pharmacokinetics, safety, and tolerability of ertugliflozin (mk-8835/pf-04971729) in participants with hepatic impairment and in healthy participants (mk-8835-014)

Conditions: Type 2 Diabetes Mellitus; Hepatic Impairment

Summary: 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).


Eligibility criteria:
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