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Trial record 1 of 1 for:    NCT02115347
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Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014)

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ClinicalTrials.gov Identifier: NCT02115347
Recruitment Status : Completed
First Posted : April 16, 2014
Results First Posted : August 3, 2018
Last Update Posted : August 20, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE April 14, 2014
First Posted Date  ICMJE April 16, 2014
Results First Submitted Date  ICMJE November 1, 2017
Results First Posted Date  ICMJE August 3, 2018
Last Update Posted Date August 20, 2018
Actual Study Start Date  ICMJE September 19, 2014
Actual Primary Completion Date January 10, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2017)
  • Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin [ Time Frame: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
    Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (AUClast).
  • AUC From Hour 0 to Infinity (AUCinf) for Ertugliflozin [ Time Frame: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
    Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf).
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2014)
  • Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin [ Time Frame: Hour 0 (predose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
  • AUC From Hour 0 to Infinity (AUCinf) for Ertugliflozin [ Time Frame: Hour 0 (predose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2017)
  • AUClast for Fraction of Ertugliflozin Unbound in Plasma (AUClast,u) [ Time Frame: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
    Area under the plasma concentration-time profile from time zero to time of the last quantifiable concentration (Clast) for unbound drug (ertugliflozin only).
  • AUCinf for Fraction of Ertugliflozin Unbound in Plasma (AUCinf,u) [ Time Frame: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
    Area under the plasma concentration-time profile from time zero extrapolated to infinite time for unbound drug (ertugliflozin only) (AUCinf, u).
  • Maximum Plasma Concentration (Cmax) of Ertugliflozin [ Time Frame: Hour 0 (predose), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
    Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
  • Cmax for Fraction of Ertugliflozin Unbound in Plasma (Cmax,u) [ Time Frame: 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 for unbound drug (ertugliflozin only).
  • Number of Participants Who Experienced an Adverse Event [ Time Frame: Up to 19 days ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2014)
  • AUClast for Fraction of Ertugliflozin Unbound in Plasma (AUClast,u) [ Time Frame: Hour 0 (predose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
  • AUCinf for Fraction of Ertugliflozin Unbound in Plasma (AUCinf,u) [ Time Frame: Hour 0 (predose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
  • Maximum Plasma Concentration (Cmax) of Ertugliflozin [ Time Frame: Hour 0 (predose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
  • Cmax for Fraction of Ertugliflozin Unbound in Plasma (Cmax,u) [ Time Frame: Hour 0 (predose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours ]
  • Number of Participants Who Experienced an Adverse Event [ Time Frame: Up to 19 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics, Safety, and Tolerability of Ertugliflozin (MK-8835/PF-04971729) in Participants With Hepatic Impairment and in Healthy Participants (MK-8835-014)
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 2 Diabetes Mellitus
  • Hepatic Impairment
Intervention  ICMJE Drug: Ertugliflozin 15 mg
Tablet
Study Arms  ICMJE
  • Experimental: Ertugliflozin 15 mg - Moderate Hepatic Impairment
    Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
    Intervention: Drug: Ertugliflozin 15 mg
  • Ertugliflozin 15 mg - Healthy Participants
    Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
    Intervention: Drug: Ertugliflozin 15 mg
  • Experimental: Ertugliflozin 15 mg - Mild Hepatic Impairment
    Participants receive a single 15 mg oral dose (tablet) of ertugliflozin
    Intervention: Drug: Ertugliflozin 15 mg
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 15, 2015)
16
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2014)
24
Actual Study Completion Date  ICMJE January 19, 2015
Actual Primary Completion Date January 10, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02115347
Other Study ID Numbers  ICMJE 8835-014
MK-8835-014 ( Other Identifier: Merck Study number )
B1521024 ( Other Identifier: Pfizer Study number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director: Medical Director Merck/Pfizer
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP