Phase 1
Completed N=36
Effect of Renal Impairment on the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Ertugliflozin in Participants With Type 2 Diabetes Mellitus (MK-8835-009)
Source: ClinicalTrials.gov NCT01948986 ↗Enrolled (actual)
36
Serious AEs
0.0%
Results posted
Feb 2019
Primary outcomePrimary: Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) — 1199; 1908; 2075; 1895 ng•hr/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 Extrapolated to Infinite Time (AUCinf) |
1199; 1908; 2075; 1895; 1236 | — |
| PRIMARY Area Under the Plasma Concentration-Time Profile for Ertugliflozin From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) |
1174; 1814; 2011; 1816; 1214 | — |
| PRIMARY Apparent Clearance (CL/F) for Plasma Ertugliflozin |
208.8; 130.9; 120.4; 132.0; 202.1 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) for Ertugliflozin |
215.9; 313.1; 305.7; 196.4; 219.3 | — |
| PRIMARY Time for Cmax (Tmax) for Plasma Ertugliflozin |
1.00; 1.50; 1.50; 1.51; 1.00 | — |
| PRIMARY Terminal Half-Life (t1/2) for Plasma Ertugliflozin |
14.62; 25.94; 22.89; 24.17; 17.71 | — |
| PRIMARY Apparent Volume of Distribution Following Oral Administration (Vz/F) for Plasma Ertugliflozin |
239.7; 254.5; 228.3; 268.8; 304.5 | — |
| PRIMARY Unbound Fraction (Fu) for Plasma Ertugliflozin |
0.03437; 0.03458; 0.03804; 0.04107; 0.03484 | — |
| PRIMARY Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) |
0.1494; 0.1081; 0.09682; 0.05843; 0.1231 | — |
| PRIMARY Percent of Dose Recovered Unchanged in Urine From 0 to 96 Hours Postdose (for Ertugliflozin Only) (Ae96%) |
0.9952; 0.7200; 0.6456; 0.3893; 0.8213 | — |
| PRIMARY Renal Clearance (CLr) for Urinary Ertugliflozin |
2.092; 0.9872; 0.8024; 0.5360; 1.682 | — |
| PRIMARY Number of Participants Who Experienced an Adverse Event (AE) |
1; 2; 2; 3; 4 | — |
| PRIMARY Number of Participants Who Discontinued Study Due to an AE |
0; 0; 0; 0; 0 | — |
| PRIMARY Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 Extrapolated to Infinite Time (AUCinf) |
1559; 2620; 3668; 2742; 1113 | — |
| PRIMARY Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06481944 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) |
1536; 2517; 3552; 2642; 1090 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06481944 |
217.8; 309.0; 358.5; 218.6; 168.6 | — |
| PRIMARY Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06481944 |
2.00; 2.00; 3.00; 3.00; 2.00 | — |
| PRIMARY Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06481944 |
16.68; 22.04; 23.33; 22.83; 17.51 | — |
| PRIMARY Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06481944 |
7.056; 5.861; 3.768; 1.630; 6.225 | — |
| PRIMARY CLr for Urinary Glucuronide Metabolite PF-06481944 |
76.28; 38.73; 17.67; 10.27; 94.53 | — |
| PRIMARY Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 Extrapolated to Infinite Time (AUCinf) |
383.9; 604.1; 950.9; 975.0; 337.6 | — |
| PRIMARY Area Under the Plasma Concentration-Time Profile for Glucuronide Metabolite PF-06685948 From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) |
371.9; 579.8; 917.7; 922.1; 329.1 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) for Glucuronide Metabolite PF-06685948 |
44.44; 53.56; 63.10; 46.42; 43.90 | — |
| PRIMARY Time for Cmax (Tmax) for Plasma Glucuronide Metabolite PF-06685948 |
2.00; 3.00; 4.00; 3.51; 2.00 | — |
| PRIMARY Terminal Half-life (t1/2) for Plasma Glucuronide Metabolite PF-06685948 |
14.87; 21.71; 22.49; 25.22; 15.68 | — |
| PRIMARY Cumulative Amount of Drug Recovered Unchanged in Urine to 96 Hours Post Dose (Ae96) for Glucuronide Metabolite PF-06685948 |
0.9575; 0.7882; 0.6603; 0.3195; 0.8287 | — |
| PRIMARY Renal Clearance (CLr) for Urinary Glucuronide Metabolite PF-06685948 |
41.82; 22.50; 11.95; 5.778; 41.42 | — |
| PRIMARY Change From Baseline in 24 Hour Inhibition of Glucose Reabsorption |
33.34; 25.58; 28.84; 24.25; 29.19 | — |
| PRIMARY Change From Baseline in 24 Hour Fluid Balance |
-660.67; -937.00; -696.38; 111.50; -478.63 | — |
| SECONDARY Urinary Glucose Excretion Over 24 Hours (UGE0-24hr) for Ertugliflozin |
72.31; 35.98; 27.55; 10.09; 46.33 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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)
- 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.
Data sourced from ClinicalTrials.gov (NCT01948986). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.