Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)
8 november 2019 bijgewerkt door: Merck Sharp & Dohme LLC
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, 2-Period, Cross-Over Single Day Evaluation Of The Pharmacokinetic-Pharmacodynamic Effect Of Once And Twice Daily Oral Administration Of PF-04971729 In Patients With Type 2 Diabetes Mellitus
This is a Phase 1 randomized, double-blind, sponsor open, 4 arm, 2 way cross-over study using 2 cohorts.
The objective of the study is to evaluate the pharmacodynamics (PD) effects and the pharmacokinetic (PK) of single day dosing of 2 mg and 4 mg doses of ertugliflozin (Ertu, PF-04971729/MK-8835) each administered once vs twice daily (morning [AM] and evening [PM]) in adults with type 2 diabetes.
Studie Overzicht
Toestand
Voltooid
Conditie
Studietype
Ingrijpend
Inschrijving (Werkelijk)
52
Fase
- Fase 1
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 65 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Participants with type 2 diabetes mellitus, either treatment-naïve or on up to 2 acceptable oral anti-diabetes drugs for at least 8-weeks prior to study.
Exclusion Criteria:
- Participants with type 1 diabetes mellitus, participants with stroke, unstable angina, heart attack in last 6-months, uncontrolled blood pressure.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Ander
- Toewijzing: Gerandomiseerd
- Interventioneel model: Crossover-opdracht
- Masker: Dubbele
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Cohort 1: Ertu 2 mg/Placebo (Pbo)→Ertu 1 mg/Ertu 1 mg
Period 1: Ertu 2 mg in the AM and Pbo in the PM for 1 day.
Period 2: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day.
There was a >= 7 day washout period between Period 1 and Period 2.
|
Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose
Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day
Placebo to ertugliflozin administered as a single dose
|
|
Experimenteel: Cohort 1: Ertu 1 mg/Ertu 1 mg→Ertu 2 mg/Pbo
Period 1: Ertu 1 mg in the AM and Ertu 1 mg in the PM for 1 day.
Period 2: Ertu 2 mg in the AM and Pbo in the PM for 1 day.
There was a >= 7 day washout period between Period 1 and Period 2.
|
Ertugliflozin 2 mg dose (two 1 mg strength tablets), administered as a single dose
Ertugliflozin 1 mg dose (1 mg strength tablet) administered twice daily x 1 day
Placebo to ertugliflozin administered as a single dose
|
|
Experimenteel: Cohort 2: Ertu 4 mg/Pbo→Ertu 2 mg/Ertu 2 mg
Period 1: Ertu 4 mg in the AM and Pbo in the PM for 1 day.
Period 2: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day.
There was a >= 7 day washout period between Period 1 and Period 2.
|
Placebo to ertugliflozin administered as a single dose
Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose
Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day
|
|
Experimenteel: Cohort 2: Ertu 2 mg/Ertu 2 mg→Ertu 4 mg/Pbo
Period 1: Ertu 2 mg in the AM and Ertu 2 mg in the PM for 1 day.
Period 2: Ertu 4 mg in the AM and Pbo in the PM for 1 day.
There was a >= 7 day washout period between Period 1 and Period 2.
|
Placebo to ertugliflozin administered as a single dose
Ertugliflozin 4 mg dose (four 1 mg strength tablets), administered as a single dose
Ertugliflozin 2 mg dose (two 1 mg strength tablets) administered twice daily x 1 day
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Cumulative Urinary Glucose Excretion Over 0 to 24 Hours
Tijdsspanne: 0 to 24 hours after the morning dose
|
Urine for analysis of glucose was collected at prespecified intervals.
Each participant emptied his/her bladder just before dosing, and the collection started after the morning dose (collection times: 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after the morning dose).
The average amount of urinary glucose excreted from 0 to 24 hours after the morning dose is presented in the table below.
|
0 to 24 hours after the morning dose
|
|
Urinary Glucose Excretion by Time Period
Tijdsspanne: At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)
|
Urine for analysis of glucose was collected at prespecified intervals.
Each participant emptied his/her bladder just before dosing, and the collection started after the morning dose (collection times: 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 hours after the morning dose).
The average amount of urinary glucose excreted during the pre-specified time frame is presented in the table below.
|
At 0-4 hrs, 4-8 hrs, 8-12 hrs, and 12-24 hrs after the AM dose (up to 24 hours)
|
|
24-hour Weighted Mean Plasma Glucose
Tijdsspanne: Up to 24 hours
|
Blood was collected during each treatment period at pre-dose (fasted) on Day 1 (Hour 0) and post-dose (fed) on Day 1 at 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 12.5, 13, 14, 15, 16, 18, and 24 hours.
|
Up to 24 hours
|
|
Weighted Mean Postprandial Plasma Glucose
Tijdsspanne: At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)
|
The weighted mean postprandial glucose over the specified intervals were analyzed by cohort.
|
At 0-5 hours, 5-12 hrs, and 12-18 hrs after the morning dose (up to 18 hours)
|
|
Fasting Plasma Glucose
Tijdsspanne: Up to 24 hours
|
Blood samples were to be collected following a fast from all food and drink (except water) for at least 8 hours.
Fasting Plasma Glucose was collected as part of the assessment of weighted mean 24-hour plasma glucose.
As such, it was not specified as an endpoint in the Statistical Analysis Plan and was not analyzed or summarized separately.
|
Up to 24 hours
|
|
Fasting C-peptide
Tijdsspanne: Up to 24 hours (0 and 24 hours)
|
The fasting c-peptide was analyzed by cohort using a mixed-effects model with sequence, period, and treatment as fixed effects and participant within sequence as a random effect.
|
Up to 24 hours (0 and 24 hours)
|
|
Number of Participants Experiencing an Adverse Event
Tijdsspanne: Up to 16 days
|
An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device.
The table below includes all data collected since the first dose of study drug.
|
Up to 16 days
|
|
Number of Participants Discontinuing Study Drug Due to an Adverse Event
Tijdsspanne: Up to 8 days (Day 1 in each dosing period)
|
An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device.
The table below includes all data collected since the first dose of study drug.
Data include participants discontinued due to adverse events, participants with dose reduced or temporary discontinuation due to adverse events.
|
Up to 8 days (Day 1 in each dosing period)
|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUClast) for Ertugliflozin
Tijdsspanne: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
|
Pharmacokinetic (PK) parameter of AUClast for study drug.
Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
|
0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
|
|
Maximum Plasma Concentration (Cmax) of Ertugliflozin
Tijdsspanne: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
|
PK parameter of Cmax for study drug.
Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
|
0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
|
|
Time Taken to Reach the Maximum Observed Plasma Concentration (Tmax) of Ertugliflozin
Tijdsspanne: 0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
|
PK parameter of Tmax for study drug.
Actual sample collection times (relative to the AM dose) were used for the pharmacokinetic analysis.
|
0 predose, 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 10, 12, 18, 24 hours postdose
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Medewerkers
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- 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.
- Dawra VK, Liang Y, Shi H, Bass A, Hickman A, Terra SG, Zhou S, Cutler D, Sahasrabudhe V. A PK/PD study comparing twice-daily to once-daily dosing regimens of ertugliflozin in healthy subjects . Int J Clin Pharmacol Ther. 2019 Apr;57(4):207-216. doi: 10.5414/CP203343.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
17 februari 2010
Primaire voltooiing (Werkelijk)
7 april 2010
Studie voltooiing (Werkelijk)
7 april 2010
Studieregistratiedata
Eerst ingediend
20 januari 2010
Eerst ingediend dat voldeed aan de QC-criteria
20 januari 2010
Eerst geplaatst (Schatting)
22 januari 2010
Updates van studierecords
Laatste update geplaatst (Werkelijk)
21 november 2019
Laatste update ingediend die voldeed aan QC-criteria
8 november 2019
Laatst geverifieerd
1 november 2019
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 8835-040
- B1521007 (Andere identificatie: Pfizer Protocol Number)
- MK-8835-040 (Andere identificatie: Merck Protocol Number)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
JA
Beschrijving IPD-plan
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .