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Diabetes Mellitus, Type 2Phase 1NCT01223339

Evaluation of Pharmacokinetics, Safety, And Tolerability Of Ertugliflozin (PF-04971729, MK-8835) In Japanese And Western Healthy Participants (MK-8835-041)

A Phase 1 study testing Ertugliflozin in people with Diabetes Mellitus, Type 2, 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 study is to characterize the pharmacokinetics, safety, tolerability, and pharmacodynamics of single and multiple oral doses (SD, MD) of ertugliflozin (PF-04971729, MK-8835) in Japanese healthy participants. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Ertugliflozin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
24 participants
Where
No sites listed yet
Study dates
Oct 2010to Feb 2011
Phase
Phase 1
Are there results?
None posted in the registry

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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy male and/or female subjects of non-childbearing potential, between the ages of 18 and 55 years, inclusive
  • Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
  • Japanese subjects must have four Japanese grandparents who were born in Japan.
  • Mean body weight and the body weight range of Western subjects are similar to those of Japanese subjects with a 10% plus and minus error.
  • An informed consent document signed and dated by the subject.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan,laboratory tests, and other study procedures.

Who cannot join

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
  • Asian or Polynesian subjects in Western subject groups.
  • Any condition possibly affecting drug absorption (eg, gastrectomy).
  • A positive urine drug screen.
  • History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males within 6 months of screening.
  • History or evidence of habitual use of tobacco or nicotine containing products within 3 months of Screening, with the exception of light smoking (up to 5 cigarettes per day or the equivalent).
Show all 13Show fewer
  • Treatment with an investigational drug within 30 days or 5 half-lives preceding the first dose of study medication.
  • 12-lead ECG demonstrating QTc >450 msec at screening.
  • Subjects with ANY of the following abnormalities on safety laboratory tests):
  • Evidence of glycosuria, as defined by a positive urine dipstick test;
  • Fasting serum triglyceride >300 mg/dL;
  • Fasting LDL-cholesterol > than or equal to 190 mg/dL.
  • Fasting serum glucose >125 mg/dL.

About this study

Official title: A Phase 1, Randomized, Double Blind, Placebo-Controlled, Parallel Cohort, Single Dose Escalation And Multiple Dose Study In Japanese Healthy Subjects, And Open Label, Single Dose Escalation Study In Western Healthy Subjects To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-04971729

This study is to characterize the pharmacokinetics, safety, tolerability, and pharmacodynamics of single and multiple oral doses (SD, MD) of ertugliflozin (PF-04971729, MK-8835) in Japanese healthy participants. The secondary objective is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of ertugliflozin in Western healthy participants as compared to Japanese healthy participants.

Being tested
Ertugliflozin, Placebo
Keywords
Ertugliflozin, Japanese and Western population, pharmacokinetics, pharmacodynamics
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.

  • ErtugliflozinDrug

    Dose escalation of 1, 5, and 25 mg Ertugliflozin administered in the fasted state

  • PlaceboDrug

    Placebo tablets to Ertugliflozin administered in the fasted state

  • ErtugliflozinDrug

    Ertugliflozin 25 mg tablets administered once daily in the fed state for 7 days

  • PlaceboDrug

    Placebo tablets administered once daily in the fed state for 7 days

Study groups in NCT01223339
Study groupRoleWhat they receive
Single Dose Japanese CohortExperimentalThis will be a single dose Cohort in which Japanese healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin or placebo through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration.
Receives: Drug: Ertugliflozin; Drug: Placebo
Single dose Western cohortExperimentalThis will be a single dose Cohort in which Western healthy participants will receive 3 ascending single doses (1 mg, 5 mg, and 25 mg) of ertugliflozin through 3 dosing periods. A minimum wash out period of 7-days will be set between each dose administration.
Receives: Drug: Ertugliflozin
Multiple Dose Japanese CohortExperimentalThis will be a multiple dose Cohort in which Japanese healthy participants will receive once-daily 25 mg ertugliflozin or placebo for 7 days.
Receives: Drug: Ertugliflozin; Drug: Placebo

What is being measured

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

  1. Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  2. Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  3. Area under the plasma concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  4. AUC from Hour 0 to infinity (AUCinf) for ertugliflozin for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  5. Ertugliflozin half life (t1/2) for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  6. Apparent clearance (CL/F) of ertugliflozin for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  7. Apparent volume of distribution (Vz/F) for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  8. Accumulation Ratio of Area Under the Curve for the dosing interval of ertugliflozin (Rac) for the Single Dose Cohort

    Measured: Up to Day 4 of each treatment period

  9. Number of participants who experienced an adverse event (AE) for the Single Dose Cohort

    Measured: Up to 10 days after the final dose of study drug (Up to Day 11)

  10. Number of participants who discontinued study drug due to an AE for the Single Dose Cohort

    Measured: Up to Day 1 of each treatment period

  11. Urinary Glucose Excretion over 24 hours for the Single Dose Cohort

    Measured: Up to 24 hours postdose (Up to Day 2)

  12. Cmax of ertugliflozin for the Multiple Dose Cohort

    Measured: Up to Day 10

  13. Tmax of ertugliflozin for the Multiple Dose Cohort

    Measured: Up to Day 10

  14. AUClast for ertugliflozin for the Multiple Dose Cohort

    Measured: Up to Day 10

  15. AUCinf for ertugliflozin for the Multiple Dose Cohort

    Measured: Up to Day 10

  16. t1/2 for the Multiple Dose Cohort

    Measured: Up to Day 10

  17. CL/F of ertugliflozin for the Multiple Dose Cohort

    Measured: Up to Day 10

  18. Vz/F for the Multiple Dose Cohort

    Measured: Up to Day 10

  19. Rac for the Single Dose Cohort

    Measured: Up to Day 10

  20. Number of participants who experienced an AE for the Multiple Dose Cohort

    Measured: Up to 10 days after the final dose of study drug (Up to Day 17)

  21. Number of participants who discontinued study drug due to an AE for the Multiple Dose Cohort

    Measured: Up to Day 7

  22. Urinary Glucose Excretion over 24 hours for the Multiple Dose Cohort

    Measured: Up to 24 hours postdose (Up to Day 8)

Timeline

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

  1. First posted19 Oct 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionFeb 2011
  4. Study completionFeb 2011

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
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01223339
Sponsor's protocol ID
8835-041
Status last verified
May 2016
First submitted
13 Oct 2010
Last updated
20 May 2016
Results posted
No
Data monitoring committee
No

Publications

  • Fediuk DJ, Sahasrabudhe V, Dawra VK, Zhou S, Sweeney K. Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1297-1306. doi: 10.1002/cpdd.970. Epub 2021 Jul 2.

    PubMed 34213819

  • 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

  • Li Y, Nucci G, Yamamoto Y, Fediuk DJ, Sahasrabudhe V. Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Healthy Japanese and Western Subjects. Clin Pharmacol Drug Dev. 2021 Jul;10(7):765-776. doi: 10.1002/cpdd.908. Epub 2021 Jan 12.

    PubMed 33434408

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ertugliflozin in people with Diabetes Mellitus, Type 2, 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 6 inclusion and 13 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 May 2016. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum plasma concentration (Cmax) of ertugliflozin for the Single Dose Cohort (time frame: Up to Day 4 of each treatment period). The study lists 22 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 NCT01223339, which also lists 3 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 May 2016.

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