E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus |
Diabetes mellitus de tipo 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes Mellitus |
Diabetes mellitus de tipo 2 |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- After 24 weeks, to assess the effect of the addition of treatment with MK- 3102 compared to placebo on A1C.
- To assess the safety and tolerability of MK-3102. |
- Al cabo de 24 semanas, evaluar el efecto de la adición del tratamiento con MK-3102, en comparación con placebo, sobre la A1C.
- Evaluar la seguridad y la tolerabilidad del MK-3102. |
|
E.2.2 | Secondary objectives of the trial |
- After 24 weeks, to assess the effect of the addition of treatment with MK-3102 compared to placebo on 2-hour post-meal glucose (2-hour PMG) after a standard meal challenge.
- After 24 weeks, to assess the effect of the addition of treatment with MK-3102 compared to placebo on fasting plasma glucose (FPG).
- After 104 weeks, to assess the effect of the addition of treatment with MK-3102 on (1) A1C; (2) FPG; and (3) the durability of glycemic efficacy. |
- Al cabo de 24 semanas, evaluar el efecto de la adición del tratamiento con MK-3102, en comparación con placebo, sobre la glucosa posprandial a las dos horas (GPP tras 2 horas) de la administración de una comida estándar. -Al cabo de 24 semanas, evaluar el efecto de la adición del tratamiento con MK-3102, en comparación con placebo, sobre la glucosa plasmática en ayunas (GPA). - Al cabo de 104 semanas, evaluar el efecto de la adición del tratamiento con MK-3102 sobre (1) la A1C, (2) la GPA y (3) la durabilidad de la eficacia del control glucémico. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has T2DM, and must be ?18 years of age on the day of signing the informed consent form. Note: For India only: Subject has T2DM and is ?18 and ?65 years of age on day of signing informed consent. 2. Subject is on metformin monotherapy at a stable dose of metformin (?1500 mg/day) for at least 12 weeks and has an A1C ?7% and ?10.5%. 3. Subject meets one of the following criteria: a. Subject is a male b. Subject is a female not of reproductive potential defined as one who has either reached natural menopause (defined as ?12 months of spontaneous amenorrhea in women >45 years of age, or ?6 months of spontaneous amenorrhea with serum FSH levels in the postmenopausal range as determined by the laboratory), or had bilateral oophorectomy and/or hysterectomy, or had bilateral tubal ligation at least 6 weeks prior to screening c. Subject is a female of reproductive potential and: 1) Agrees to remain abstinent from heterosexual activity (this form of birth control must be accepted by local regulatory agencies and review committees as the sole method of birth control). OR 2) Agrees to use (or her partner to use) adequate contraception to prevent pregnancy within the projected duration of the trial and for 21 days after the last dose of blinded study medication. Adequate methods of contraception include: - Use of 2 barrier methods. Acceptable barrier methods include diaphragm with spermicide, cervical cap, contraceptive sponge, and condom. - Use of an intrauterine device (IUD) and one of the barrier methods identified above. - Use of an appropriate hormonal contraception and one of the barrier methods identified above. Appropriate hormonal contraceptives include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine and intramuscular agents, and cutaneous patch. - Vasectomy and a single barrier method. 4. Subject understands the trial procedures, alternative treatments available, and risks involved with the trial, and voluntarily agrees to participate by giving written informed consent. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 5. Subject has 100% compliance with MK-3102 placebo treatment during the single blind run-in period (as determined by site-performed capsule count). |
1. El sujeto tiene DMT2 y >/=18 años de edad el día de la firma del documento de consentimiento informado. Nota: En la India solamente: El sujeto tiene DMT2 y >/=18 pero </=65 años de edad el día de la firma del documento de consentimiento informado. 2. El sujeto recibe metformina en monoterapia en una dosis estable (>/=1500 mg/día) desde hace por lo menos 12 semanas y presenta una A1C >/=7 % y </=10,5 %. 3. El sujeto cumple por lo menos uno de los siguientes criterios: a. El sujeto es un varón. b. La sujeto es una mujer sin potencial reproductor que, por definición, es aquella que o ha alcanzado la menopausia natural (que se define como >/=12 meses de amenorrea espontánea en mujeres >45 años de edad, o >/= 6 meses de amenorrea espontánea con concentraciones séricas de FSH en el intervalo posmenopáusico según el laboratorio), o ha sido sometida a ovariectomía bilateral y/o histerectomía, o a ligadura bilateral de trompas como mínimo 6 semanas antes de la selección. c. La sujeto es una mujer con potencial reproductor y: 1) Se compromete a abstenerse de actividad heterosexual (si esta forma de anticoncepción es aceptada por las autoridades sanitarias reguladoras y comités éticos locales como único método anticonceptivo). O BIEN 2) Se compromete a utilizar (o hacer que su pareja utilice) métodos anticonceptivos adecuados para impedir el embarazo dentro de la duración prevista del ensayo y los 21 días siguientes a la última dosis de la medicación enmascarada del estudio. Los métodos anticonceptivos adecuados son: -Uso de dos métodos de barrera. Los métodos aceptables de barrera son: diafragma con espermicida, capuchón cervical, esponja anticonceptiva y preservativo. Uso de un dispositivo intrauterino (DIU) y uno de los métodos de barrera que se han señalado. -Uso de un anticonceptivo hormonal adecuado y uno de los métodos de barrera que se han señalado. Los anticonceptivos hormonales adecuados incluyen todo anticonceptivo registrado y comercializado con estrógeno y/o gestágeno (incluidos productos orales, subcutáneos, intrauterinos, intramusculares y en parches cutáneos). -Vasectomía y un solo método de barrera. 4. El sujeto comprende los procedimientos del ensayo, los tratamientos alternativos disponibles y los riesgos que comporta el ensayo, y otorga voluntariamente su consentimiento para participar mediante su consentimiento informado por escrito. El sujeto también puede otorgar su consentimiento para la futura investigación biomédica. Sin embargo, un sujeto podrá participar en el ensayo principal sin participar en la futura investigación biomédica. 5. El sujeto muestra un cumplimiento del 100 % del tratamiento con placebo de MK-3102 durante el periodo de preinclusión en simple ciego (según el recuento de cápsulas realizado en el centro). |
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E.4 | Principal exclusion criteria |
1. Subject has a history of T1DM or a history of ketoacidosis OR Subject is assessed by the investigator as possibly having T1DM confirmed with a C-peptide <0.7 ng/mL (0.23 nmol/L). 2. Subject has been treated with any AHA therapies other than the protocol-required metformin within the prior 12 weeks of Visit 1/Screening. 3. Subject has a history of hypersensitivity to a DPP-4 inhibitor. 4. Subject is currently participating, or has participated in a trial in which the subject received an investigational compound or used an investigational device within the prior 12 weeks of signing the ICF 5. Subject has a history of intolerance, hypersensitivity, or any other contraindication to metformin, glimepiride, or insulin glargine based upon the label in the country of the investigational site. 6. Subject is on a weight loss program and is not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery within 12 months prior to signing the informed consent. 7. Subject has undergone a surgical procedure within 4 weeks prior to signing informed consent or has planned major surgery during the trial. 8. Subject is on or likely to require treatment for ?14 consecutive days or repeated courses of pharmacologic doses of corticosteroids. 9. Subject is currently being treated for hyperthyroidism or subject is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks. 10. Subject is currently on or likely to require treatment with a prohibited medication 11. Subject is expecting to undergo hormonal therapy in preparation to donate eggs during the period of the trial, including 21 days following the last dose of blinded study medication. 12. Subject has a medical history of active liver disease (other than non-alcoholic hepatic steatosis) 13. Subject has HIV as assessed by medical history. 14. Subject has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months 15. Subject has poorly controlled hypertension defined as systolic blood pressure of ?160 mm Hg or diastolic blood pressure of ?90 mm Hg and blood pressure is unlikely to be within these limits by Visit 2/Week -2 with an adjustment in antihypertensive medication. 16. Subject has a history of malignancy ?5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer. 17. Subject has a clinically important hematological disorder 18. Subject has exclusionary laboratory values as listed in in the protocol. 19. Subject has a positive urine pregnancy test. 20. Subject is pregnant or breast-feeding, or is expecting to conceive during the trial, including 21 days following the last dose of blinded study medication. 21. Subject is, at the time of signing ICF a user of recreational or illicit drugs or has had a recent history of drug abuse. 22. Subject routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking. 23. Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that makes participation not in the subject's best interest. 24. Subject has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent, or intends to donate blood products within the projected duration of the trial OR subject has received, or is anticipated to receive, blood products within 12 weeks of signing informed consent or within the projected duration of the trial. 25. Subject is unlikely to adhere to the trial procedures, keep appointments, or is planning to relocate during the trial. 26. Subject has symptomatic hyperglycemia that, in the investigator's opinion, requires immediate initiation, adjustment, or addition of antihyperglycemic therapy or has a fasting plasma glucose consistently >260 mg/dL (14.4 mmol/L). 27 Subject has a clinically significant ECG abnormality which in the opinion of the investigator exposes the subject to risk by enrolling in the trial. 28. Subject has poorly controlled hypertension 29. Subject is on lipid-lowering medication or thyroid replacement therapy, and has not been on a stable therapy for the 4 weeks, or 6 weeks prior to Visit 3/Day 1. 29. 30 Subject has a positive urine pregnancy test (to be performed before randomization of the subject). 31. Subject has a site FFSG >250 mg/dL (13.8 mmol/L). 32. Subject has developed a new medical condition, suffered a change in status of an established medical condition, demonstrated a laboratory or ECG abnormality, or required a new treatment or medication during the pre-randomization period which meets any previously described trial exclusion criteria or which, in the opinion of the investigator, exposes the subject to risk by enrolling in the trial. |
1.Antecedentes de DMT1 o de cetoacidosis.El investigador considera que el sujeto posiblemente tiene una DMT1, confirmada por un péptido C<0,7 ng/mL (0,23 nmol/L). 2.Tratamiento con cualquier antihiperglucemiante distinto de la metformina exigida por el protocolo en las 12 semanas anteriores a la V1/selección. 3.Antecedentes de hipersensibilidad a un inhibidor de la DPP-4. 4.Participar o haber participado en otro ensayo en el que ha recibido un fármaco en investigación o ha utilizado un producto sanitario en investigación en las 12 semanas anteriores a la firma del consentimiento informado. 5.Antecedentes de intolerancia, hipersensibilidad o cualquier otra contraindicación a metformina, glimepirida o insulina glargina, según la ficha técnica del país del centro de investigación. 6.El sujeto participa en un programa de pérdida de peso y no se encuentra en la fase de mantenimiento o ha iniciado un medicamento para perder peso o ha sido sometido a cirugía bariátrica en los 12 meses anteriores a la firma del consentimiento informado. 7.Haberse sometido a un procedimiento quirúrgico en las 4 semanas anteriores a la firma del consentimiento informado o tener programada una intervención quirúrgica mayor durante el ensayo. 8.El sujeto recibe o es probable que precise tratamiento durante >/=14 días consecutivos o ciclos repetidos de corticosteroides en dosis farmacológicas. 9.Recibir tratamiento por hipertiroidismo o tratamiento tiroideo sustitutivo y no haber logrado mantenerse con una dosis estable durante como mínimo 6 semanas. 10.El sujeto recibe o es probable que precise tratamiento con un medicamento prohibido. 11.Tener previsto someterse a un tratamiento hormonal para la donación de óvulos durante el periodo del ensayo, incluidos los 21 días siguientes a la última dosis de la medicación enmascarada del estudio. 12.Antecedentes de hepatopatía activa(distinta de la esteatosis hepática no alcohólica). 13.Portador del VIH, según su historia clínica. 14.Signos o síntomas nuevos o en deterioro de cardiopatía coronaria o de insuficiencia cardiaca congestiva en los 3 últimos meses. 15.Hipertensión mal controlada, que se define como una presión arterial sistólica >/=160 mm Hg o una diastólica >/=90 mm Hg, y no es probable que su presión arterial se encuentre debajo de estos límites en la V2/semana -2 con un ajuste de su medicación antihipertensora. 16.Antecedentes de neoplasia maligna </=5 años antes de la firma del consentimiento informado, con excepción del carcinoma cutáneo basocelular o espinocelular o el cáncer de cuello uterino in situ. 17.Trastorno hematológico clínicamente importante. 18.Presentar unos valores de laboratorio que son motivo de exclusión de acuerdo al protocolo. 19.Prueba de embarazo en orina positiva. 20.Estar embarazada o en periodo en lactancia o tener intención de concebir durante el ensayo, incluidos los 21 días siguientes a la última dosis de la medicación enmascarada del estudio. 21.Consumir o utilizar drogas con fines recreativos en el momento de la firma del consentimiento informado, o tener antecedentes recientes de drogadicción. 22.Consumir habitualmente >2 bebidas alcohólicas al día o >14 a la semana, o tener intoxicaciones etílicas agudas. 23.Antecedentes o presencia actual de cualquier trastorno, tratamiento, anomalía de laboratorio u otra circunstancia que hace que su participación no sea lo mejor para el sujeto. 24.El sujeto ha donado hemoderivados o ha sido sometido a una flebotomía >300 mL en las 8 semanas previas a la firma del consentimiento informado, o tiene intención de donar hemoderivados dentro de la duración prevista del ensayo O ha recibido o está previsto que reciba hemoderivados en las 12 semanas siguientes a la firma del consentimiento informado o dentro de la duración prevista del ensayo. 25.Sujeto que no es probable que cumpla los procedimientos del ensayo o acuda a las citas, o que tenga previsto cambiar de domicilio durante el ensayo. 26.Hiperglucemia sintomática que, precisa de inmediato el inicio, el ajuste o la adición de tratamiento antihiperglucemiante o presentar una glucosa plasmática en ayunas uniformemente >260 mg/dL (14,4 mmol/L). 27.Anomalía electrocardiográfica clínicamente importante que, le podría suponer un riesgo si participara en el ensayo. 28.Hipertensión mal controlada. 29.Recibir medicación hipolipemiante o tratamiento tiroideo sustitutivo y no haber mantenido una pauta estable durante las 4 semanas, o 6 semanas anteriores a la visita 3/día 1. 30.Prueba de embarazo en orina positiva(se realizará antes de la aleatorización de la sujeto) 31.Presentar una GSCA>250 mg/dL(13,8 mmol/L). 32.Trastorno médico nuevo, cambio en el estado de un trastorno médico establecido, anomalía de laboratorio o del ECG o requerir un nuevo tratamiento o una nueva medicación durante el periodo de prealeatorización que cumpla cualquiera de los criterios de exclusión del ensayo o que podría suponer un riesgo si participara en el ensayo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in A1C at Week 24. |
Cambio respecto al valor basal de la A1C en la semana 24. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Change from baseline in 2-hour PMG at Week 24; - Change from baseline in FPG at Week 24. - Change from baseline in A1C at Week 104; - Change from baseline in FPG at Week 104; - Proportion of subjects attaining A1C glycemic goals of <7% and <6.5% after 24 and 104 weeks of treatment; - Change from baseline in post-meal glucose total AUC at Week 24; - Change from baseline in fasting insulin at Week 24 and Week 104; - Time to rescue over 24 and 104 weeks; - Proportion of subjects requiring rescue therapy at Week 24 and 104. - Safety Endpoints |
-Cambio respecto al valor basal de la GPP tras 2 horas en la semana 24. -Cambio respecto al valor basal de la GPA en la semana 24. -Cambio respecto al valor basal de la A1C en la semana 104. -Cambio respecto al valor basal de la GPA en la semana 104. -Porcentaje de sujetos que alcancen unos objetivos glucémicos de A1C de <7 % y <6,5 % después de 24 y 104 semanas de tratamiento. -Cambio respecto al valor basal del AUC total de la glucosa posprandial en la semana 24. -Cambios respecto al valor basal de la insulina en ayunas en la semana 24 y en la semana 104. -Tiempo hasta el tratamiento de rescate a lo largo de 24 y 104 semanas. -Porcentaje de sujetos que requieran tratamiento de rescate en las semanas 24 y 104. -Criterios de valoración de la seguridad |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 24 and 104 |
Semanas 24 y 104 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
European Union |
Brazil |
India |
Mexico |
Peru |
Russian Federation |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS |
Última visita último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |