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Type 2 Diabetes MellitusPhase 1NCT02115347

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

A Phase 1 study testing Ertugliflozin 15 mg in people with Type 2 Diabetes Mellitus and Hepatic Impairment, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Type 2 Diabetes Mellitus, Hepatic Impairment
What is being tested?
Ertugliflozin 15 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
No sites listed yet
Study dates
19 Sep 2014to 19 Jan 2015
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

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

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).

Being tested
Ertugliflozin 15 mg
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ertugliflozin 15 mgDrug

    Tablet

Study groups in NCT02115347
Study groupRoleWhat they receive
Ertugliflozin 15 mg - Moderate Hepatic ImpairmentExperimentalParticipants receive a single 15 mg oral dose (tablet) of ertugliflozin
Receives: Drug: Ertugliflozin 15 mg
Ertugliflozin 15 mg - Healthy ParticipantsOtherParticipants receive a single 15 mg oral dose (tablet) of ertugliflozin
Receives: Drug: Ertugliflozin 15 mg
Ertugliflozin 15 mg - Mild Hepatic ImpairmentExperimentalParticipants receive a single 15 mg oral dose (tablet) of ertugliflozin
Receives: Drug: Ertugliflozin 15 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. AUC From Hour 0 to Infinity (AUCinf) for Ertugliflozin

    Area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf).

    Measured: 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)
  1. 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).

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

  2. 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).

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

  3. Maximum Plasma Concentration (Cmax) of Ertugliflozin

    Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

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

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

    Maximum plasma concentration for unbound drug (ertugliflozin only).

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

  5. 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.

    Measured: Up to 19 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2014 (estimated)
  2. Study start19 Sep 2014
  3. Primary completion10 Jan 2015
  4. Study completion19 Jan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02115347
Sponsor's protocol ID
8835-014
Other IDs
MK-8835-014, B1521024
Status last verified
Aug 2018
First submitted
14 Apr 2014
Last updated
20 Aug 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 33813736
  • 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.

    PubMed 30224193

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ertugliflozin 15 mg in people with Type 2 Diabetes Mellitus and Hepatic Impairment, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02115347, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2018.

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