)

All participants (with mild, moderate or severe renal impairment, end stage renal disease, or healthy):
is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
history or presence of clinically significant medical or psychiatric condition or disease
history of stroke, chronic seizures, or major neurological disorders
history of malignant neoplastic disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Midazolam oral solutionMidazolam hydrochloride 10 μg (1 mL of 10 μg/mL oral solution), administered orally as part of a microdose cocktail	Drug	End Stage Renal Disease, Healthy Control, Mild Impairment, Moderate Impairment, Severe Impairment
Dabigatran and pitavastatin oral solution375/10 μg dabigatran etexilate and pitavastatin (1 mL of 375/10 μg/mL oral solution), administered orally as part of a microdose cocktail	Drug	End Stage Renal Disease, Healthy Control, Mild Impairment, Moderate Impairment, Severe Impairment
Atorvastatin and rosuvastatin oral solution100/50 μg atorvastatin and rosuvastatin (2 mL of 50/25 μg/mL oral solution), administered orally as part of a microdose cocktail	Drug	End Stage Renal Disease, Healthy Control, Mild Impairment, Moderate Impairment, Severe Impairment
RifampinRifampin 600 mg single dose (two 300 mg capsules) administered orally	Drug	Healthy Control, Mild Impairment, Moderate Impairment, Severe Impairment

Primary outcome

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1
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
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.
Effect of Rifampin on AUC0-inf Post-dose 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
To evaluate the effect of a single oral dose of rifampin on the AUC0-inf of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include data from the end-stage renal disease participants as they did not receive rifampin during Period 2.
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1
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
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.
Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1
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
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.
Maximum Plasma Concentration (Cmax) Post-dose Period 1
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose
Cmax is the peak plasma concentration of study drug after administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Plasma Concentration at 24 Hours (C24) Post-dose Period 1
Time frame: 24 hours post-dose
C24hr is a measure of the plasma study drug concentration 24 hours post-dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Time to Maximum Plasma Concentration (Tmax) Post-dose Period 1
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose
Tmax is the amount of time to reach maximum (peak) plasma drug concentration following drug administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Apparent Plasma Terminal Half-life (t1/2) Post-dose Period 1
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose
T1/2 is the elimination half-life of study drug. T1/2 is the time it takes for half of the study drug in the blood plasma to dissipate. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis.
Apparent Clearance After Extravascular Administration (CL/F) Post-dose Period 1
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose
CL/F is the rate at which study drug was removed from the body. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. CL/F was to be calculated for the parent plasma analytes only, midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin.
Apparent Volume of Distribution During the Terminal Phase (Vz/F) Post-dose Period 1
Time frame: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose
Vz/F is the distribution of study drug between the plasma and the rest of the body after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. Vz/F was to be calculated for the parent plasma analytes only, midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin.

8 secondary outcomes

Effect of Rifampin on AUC0-24 Post-dose 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
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
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
Time frame: 24 hours post-dose
Effect of Rifampin on Tmax Post-dose 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
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
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
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

Results and safety

Results posted to the registry on 9 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
End-Stage Renal Disease	6	6
Severe Impairment	7	7
Moderate Impairment	6	6
Mild Impairment	7	7
Healthy Control	6	6

Primary outcome: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1

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. Geometric least squares mean (95% Confidence Interval). Unit: pg*hr/mL

Measure	End-Stage Renal Disease n = 6	Severe Impairment n = 7	Moderate Impairment n = 6	Mild Impairment n = 6	Healthy Control n = 6
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)

Mild Impairment vs Healthy Control: Geometric least squares mean ratio: 0.64 (95% CI 0.37 to 1.11)
Moderate Impairment vs Healthy Control: Geometric least squares mean ratio: 1.33 (95% CI 0.77 to 2.31)
Severe Impairment vs Healthy Control: Geometric least squares mean ratio: 0.95 (95% CI 0.56 to 1.62)

Population analysed: 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.

Primary outcome: Effect of Rifampin on AUC0-inf Post-dose 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. Geometric least squares mean (95% Confidence Interval). Unit: pg*hr/mL

Measure	End Stage Renal Disease (Period 2) n = 0	Severe Impairment (Period 2) n = 6	Moderate Impairment (Period 2) n = 6	Mild Impairment (Period 2) n = 6	Healthy Control (Period 2) n = 6
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)

Population analysed: 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.

Primary outcome: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1

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. Geometric mean (95% Confidence Interval). Unit: pg*hr/mL

Measure	End-Stage Renal Disease n = 6	Severe Impairment n = 7	Moderate Impairment n = 6	Mild Impairment n = 6	Healthy Control n = 6
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)

Mild Impairment vs Healthy Control: Geometric least squares mean ratio: 0.67 (95% CI 0.40 to 1.11)
Moderate Impairment vs Healthy Control: Geometric least squares mean ratio: 1.26 (95% CI 0.76 to 2.09)
Severe Impairment vs Healthy Control: Geometric least squares mean ratio: 0.93 (95% CI 0.57 to 1.52)

Population analysed: 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.

Primary outcome: Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1

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. Geometric mean (95% Confidence Interval). Unit: pg*hr/mL

Measure	End-Stage Renal Disease n = 6	Severe Impairment n = 7	Moderate Impairment n = 6	Mild Impairment n = 6	Healthy Control n = 6
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)

Mild Impairment vs Healthy Control: Geometric least squares mean ratio: 0.63 (95% CI 0.36 to 1.11)
Moderate Impairment vs Healthy Control: Geometric least squares mean ratio: 1.30 (95% CI 0.75 to 2.28)
Severe Impairment vs Healthy Control: Geometric least squares mean ratio: 0.94 (95% CI 0.55 to 1.61)

Population analysed: 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.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up tp approximately 30 days (including 14 days following the last dose). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
End Stage Renal Disease: Microdose Cocktail Alone	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Severe Impairment: Microdose Cocktail Alone	1 of 7 (14.3%)	2 of 7 (28.6%)	0 of 7
Severe Impairment: Microdose Cocktail + Rifampin	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Moderate Impairment: Microdose Cocktail Alone	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Moderate Impairment: Microdose Cocktail + Rifampin	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Mild Impairment: Microdose Cocktail Alone	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7
Mild Impairment: Microdose Cocktail + Rifampin	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Healthy Control: Microdose Cocktail Alone	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Healthy Control: Microdose Cocktail + Rifampin	0 of 6 (0%)	0 of 6 (0%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1 (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). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03311841.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2020; AzTrials last refreshed its copy on 8 Nov 2026.