Renal ImpairmentPhase 1NCT01948986

Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Ertugliflozin in Participants With Type 2 Diabetes Mellitus (MK-8835-009)

A Phase 1 study testing Ertugliflozin in people with Renal Impairment and Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

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

This is a study to evaluate the effect of renal impairment on the pharmacokinetics, pharmacodynamics, safety and tolerability of ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and in healthy participants with normal renal function. Read more about this study

Who is it for?: Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Renal Impairment, Type 2 Diabetes Mellitus
What is being tested?: Ertugliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: No sites listed yet
Study dates: 1 Oct 2013to 16 Oct 2014
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 80 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Body Mass Index (BMI) of approximately 18 to 40 kg/m^2
Stable renal function
Male or female not of reproductive potential
Female of reproductive potential must agree or have their partner agree to use 2 acceptable methods of contraception
Healthy subjects determined to be healthy by investigator screening
T2DM participants have a diagnosis of T2DM as per American Diabetes Association guidelines
T2DM participants to be on a stable anti-hyperglycemic regimen with no new drug or drug dosage within 8 weeks of study participation. Variations in daily dose of insulin up to 10% are permitted.

Who cannot join

A positive urine drug screen for drugs of abuse or recreational drugs
Pregnant or nursing females
History of abuse of alcohol or illicit drugs
Significant renal or urinary disease within 6 months of study participation
History of malignancy within the past 5 years basal cell carcinoma of the skin or cervical cancer in situ
History of human immunodeficiency virus (HIV)

Show all 30Show fewer

History of blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
Any acute disease state (eg, , vomiting, fever, diarrhea) within 7 days before study participation
Treatment with an investigational drug within 30 days of study participation
Use of herbal supplements within 28 days prior to study participation
Any clinically significant malabsorption condition
Blood donation (excluding plasma donations) of approximately 1 pint within 56 days prior to study participation
History of sensitivity to ertugliflozin or other Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors
History of sensitivity to heparin or heparin-induced thrombocytopenia
Unwilling or unable to comply with the study Lifestyle Guidelines
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease including clinically relevant and significant drug allergies
Use of prescription drugs (hormonal methods of birth control are allowed), vitamins and dietary supplements within 7 days of study participation
For T2DM participants, history of type 1 diabetes mellitus or a history of ketoacidosis
For T2DM participants, clinically significant electrocardiogram abnormality
For T2DM participants, history of myocardial infarction, unstable angina, coronary revascularization, stroke or transient ischemic attack within 3 months of study participation
For T2DM participants, heart failure defined as New York Heart Association Functional Class III-IV
For T2DM participants, renal allograft recipients
For T2DM participants, requiring dialysis
For T2DM participants, strict fluid restriction
For T2DM participants, urinary incontinence
For T2DM participants, acute renal disease
For T2DM participants, significant hepatic, cardiac, or pulmonary disease or clinically nephrotic
For T2DM participants, prescription and over-the-counter medication that is not taken according to a stable regimen for 7 days before study participation
For T2DM participants, on metformin should not be enrolled if their baseline renal function is outside the approved product labeling
For T2DM participants receiving any of the following medications within 7 days of study participation: 1. Other SGLT2 inhibitors (eg, dapagliflozin, canagliflozin, empagliflozin); 2. Other injectable anti-hyperglycemic agents including pramlintide or Glucagon-like peptide-1 (GLP-1) analogues; 3. Any immunosuppressive drugs, including cyclosporine, tacrolimus, sirolimus; 4. Oral corticosteroids (note that inhaled, nasal and topical corticosteroids are permitted); 5. Any potent drug-metabolizing enzyme-inducing drug, including rifampin, phenytoin, and carbamazepine; 6. Probenecid, valproic acid, gemfibrozil.

About this study

Official title: A Phase 1, Non-Randomized, Open-Label, Single Dose Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus

Conditions: Renal Impairment, Type 2 Diabetes Mellitus
Being tested: Ertugliflozin
Medical subject headings: Renal Insufficiency, Diabetes Mellitus, Type 2

What participants receive

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

ErtugliflozinDrug
Also called MK-8835
Single oral administration of 3 X 5 mg tablets.

Study groups in NCT01948986
Study group	Role	What they receive
Ertugliflozin 15 mg (T2DM with Normal Renal Function)	Experimental	Ertugliflozin (15 mg), oral, administered in participants with T2DM and with normal renal function Receives: Drug: Ertugliflozin
Ertugliflozin 15 mg (T2DM with Mild Renal Impairment)	Experimental	Ertugliflozin (15 mg), oral, administered in participants with T2DM and with mild renal impairment Receives: Drug: Ertugliflozin
Ertugliflozin 15 mg (T2DM with Moderate Renal Impairment)	Experimental	Ertugliflozin (15 mg), oral, administered in participants with T2DM and with moderate renal impairment Receives: Drug: Ertugliflozin
Ertugliflozin 15 mg (T2DM with Severe Renal Impairment)	Experimental	Ertugliflozin (15 mg), oral, administered in participants with T2DM and with severe renal impairment Receives: Drug: Ertugliflozin
Ertugliflozin, 15 mg (Healthy Part. with Normal Renal Funct.)	Experimental	Ertugliflozin (15 mg), oral, administered in participants with healthy participants and with normal renal function Receives: Drug: Ertugliflozin

What is being measured

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

Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf)
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Apparent Clearance (CL/F) for Plasma Ertugliflozin
CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Time for Cmax (Tmax) for Plasma Ertugliflozin
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Terminal Half-Life (t1/2) for Plasma Ertugliflozin
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin
VzF is the apparent volume of distribution during terminal phase after oral / extravascular administration. VzF = Dose/(AUCinf × kel) where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Unbound Fraction (Fu) for Plasma Ertugliflozin
Fraction of unbound (not protein-bound) drug in plasma. Fu is determined using in vitro equilibrium dialysis method: concentration in buffer at equilibrium/concentration in plasma at equilibrium. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96)
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%)
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Ae96% = Ae96 / Dose × 100 Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Renal Clearance (CLr) for Urinary Ertugliflozin
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Number of Participants Who Experienced an Adverse Event (AE)
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measured: Up to 19 days
Number of Participants Who Discontinued Study Due to an AE
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Measured: Up to 5 days
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf)
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
CLr for Urinary Glucuronide Metabolite PF-06481944
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf)
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined.
Measured: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Measured: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption
Inhibition of Glucose Reabsorption = 100 * urinary glucose excretion / (eGFR(ML/MIN) * Weighted Mean Plasma Glucose * 0.0144). 0.0144 is a unit conversion factor used to make the ratio unitless. Geometric Coefficient of Variation was reported as a percent.
Measured: Baseline and 24 Hours
Change From Baseline in 24 Hour Fluid Balance
Fluid balance = fluid intake - urine output.
Measured: For 24 hours before Baseline (-48 to -24 hours) and up to 24 hours after dosing on Day 1 (Up to 24 hours)

Secondary outcomes (1)

Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin
Participants were asked to void at the end of each prescribed interval with forced voids prior to start and at the end of each interval.
Measured: 0-4, 4-8, 8-12, 12-24 hours after dosing on Day 1

Timeline

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

1 Oct 201316 Oct 2014

First posted24 Sep 2013 (estimated)
Study start1 Oct 2013
Primary completion6 Oct 2014
Study completion16 Oct 2014

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.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Renal ImpairmentStudies 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: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01948986
Sponsor's protocol ID: 8835-009
Other IDs: B1521023, MK-8835-009
Status last verified: Oct 2018
First submitted: 20 Sep 2013
Last updated: 18 Feb 2019
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

Publications

Sahasrabudhe V, Terra SG, Hickman A, Saur D, Shi H, O'Gorman M, Zhou Z, Cutler DL. The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2017 Nov;57(11):1432-1443. doi: 10.1002/jcph.955. Epub 2017 Jul 13.
PubMed 28703316
Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
PubMed 34213819
Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.
PubMed 33813736

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?

Official record

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All Renal Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Non-Randomized, Open-Label, Single Dose Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT01948986
Acronym / sponsor ID: 8835-009
Conditions: Renal Impairment, Type 2 Diabetes Mellitus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Collaborators: Pfizer
Study start: 1 Oct 2013 (actual)
Primary completion: 6 Oct 2014 (actual)
Study completion: 16 Oct 2014 (actual)
First posted: 24 Sep 2013 (estimated)
Results: Posted 18 Feb 2019

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
Ertugliflozin 15 mg (T2DM with Normal Renal Function)	Experimental	Drug: ErtugliflozinErtugliflozin (15 mg), oral, administered in participants with T2DM and with normal renal function
Ertugliflozin 15 mg (T2DM with Mild Renal Impairment)	Experimental	Drug: ErtugliflozinErtugliflozin (15 mg), oral, administered in participants with T2DM and with mild renal impairment
Ertugliflozin 15 mg (T2DM with Moderate Renal Impairment)	Experimental	Drug: ErtugliflozinErtugliflozin (15 mg), oral, administered in participants with T2DM and with moderate renal impairment
Ertugliflozin 15 mg (T2DM with Severe Renal Impairment)	Experimental	Drug: ErtugliflozinErtugliflozin (15 mg), oral, administered in participants with T2DM and with severe renal impairment
Ertugliflozin, 15 mg (Healthy Part. with Normal Renal Funct.)	Experimental	Drug: ErtugliflozinErtugliflozin (15 mg), oral, administered in participants with healthy participants and with normal renal function

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Body Mass Index (BMI) of approximately 18 to 40 kg/m^2
Stable renal function
Male or female not of reproductive potential
Female of reproductive potential must agree or have their partner agree to use 2 acceptable methods of contraception
Healthy subjects determined to be healthy by investigator screening

Key exclusion criteria (30 listed)

A positive urine drug screen for drugs of abuse or recreational drugs
Pregnant or nursing females
History of abuse of alcohol or illicit drugs
Significant renal or urinary disease within 6 months of study participation
History of malignancy within the past 5 years basal cell carcinoma of the skin or cervical cancer in situ

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
ErtugliflozinAlso: MK-8835Single oral administration of 3 X 5 mg tablets.	Drug	Ertugliflozin 15 mg (T2DM with Mild Renal Impairment), Ertugliflozin 15 mg (T2DM with Moderate Renal Impairment), Ertugliflozin 15 mg (T2DM with Normal Renal Function), Ertugliflozin 15 mg (T2DM with Severe Renal Impairment), Ertugliflozin, 15 mg (Healthy Part. with Normal Renal Funct.)

Primary outcome

Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf)
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Apparent Clearance (CL/F) for Plasma Ertugliflozin
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
CL/F is a calculation of the rate at which a drug is removed from the body via renal, hepatic and other clearance pathways, expressed as volume (milliliters) per unit of time (minutes). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Time for Cmax (Tmax) for Plasma Ertugliflozin
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Terminal Half-Life (t1/2) for Plasma Ertugliflozin
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
VzF is the apparent volume of distribution during terminal phase after oral / extravascular administration. VzF = Dose/(AUCinf × kel) where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Geometric Coefficient of Variation was reported as a percent.
Unbound Fraction (Fu) for Plasma Ertugliflozin
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Fraction of unbound (not protein-bound) drug in plasma. Fu is determined using in vitro equilibrium dialysis method: concentration in buffer at equilibrium/concentration in plasma at equilibrium. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined.
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96)
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%)
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96% = Ae96 / Dose × 100 Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
Renal Clearance (CLr) for Urinary Ertugliflozin
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent.
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 19 days
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Number of Participants Who Discontinued Study Due to an AE
Time frame: Up to 5 days
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf)
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined. Geometric Coefficient of Variation was reported as a percent.
Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined.
Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF 06481944 was determined.
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Geometric Coefficient of Variation was reported as a percent.
CLr for Urinary Glucuronide Metabolite PF-06481944
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Geometric Coefficient of Variation was reported as a percent.
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf)
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area under the plasma concentration-time profile from Time 0 extrapolated to infinite time. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Area under the plasma concentration-time profile from Time 0 to the time of the last quantifiable concentration (Clast). Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose and is observed directly from data as time of first occurrence. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined.
Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948
Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose
T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. T1/2 = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined.
Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. Ae96 = Sum of [urine concentration × sample volume] for each collection interval from 0 to 96 hours post dose. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948
Time frame: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours after dosing on Day 1
Urine samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of ertugliflozin was determined. CLr is Renal Clearance (Ae96 / AUC96), where Ae96 is the cumulative amount of drug recovered unchanged in urine to 96 hours post dose and AUC96 was the area under the concentration-time profile form time 0 to 96 hours. Blood samples were taken at pre-dose up to 96 hours post-dose, from which the concentration of glucuronide metabolite PF-06685948 was determined. Geometric Coefficient of Variation was reported as a percent.
Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption
Time frame: Baseline and 24 Hours
Inhibition of Glucose Reabsorption = 100 * urinary glucose excretion / (eGFR(ML/MIN) * Weighted Mean Plasma Glucose * 0.0144). 0.0144 is a unit conversion factor used to make the ratio unitless. Geometric Coefficient of Variation was reported as a percent.
Change From Baseline in 24 Hour Fluid Balance
Time frame: For 24 hours before Baseline (-48 to -24 hours) and up to 24 hours after dosing on Day 1 (Up to 24 hours)
Fluid balance = fluid intake - urine output.

1 secondary outcome

Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin
Time frame: 0-4, 4-8, 8-12, 12-24 hours after dosing on Day 1

Results and safety

Results posted to the registry on 18 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ertugliflozin 15 mg (T2DM With Normal Renal Function)	6	6
Ertugliflozin 15 mg (T2DM With Mild Renal Impairment)	8	8
Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment)	8	8
Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment)	6	6
Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function)	8	8

Primary outcome: Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf)

Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng•hr/mL

Measure	Ertugliflozin 15 mg (T2DM With Normal Renal Function) n = 6	Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) n = 6	Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) n = 8
Value	1199 (42)	1908 (28)	2075 (19)	1895 (23)	1236 (27)

Ertugliflozin 15 mg (T2DM With Normal Renal Function) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Heathy Normal/T2DM Normal): 103.07 (90% CI 80.32 to 132.27)
Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Mild Renal Impair./Pooled Norm.): 156.34 (90% CI 127.83 to 191.23)
Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Mod. Renal Impair./Pooled Norm.): 170.04 (90% CI 139.02 to 207.98)

Population analysed: The analysis population was defined as all treated participants who had at least one concentration measurement for AUCinf.

Primary outcome: Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)

Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng•hr/mL

Measure	Ertugliflozin 15 mg (T2DM With Normal Renal Function) n = 6	Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) n = 6	Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) n = 8
Value	1174 (42)	1814 (27)	2011 (18)	1816 (23)	1214 (27)

Ertugliflozin 15 mg (T2DM With Normal Renal Function) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Heathy Normal/T2DM Normal): 103.42 (90% CI 80.66 to 132.61)
Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Mild Renal Impair./Pooled Norm.): 151.63 (90% CI 124.05 to 185.34)
Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Mod. Renal Impair./Pooled Norm.): 168.11 (90% CI 137.53 to 205.49)

Population analysed: The analysis population was defined as all treated participants who had at least one concentration measurement for AUClast.

Primary outcome: Apparent Clearance (CL/F) for Plasma Ertugliflozin

Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: mL/min

Measure	Ertugliflozin 15 mg (T2DM With Normal Renal Function) n = 6	Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) n = 6	Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) n = 8
Value	208.8 (42)	130.9 (28)	120.4 (19)	132.0 (23)	202.1 (27)

Population analysed: The analysis population was defined as all treated participants who had at least one concentration measurement for CL/F.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin

Time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Ertugliflozin 15 mg (T2DM With Normal Renal Function) n = 6	Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) n = 8	Ertugliflozin 15 mg (T2DM and With Severe Renal Impairment) n = 6	Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function) n = 8
Value	215.9 (35)	313.1 (30)	305.7 (23)	196.4 (28)	219.3 (26)

Ertugliflozin 15 mg (T2DM With Normal Renal Function) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Heathy Normal/T2DM Normal): 101.57 (90% CI 78.83 to 130.87)
Ertugliflozin 15 mg (T2DM With Mild Renal Impairment) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Mild Renal Impair./Pooled Norm.): 143.74 (90% CI 117.15 to 176.37)
Ertugliflozin 15 mg (T2DM With Moderate Renal Impairment) vs Ertugliflozin 15 mg (Healthy Part. With Normal Renal Function): Ratio (Mod. Renal Impair./Pooled Norm.): 140.37 (90% CI 114.40 to 172.23)

Population analysed: The analysis population was defined as all treated participants who had at least one concentration measurement for Cmax.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 19 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
T2DM Normal Renal Function	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
T2DM Mild Renal Impairment	0 of 8 (0%)	2 of 8 (25%)	Not reported
T2DM Moderate Renal Impairment	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
T2DM Severe Renal Impairment	0 of 6 (0%)	3 of 6 (50%)	Not reported
Healthy Normal Renal Function	0 of 8 (0%)	4 of 8 (50%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28703316Sahasrabudhe V, Terra SG, Hickman A, Saur D, Shi H, O'Gorman M, Zhou Z, Cutler DL. The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus. J Clin Pharmacol. 2017 Nov;57(11):1432-1443. doi: 10.1002/jcph.955. Epub 2017 Jul 13.
Derived from this study: PubMed 34213819Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.
Derived from this study: PubMed 33813736Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.
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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ertugliflozin in people with Renal Impairment and Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

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 7 inclusion and 30 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 18 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

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 18 Feb 2019). 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 Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) (time frame: Time 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours post-dose). The study lists 29 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 NCT01948986, which also lists 3 linked publications.

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 18 Feb 2019.