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

NCT ID: NCT02115347

Last Updated: 2018-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-19
• Study Completion Date: 2015-01-19

Brief 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).

Conditions

Type 2 Diabetes Mellitus; Hepatic Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ertugliflozin 15 mg - Moderate Hepatic Impairment

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

Group Type: EXPERIMENTAL

Ertugliflozin 15 mg

Intervention Type: DRUG

Tablet

Ertugliflozin 15 mg - Healthy Participants

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

Group Type: OTHER

Ertugliflozin 15 mg

Intervention Type: DRUG

Tablet

Ertugliflozin 15 mg - Mild Hepatic Impairment

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

Group Type: EXPERIMENTAL

Ertugliflozin 15 mg

Intervention Type: DRUG

Tablet

Interventions

Ertugliflozin 15 mg

Tablet

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck/Pfizer

References

Marshall JC, Liang Y, Sahasrabudhe V, Tensfeldt T, Fediuk DJ, Zhou S, Krishna R, Dawra VK, Wood LS, Sweeney K. Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure. J Clin Pharmacol. 2021 Sep;61(9):1220-1231. doi: 10.1002/jcph.1866. Epub 2021 Jun 19.

Reference Type: DERIVED

PMID: 33813736 (View on PubMed)

Sahasrabudhe V, Terra SG, Hickman A, Saur D, Raje S, Shi H, Matschke K, Zhou S, Cutler DL. Pharmacokinetics of Single-dose Ertugliflozin in Patients With Hepatic Impairment. Clin Ther. 2018 Oct;40(10):1701-1710. doi: 10.1016/j.clinthera.2018.06.015. Epub 2018 Sep 14.

Reference Type: DERIVED

PMID: 30224193 (View on PubMed)

Other Identifiers

MK-8835-014

Identifier Type: OTHER

Identifier Source: secondary_id

B1521024

Identifier Type: OTHER

Identifier Source: secondary_id

8835-014

Identifier Type: -

Identifier Source: org_study_id