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

NCT ID: NCT01948986

Last Updated: 2019-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-01
• Study Completion Date: 2014-10-16

Brief 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.

Conditions

Renal Impairment; Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ertugliflozin 15 mg (T2DM with Normal Renal Function)

Ertugliflozin (15 mg), oral, administered in participants with T2DM and with normal renal function

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

Single oral administration of 3 X 5 mg tablets.

Ertugliflozin 15 mg (T2DM with Mild Renal Impairment)

Ertugliflozin (15 mg), oral, administered in participants with T2DM and with mild renal impairment

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

Single oral administration of 3 X 5 mg tablets.

Ertugliflozin 15 mg (T2DM with Moderate Renal Impairment)

Ertugliflozin (15 mg), oral, administered in participants with T2DM and with moderate renal impairment

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

Single oral administration of 3 X 5 mg tablets.

Ertugliflozin 15 mg (T2DM with Severe Renal Impairment)

Ertugliflozin (15 mg), oral, administered in participants with T2DM and with severe renal impairment

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

Single oral administration of 3 X 5 mg tablets.

Ertugliflozin, 15 mg (Healthy Part. with Normal Renal Funct.)

Ertugliflozin (15 mg), oral, administered in participants with healthy participants and with normal renal function

Group Type: EXPERIMENTAL

Ertugliflozin

Intervention Type: DRUG

Single oral administration of 3 X 5 mg tablets.

Interventions

Ertugliflozin

Single oral administration of 3 X 5 mg tablets.

Intervention Type: DRUG

Other Intervention Names

MK-8835

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 28703316 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34213819 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33813736 (View on PubMed)

Other Identifiers

B1521023

Identifier Type: OTHER

Identifier Source: secondary_id

MK-8835-009

Identifier Type: OTHER

Identifier Source: secondary_id

8835-009

Identifier Type: -

Identifier Source: org_study_id