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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Renal Impairment; Type 2 Diabetes Mellitus

Treatments: Drug: Ertugliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01948986

MK-8835-009 (Other Identifier)

8835-009

B1521023 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

36 participants in 5 patient groups

Ertugliflozin 15 mg (T2DM with Normal Renal Function)

Experimental group

Description:

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

Treatment:

Drug: Ertugliflozin

Ertugliflozin 15 mg (T2DM with Mild Renal Impairment)

Experimental group

Description:

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

Treatment:

Drug: Ertugliflozin

Ertugliflozin 15 mg (T2DM with Moderate Renal Impairment)

Experimental group

Description:

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

Treatment:

Drug: Ertugliflozin

Ertugliflozin 15 mg (T2DM with Severe Renal Impairment)

Experimental group

Description:

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

Treatment:

Drug: Ertugliflozin

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

Experimental group

Description:

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

Treatment:

Drug: Ertugliflozin