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

• Status: Completed
• Trial end date: 2015-01-19
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Collaborator: Pfizer
• Treatments: Ertugliflozin

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