Effects of Once and Twice Daily Dosing Regimen of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes (MK-8835-040)
8 de noviembre de 2019 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Tipo de estudio
Intervencionista
Inscripción (Actual)
52
Fase
- Fase 1
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 65 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 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
|
|
Experimental: 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
|
|
Experimental: 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
|
|
Experimental: 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
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Cumulative Urinary Glucose Excretion Over 0 to 24 Hours
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de febrero de 2010
Finalización primaria (Actual)
7 de abril de 2010
Finalización del estudio (Actual)
7 de abril de 2010
Fechas de registro del estudio
Enviado por primera vez
20 de enero de 2010
Primero enviado que cumplió con los criterios de control de calidad
20 de enero de 2010
Publicado por primera vez (Estimar)
22 de enero de 2010
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
21 de noviembre de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
8 de noviembre de 2019
Última verificación
1 de noviembre de 2019
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Trastornos del metabolismo de la glucosa
- Enfermedades metabólicas
- Enfermedades del sistema endocrino
- Diabetes mellitus
- Diabetes Mellitus, Tipo 2
- Agentes hipoglucemiantes
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores del transportador de sodio-glucosa 2
- Ertugliflozina
Otros números de identificación del estudio
- 8835-040
- B1521007 (Otro identificador: Pfizer Protocol Number)
- MK-8835-040 (Otro identificador: Merck Protocol Number)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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