Omarigliptin Add-on to Insulin in Japanese Participants With Type 2 Diabetes Mellitus (T2DM, MK-3102-039)
15 de agosto de 2019 actualizado por: Merck Sharp & Dohme LLC
A Phase IV, Multicenter, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Trial and Subsequent Open-Label, Extension Trial to Assess the Safety and Efficacy of Addition of Omarigliptin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Monotherapy in Addition to Diet and Exercise Therapy
This study will examine the efficacy of omarigliptin 25 mg once weekly compared to placebo in Japanese patients with T2DM who have inadequate glycemic control on insulin monotherapy in addition to diet and exercise therapy.
The primary hypothesis of the study is that omarigliptin 25 mg once weekly provides greater reduction in hemoglobin A1C (HbA1c) compared with placebo as assessed by change from baseline to Week 16 [Phase A (double-blind period)].
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
After a screening period of up to 2 weeks followed by a pretreatment period of 2 or 10 weeks, each participant will be receiving assigned double-blind treatment (omarigliptin 25 mg or placebo once weekly) for approximately 16 weeks (Phase A) followed by 36 weeks of open-label treatment (omarigliptin 25 mg once weekly, Phase B).
After the end of treatment each participant will be followed for 21 days.
Tipo de estudio
Intervencionista
Inscripción (Actual)
184
Fase
- Fase 4
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
20 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Have T2DM
Meet all of following criteria at Week -2 of pre-randomization
- On diet and exercise therapy for 6 weeks or longer, AND
- Have been on a stable dosage and administration of insulin (8 to 40 units/day) for 10 weeks or longer, AND.
- Have not been on any additional anti-hyperglycemic agent (AHAs, except for insulin monotherapy) for 8 weeks or longer, AND
- HbA1c ≥7.5% and ≤10.0%
- Fasting Plasma Glucose (FPG) ≥126 mg/dL and ≤230 mg/dL
- Have a body mass index (BMI) >18 kg/m^2 and <40 kg/m^2
- A male or female not of reproductive potential or a female of reproductive potential and agrees to remain abstinent from heterosexual activity, or agrees to use acceptable contraception to prevent pregnancy.
Exclusion Criteria:
- Has type 1 diabetes mellitus or has a history of diabetic ketoacidosis.
Has a history of being administered any of the following AHAs including fixed dose combination (FDC) containing the following ingredients:
- Thiazolidinediones within 12 weeks
- Glucagon-like peptide 1 (GLP-1) receptor agonists within 12 weeks
- Omarigliptin at any time
- Has history of severe hypoglycemia with coma or loss of consciousness, or for whom hypoglycemia was observed greater or equal to two times per week within 8 weeks
- Is currently participating in or has participated in another study with an investigational compound or device within the prior 12 weeks
- Has undergone a surgical procedure within 8 weeks or has planned major surgery during the study.
- Receives a lipid-lowering medication or thyroid replacement therapy at unstable dosage and administration
- Has poorly controlled hypertension
- Has a medical history of active liver disease, including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
- Has human immunodeficiency virus (HIV).
- Has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder within the past 3 months
- Has severe peripheral vascular disease.
- Has a history of malignancy ≤ 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer:
- Has a clinically important hematological disorder.
- (For women of childbearing potential) has a positive urine pregnancy test.
- Is pregnant or breast feeding
- Is expected to conceive during the study
- Is expected to undergo hormonal therapy in preparation to donate eggs during the study
- Routinely consumes >14 alcoholic drinks per week or engages in binge drinking
- Has donated or plans to donate blood products of >300 mL within 8 weeks or during the study
- Has received or plans to receive blood products within 12 weeks or during the study
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: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Omarigliptin 25 mg
Omarigliptin 25 mg once weekly for 52 weeks (Phase A and B)
|
Omarigliptin, 25 mg orally once weekly
Otros nombres:
Insulin will be administered subcutaneously during the trial as monotherapy; dosage and administration following each package insert.
|
|
Experimental: Placebo→Omarigliptin 25 mg
Placebo to Omarigliptin once weekly for 16 weeks (Phase A) switching to Omarigliptin 25 mg once weekly for 36 weeks (Phase B)
|
Omarigliptin, 25 mg orally once weekly
Otros nombres:
Insulin will be administered subcutaneously during the trial as monotherapy; dosage and administration following each package insert.
Placebo to omarigliptin orally once weekly
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Baseline (Day 1) and Week 16
|
HbA1c is a measure of the percentage of glycated hemoglobin in the blood.
Participant whole blood samples were collected at baseline and Week 16 to determine the Constrained Longitudinal Data Analysis least squares mean HbA1c change from baseline (i.e., HbA1c at Week 16 minus HbA1c at baseline).
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
Negative data values indicated a reduction in HbA1c levels.
|
Baseline (Day 1) and Week 16
|
|
Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Up to Week 16
|
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
|
Up to Week 16
|
|
Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
Periodo de tiempo: Up to Week 52
|
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.
|
Up to Week 52
|
|
Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Up to Week 16
|
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
|
Up to Week 16
|
|
Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
Periodo de tiempo: Up to Week 52
|
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.
|
Up to Week 52
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Baseline (Day 1) and Week 16
|
Blood glucose was measured on a fasting basis.
FPG is expressed as mg/dL.
Blood was drawn at predose on Day 1 and after 16 weeks of treatment to determine Constrained Longitudinal Data Analysis change in plasma glucose levels (i.e., FPG at Week 16 minus FPG at baseline).
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
Negative data values indicated a reduction in FPG levels.
|
Baseline (Day 1) and Week 16
|
|
Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Week 16
|
HbA1c is a measure of the percentage of glycated hemoglobin in the blood.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
Each of the 10 imputed data sets was summarized to obtain the percentage of responders within each group and were combined using standard multiple imputation techniques to yield an overall estimate of response rate and associated variance for each group.
A constrained longitudinal data analysis was used to analyze the data and Wilson score method by treatment groups used for the analysis of percentages of individuals at the HbA1c goals of <7.0% at Week 16 and the 95% confidence intervals (CIs).
Miettinen & Nurminen (M&N) method after imputations were used to calculate the treatment differences of the percentages of individuals and the 95% CIs.
|
Week 16
|
|
Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Week 16
|
HbA1c is a measure of the percentage of glycated hemoglobin in the blood.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
Each of the 10 imputed data sets was summarized to obtain the percentage of responders within each group and were combined using standard multiple imputation techniques to yield an overall estimate of response rate and associated variance for each group.
A constrained longitudinal data analysis was used to analyze the data and Wilson score method by treatment groups used for the analysis of percentages of individuals at the HbA1c goals of <6.5% at Week 16 and the 95% confidence intervals (CIs).
Miettinen & Nurminen (M&N) method after imputations were used to calculate the treatment differences of the percentages of individuals and the 95% CIs.
|
Week 16
|
|
Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
Periodo de tiempo: Baseline (Day 1) and Week 16
|
1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia.
1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Data after glycemic rescue were excluded from this analysis.
Data (1,5-AG at Week 16 minus 1,5-AG at baseline) was analyzed by Constrained Longitudinal Data Analysis.
Positive data values indicate an increase in 1,5-AG levels and correlate with an improvement in glycemia.
|
Baseline (Day 1) and Week 16
|
|
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B)
Periodo de tiempo: Baseline (Day 1) and Week 52
|
HbA1c is a measure of the percentage of glycated hemoglobin in the blood.
Participant whole blood samples were collected at baseline and Week 52 to determine the mean HbA1c change from baseline (i.e., HbA1c at Week 52 minus HbA1c at baseline).
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Negative data values indicated a reduction in HbA1c levels.
|
Baseline (Day 1) and Week 52
|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B)
Periodo de tiempo: Baseline (Day 1) and Week 52
|
Blood glucose was measured on a fasting basis.
FPG is expressed as mg/dL.
Blood was drawn at predose on Day 1 and after 52 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 52 minus FPG at baseline).
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
Negative data values indicated a reduction in FPG levels.
|
Baseline (Day 1) and Week 52
|
|
Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B)
Periodo de tiempo: Week 52
|
HbA1c is a measure of the percentage of glycated hemoglobin in the blood.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
For the HbA1c goals of <7.0% at Week 52, the percentage of participants and the 95% confidence intervals were calculated using Wilson score method by treatment groups of the double-blind period.
|
Week 52
|
|
Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B)
Periodo de tiempo: Week 52
|
HbA1c is a measure of the percentage of glycated hemoglobin in the blood.
Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control.
For the HbA1c goals of <6.5% at Week 52, the percentage of participants and the 95% confidence intervals were calculated using Wilson score method by treatment groups of the double-blind period.
|
Week 52
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
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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 octubre de 2016
Finalización primaria (Actual)
21 de agosto de 2018
Finalización del estudio (Actual)
21 de agosto de 2018
Fechas de registro del estudio
Enviado por primera vez
15 de septiembre de 2016
Primero enviado que cumplió con los criterios de control de calidad
15 de septiembre de 2016
Publicado por primera vez (Estimar)
20 de septiembre de 2016
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
19 de septiembre de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
15 de agosto de 2019
Última verificación
1 de agosto de 2019
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 3102-039
- MK-3102-039 (Otro identificador: Merck Protocol Number)
- 163455 (Identificador de registro: JAPIC-CTI)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Sí
Descripción del plan IPD
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .