Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014)
Condition: Type 2 Diabetes Mellitus; Hepatic Impairment
MeSH terms: Liver Diseases; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin 15 mg
Intervention description: Tablet
Intervention MeSH terms: Ertugliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

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