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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 1, Non-randomized, Open-label, Single Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Subjects With Hepatic Impairment and the Healthy Subjects With Normal Hepatic Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02115347
• Other study ID #: 8835-014
• Secondary ID: MK-8835-014B1521
• Status: Completed
• Phase: Phase 1
• Start date: September 19, 2014
• Est. completion date: January 19, 2015

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 19, 2015
• Est. primary completion date: January 10, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hepatic Impairment
• Liver Diseases
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ertugliflozin 15 mg
Tablet

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Pfizer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin	Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (AUClast).	Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Primary	AUC From Hour 0 to Infinity (AUCinf) for Ertugliflozin	Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf).	Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Secondary	AUClast for Fraction of Ertugliflozin Unbound in Plasma (AUClast,u)	Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) for unbound drug (ertugliflozin only).	Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Secondary	AUCinf for Fraction of Ertugliflozin Unbound in Plasma (AUCinf,u)	Area under the plasma concentration-time profile from time zero extrapolated to infinite time for unbound drug (ertugliflozin only) (AUCinf, u).	Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Secondary	Maximum Plasma Concentration (Cmax) of Ertugliflozin	Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.	Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Secondary	Cmax for Fraction of Ertugliflozin Unbound in Plasma (Cmax,u)	Maximum plasma concentration for unbound drug (ertugliflozin only).	Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours
Secondary	Number of Participants Who Experienced an Adverse Event	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to 19 days