Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment; Type 2 Diabetes Mellitus

Treatments: Drug: Ertugliflozin 15 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02115347

8835-014

B1521024 (Other Identifier)

MK-8835-014 (Other Identifier)

Details and patient eligibility

About

This is a study to assess the pharmacokinetics and safety of ertugliflozin (MK-8835, PF-04971729) in participants with hepatic impairment versus healthy participants. In Part 1 of the study, participants with moderate hepatic impairment (Child-Pugh score 7-9) and matched healthy participants will be enrolled; depending on results in Part 1, Part 2 may be conducted and will enroll participants with mild hepatic impairment (Child-Pugh score 5-6).

Enrollment: 16 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

ALL PARTICIPANTS:

• Body Mass Index (BMI) of 18 to 40 kg/m^2; and a total body weight >50 kg (110 lbs)
• Male or female not of reproductive potential
• If a female of reproductive potential, agrees to remain abstinent from heterosexual activity or agree to use or have their partner use 2 methods of acceptable contraception to prevent pregnancy while the participant is receiving study medication and for 14 days after the last dose of study medication PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
• Healthy with normal hepatic function PARTICIPANTS WITH HEPATIC IMPAIRMENT
• Satisfy the criteria for Child-Pugh classification [moderate (Part 1): Child-Pugh Scores 7-9 points, mild (Part 2): Child-Pugh Scores 5-6 points] within 14 days before administration of study medication
• A diagnosis of hepatic impairment due to primary liver disease and not secondary to other diseases
• Stable hepatic impairment, defined as no clinically-significant change in disease status within the last 30 days
• On a stable dose of medication and/or treatment regimen used to manage hepatic disease for at least 4 weeks prior to study start

Exclusion criteria

ALL PARTICIPANTS

• A known hypersensitivity or intolerance to ertugliflozin or any other Sodium-Glucose co-Transporter 2 (SGLT2) inhibitor (i.e., canagliflozin [Invokana], dapagliflozin [Farxiga], empagliflozin, or ipragliflozin)
• Febrile illness within 5 days prior to the first dose of study medication
• Any clinically significant malabsorption condition
• A positive urine drug screen for drugs of abuse or recreational drugs
• Abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of study start
• Treatment with an investigational drug within 30 days preceding the first dose of study medication
• Pregnant or breastfeeding females
• Use of herbal supplements within 28 days prior to the first dose of study medication
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing
• History of sensitivity to heparin or heparin-induced thrombocytopenia PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
• Use of prescription drugs (hormonal methods of birth control are allowed), vitamins, and dietary supplements within 7 days prior to the first dose of study medication
• Positive serology for Hepatitis B or C PARTICIPANTS WITH HEPATIC IMPAIRMENT
• Hepatic carcinoma and hepatorenal syndrome or life expectancy less than 1 year
• Undergone portal-caval shunt surgery
• History of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 1 month prior to study entry
• Signs of significant hepatic encephalopathy
• Severe ascites and/or pleural effusion
• A transplanted kidney, heart or liver
• Received any of the following medications within 7 days prior to the first dose of study medication or during the study: other SGLT2 inhibitors (eg, dapagliflozin, canagliflozin, empagliflozin, and ipragliflozin); any potent drug-metabolizing enzyme-inducing drug, including rifampin, phenytoin, and carbamazepine; probenecid, valproic acid, gemfibrozil

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

Ertugliflozin 15 mg - Moderate Hepatic Impairment

Experimental group

Description:

Participants receive a single 15 mg oral dose (tablet) of ertugliflozin

Treatment:

Drug: Ertugliflozin 15 mg

Ertugliflozin 15 mg - Healthy Participants

Other group

Description:

Participants receive a single 15 mg oral dose (tablet) of ertugliflozin

Treatment:

Drug: Ertugliflozin 15 mg

Ertugliflozin 15 mg - Mild Hepatic Impairment

Experimental group

Description:

Participants receive a single 15 mg oral dose (tablet) of ertugliflozin

Treatment:

Drug: Ertugliflozin 15 mg