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

NCT02115347 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 8835-014MK-8835-014B1521024
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• AUClast for Fraction of Ertugliflozin Unbound in Plasma (AUClast,u)

  Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours

• AUCinf for Fraction of Ertugliflozin Unbound in Plasma (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

• Maximum Plasma Concentration (Cmax) of Ertugliflozin

  Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours

• Cmax for Fraction of Ertugliflozin Unbound in Plasma (Cmax,u)

  Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours

• Number of Participants Who Experienced an Adverse Event

  Up to 19 days

Study Arms (3)

Ertugliflozin 15 mg - Moderate Hepatic Impairment

EXPERIMENTAL

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

Drug: Ertugliflozin 15 mg

Ertugliflozin 15 mg - Healthy Participants

OTHER

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

Drug: Ertugliflozin 15 mg

Ertugliflozin 15 mg - Mild Hepatic Impairment

EXPERIMENTAL

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

Drug: Ertugliflozin 15 mg

Interventions

Ertugliflozin 15 mg DRUG

Tablet

Ertugliflozin 15 mg - Healthy Participants; Ertugliflozin 15 mg - Mild Hepatic Impairment; Ertugliflozin 15 mg - Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Pfizer: collaborator

Related Publications (2)

• 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.

  PMID: 33813736 DERIVED

• 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.

  PMID: 30224193 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

ertugliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck/Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: September 19, 2014
• Primary Completion: January 10, 2015
• Study Completion: January 19, 2015
• Last Updated: August 20, 2018
• Results First Posted: August 3, 2018

Record last verified: 2018-08