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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02115347
First received: April 14, 2014
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ertugliflozin 15 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of participants who experienced an adverse event [ Time Frame: Up to 19 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: July 2014
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertugliflozin 15 mg - Moderate Hepatic Impairment
Participants receive a single 15 mg oral dose of ertugliflozin
Drug: Ertugliflozin 15 mg
Ertugliflozin 15 mg - Healthy Participants
Participants receive a single 15 mg oral dose of ertugliflozin
Drug: Ertugliflozin 15 mg
Experimental: Ertugliflozin 15 mg - Mild Hepatic Impairment
Participants receive a single 15 mg oral dose of ertugliflozin
Drug: Ertugliflozin 15 mg

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 one 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02115347

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
Investigators
Study Director: Medical Director Merck/Pfizer
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02115347     History of Changes
Other Study ID Numbers: 8835-014
Study First Received: April 14, 2014
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 22, 2014