| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type 2 Diabetes Mellitus (T2DM) |
| diabetes mellitus de tipo 2 (DMT2) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Type 2 Diabetes Mellitus (T2DM) |
| diabetes mellitus de tipo 2 (DMT2) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| 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 |
| In subjects with T2DM with inadequate glycemic control on metformin and sitagliptin, who initiate and titrate insulin glargine (LANTUS®), to assess the effect of continuing sitagliptin relative to withdrawing sitagliptin on: (1) HbA1c (A1C) after 30 weeks; (2) the event rate of documented symptomatic hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L) over 30 weeks; (3) general safety and tolerability over 30 weeks. |
| En sujetos con DMT2 y control insuficiente de la glucemia con metformina y sitagliptina, en los que inicie la administración de insulina glargina (LANTUS®) y se ajuste su dosis, evaluar el efecto de la continuación con sitagliptina en comparación con su retirada sobre: (1) HbA1c después de 30 semanas; (2) tasa de episodios de hipoglucemia sintomática documentada con una glucemia ? 70 mg/dl (? 3,9 mmol/l) durante 30 semanas; (3) seguridad y tolerabilidad generales durante 30 semanas |
|
| E.2.2 | Secondary objectives of the trial |
| In subjects with T2DM with inadequate glycemic control on metformin and sit agliptin, who initiate and titrate insulin glargine (LANTUS®), to assess the effect of continuing sitagliptin relative to withdrawing sitagliptin on:1) the incidence of documented symptomatic hypoglycemia with blood glucose ?70 mg/dL over 30 weeks.2) the event rate of documented symptomatic hypoglycemia with blood glucose <56 mg/dL over 30 weeks.3) the incidence of documented hypoglycemia with blood glucose ?70 mg/dL over 30 weeks.4 the incidence of documented symptomatic hypoglycemia with bloodglucose <56 mg/dL over 30 weeks.5) the daily dose of insulin after 30 weeks.6) the event rate of documented hypoglycemia with blood glucose ?70 mg/dL over 30 weeks.7) the event rate of documented hypoglycemia with blood glucose <56 mg/dL over 30 weeks. |
| En sujetos con DMT2 y control insuficiente de la glucemia con metformina y sitagliptina, en los que inicie la administración de insulina glargina (LANTUS®) y se ajuste su dosis, evaluar el efecto de la continuación con sitagliptina en comparación con su retirada sobre: 1) incidencia de episodios de hipoglucemia sintomática documentada con unaglucemia ? 70 mg/dl durante 30 semanas.2) tasa de episodios de hipoglucemia sintomática documentada con una glucemia < 56 mg/dl durante 30 semanas. 3) incidencia de episodios de hipoglucemia documentada con una glucemia ? 70 mg/dl durante 30 semanas.4) incidencia de episodios de hipoglucemia sintomática documentada con una glucemia < 56 mg/dl durante 30 semanas. 5) dosis diaria de insulina al cabo de 30 semanas.6) tasa de episodios de hipoglucemia documentada con una glucemia ? 70 mg/dl durante 30 semanas.7) tasa de episodios de hipoglucemia documentada con una glucemia< 56 mg/dl durante 30 semanas. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The
objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is
to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time. |
Merck realizará investigaciones biomédicas futuras con las muestras obtenidas para tal finalidad durante este ensayo clínico. Estas investigaciones tendrán por objeto el análisis de biomarcadores con el fin de abordar aspectos nuevos que no se describen en otras partes del
protocolo (como parte del ensayo principal) y solo se llevarán a cabo en muestras de los pacientes que hayan otorgado el consentimiento correspondiente. El objetivo de la obtención de muestras para investigaciones biomédicas futuras es estudiar e identificar
biomarcadores que proporcionen información a los científicos sobre las enfermedades y sus tratamientos. El objetivo último es utilizar tal información para desarrollar fármacos más seguros y eficaces o para garantizar que los sujetos reciban la dosis correcta del fármaco en el
momento preciso. |
|
| E.3 | Principal inclusion criteria |
| In order to be eligible for participation in this trial, the subject must: (1) have T2DM and be > or = 18 years of age on the day of signing ICF; (2) be on one of the following treatment regimens: (a) stable dose of sitagliptin (100 mg/day) and metformin IR or XR (> or = 1500 mg/day) either co-administered or as a FDC for > or = 12 weeks with A1C between 7.5% and 11.0%, inclusive; (b) stable dose of metformin IR or XR (> or = 1500 mg/day) and another DPP-4 inhibitor (at maximum labeled dose), other than sitagliptin, either co-administered or as a FDC, for > or = 12 weeks with A1C between 7.5% and 11.0%, inclusive; (c) stable dose of sitagliptin (100 mg/day) and metformin IR or XR (> or = 1500 mg/day) either co-administered or as a FDC, and a sulfonylurea for > or = 12 weeks OR stable dose of metformin IR or XR (> or = 1500 mg/day) and a sulfonylurea administered as a FDC and sitagliptin (100 mg/day) with A1C between 7.0% and 10.0%, inclusive; (d) stable dose of metformin IR or XR (> or = 1500 mg/day) and another DPP-4 inhibitor (at maximum labeled dose), other than sitagliptin, either co-administered or as a FDC, and a sulfonylurea for > or = 12 weeks OR stable dose of metformin IR or XR (> or = 1500 mg/day) and a sulfonylurea administered as a FDC and another DPP-4 inhibitor other than sitagliptin with A1C between 7.0% and 10.0%, inclusive; (e) stable dose of metformin IR or XR (> or = 1500 mg/day) and a sulfonylurea either co-administered or as a FDC for > or = 12 weeks with A1C between 7.5% and 11.0% (> or = 58 mmol/mol and < or = 97 mmol/mol), inclusive. (3) At Visit 3 A1C of 7.5% to 11.0% (?58 mmol/mol and ? 97 mmol/mol). |
| Para poder participar en este ensayo, un sujeto deberá: 1. Presentar DMT2 y tener 18 añoso más el día de firma del consentimiento informado. 2. Estar recibiendo una de las siguientes pautas de tratamiento: Dosis estable de sitagliptina (100 mg/día) y metformina LI o LP (? 1500 mg/día) administradas conjuntamente o como CDF durante ? 12 semanas con una HbA1c de entre el 7,5% y 11,0% ambos inclusive. O ( b)Dosis estable de metformina LI o LP (? 1500 mg/día) y otro inhibidor de la DPP-4 (en la dosis máxima autorizada), distinto de itagliptina, administrados conjuntamente o como CDF, durante ? 12 semanas con una HbA1c de entre el 7,5% y 11,0%, ambos inclusive. O (c) Dosis estable de sitagliptina (100 mg/día) y metformina LI o LP (? 1500 mg/día) administradas conjuntamente o como CDF y una sulfonilurea durante ? 12 semanas O dosis estable de metformina LI o LP (? 1500 mg/día) y una sulfonilurea administradas como CDF y sitagliptina (100 mg/día) con una HbA1c de entre el 7,0% y 10,0%, ambos inclusive. (d) Dosis estable de metformina LI o LP (? 1500 mg/día) y otro inhibidor de la DPP-4 (en la dosis máxima autorizada), distinto de sitagliptina, administrados conjuntamente o como CDF y una sulfonilurea durante ?12 semanas O dosis estable de metformina LI o LP (? 1500 mg/día) y una sulfonilurea administradas como CDF y otro inhibidor de la DPP-4, distinto de sitagliptina, con una HbA1c de entre el 7,0% y 10,0%, ambos inclusive. O (e) Dosis estable de metformina LI o LP (? 1500 mg/día) y una sulfonilurea administradas conjuntamente o como CDF durante ? 12 semanas con una HbA1c de entre el 7,5% y 11,0% (? 58 y ? 97 mmol/mol), ambos inclusive. 3. HbA1c de entre el 7,5% y 11,0% (? 58 y ? 97 mmol/mol). |
|
| E.4 | Principal exclusion criteria |
| The subject must be excluded from participating in the trial if the subject: (1) has been treated with any AHA other than protocol-specified agents (i.e., other than metformin, DPP-4 inhibitor, or sulfonylurea agent) within the prior 12 weeks; (2) has a history of 2 or more episodes of hypoglycemia resulting in seizure, coma, or loss of consciousness, OR subject has had recurrent (> or = 3 times per week) episodes of hypoglycemia over the past 8 weeks; (3) has a history of type 1 diabetes mellitus (T1DM) or ketoacidosis, or has a history of latent autoimmune diabetes of adults (LADA), or subject is assessed by the investigator as possibly having T1DM or LADA confirmed with a C-peptide <0.7 ng/mL (<0.23 nmol/L), or has a history of other specific types of diabetes; (4) has a history of intolerance or hypersensitivity to sitagliptin, insulin, or metformin or any contraindication to sitagliptin, insulin, or metformin based upon the label of the country of the investigational site; (5) is currently participating, or has participated, in a study in which the subject received an investigational compound or used an investigational device within the prior 12 weeks of signing informed consent or is not willing to refrain from participating in another study; (6) is currently on or likely to require treatment with a prohibited medication (see Section 5.5.2 of protocol). Example: is on, or likely to require treatment with more than 14 consecutive days or repeated courses of pharmacologic doses of corticosteroids; (8) is pregnant or breast-feeding; (9) has an exclusionary laboratory value as listed in the protocol; (10) At Visit 4, has a site fasting fingerstick glucose of <130 mg/dL (7.2 mmol/L) or >270 mg/dL (15.0 mmol/L). |
| No podrán participar en el ensayo los sujetos que: (1) Hayan recibido tratamiento con cualquier antidiabético distinto de los especificadosen el protocolo (es decir, distinto de metformina, inhibidor de la DPP-4 osulfonilurea) en las 12 semanas precedentes. (2) Tengan antecedentes de dos o más episodios de hipoglucemia que hayan acabado en crisis convulsiva, coma o pérdida del conocimiento O hayan sufrido episodios recurrentes (? 3 veces por semana) de hipoglucemia durante las 8 últimas semanas. (3) Tengan antecedentes de diabetes mellitus de tipo (DMT1), cetoacidosis o diabetes autoinmunitaria latente del adulto (DALA), tengan posiblemente, según la evaluación del investigador, DMT1 o DALA confirmada mediante una determinación de péptido C < 0,7 ng/ml (< 0,23 nmol/l) o tengan antecedentes de otros tipos específicos de diabetes. (4) Tengan antecedentes de intolerancia o hipersensibilidad a la sitagliptina o insulina o tengan alguna contraindicación para el uso de sitagliptina o insulina, de conformidad con la ficha técnica vigente en el país del centro de investigación. (5) Estén participando, o lo hayan hecho ya, en un estudio en el que hayan recibido un fármaco en investigación o hayan utilizado un dispositivo en investigación en las 12 semanas previas a la firma del consentimiento informado o no estén dispuesto a abstenerse de participar en ningún otro estudio. (6) Estén recibiendo o es probable que requieran tratamiento con un medicamento prohibido (en la sección 3.2.1.2 se recoge una lista de los medicamentos prohibidos).Por ejemplo, el sujeto está recibiendo o es probable que precise tratamiento con dosis farmacológicas de corticoides durante 14 días consecutivos o en ciclos repetidos. (8) Estén embarazadas o en período de lactancia.(9) Tengan un valor analítico que sea motivo de exclusión listados en el protocolo. (10) En la visita 4 ,tengan una glucemia capilar en ayunas medida en el centro < 130 mg/dl (7,2 mmol/l) o > 270 mg/dl (15,0 mmol/l). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
(1) Change from baseline in A1C at Week 30;
(2) Event rate of documented symptomatic hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L) over 30 weeks. |
1) Variación con respecto al valor inicial de la HbA1c en la semana 30.
(2) Tasa de episodios de hipoglucemia sintomática documentada con una glucemia ? 70 mg/dl (? 3,9 mmol/l) durante 30 semanas |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1) Event rate of documented symptomatic hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L) over 30 weeks;
(2) Incidence of each of the following over 30 weeks:
(a) documented symptomatic hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L);
(b) documented hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L);
(c) documented symptomatic hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L);
(d) documented hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L);
(3) Change from baseline in total daily insulin dose at Week 30;
(4) Event rate of each of the following over 30 weeks:
(a) documented hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L);
(b) documented hypoglycemia with blood glucose <56 mg/dL (< or = 3.1 mmol/L);
(5) Proportion of subjects at A1C goal <7.0% (<53 mmol/mol) at Week 30;
(6) Proportion of subjects at A1C goal <7.0% (<53 mmol/mol) at Week 30 with no documented hypoglycemia with blood glucose < or = 70 mg/dL (< or = 3.9 mmol/L);
(7) Change from baseline in FPG at Week 30. |
(1) Tasa de episodios de hipoglucemia sintomática documentada con una glucemia < 56 mg/dl (? 3,1 mmol/l) durante 30 semanas.
(2) Incidencia de cada un de los siguientes durante 30 semanas
(a) episodios de hipoglucemia sintomática documentada con una glucemia ? 70 mg/dl (? 3,9 mmol/l)
(b) episodios de hipoglucemia documentada con una glucemia ? 70 mg/dl (? 3,9 mmol/l)
(C) episodios de hipoglucemia sintomática documentada con una glucemia < 56 mg/dl (? 3,1 mmol/l)
(d) episodios de hipoglucemia documentada con una glucemia< 56 mg/dl (? 3,1 mmol/l)
(3) Cambio del valor inicial en la dosis total diaria de insulina al cabo de la semana 30
(4) Tasa de episodios de cada uno de los siguientes durante 30 semanas
(a) episodios de hipoglucemia documentada con una glucemia ? 70 mg/dl (? 3,9 mmol/l)
(b) episodios de hipoglucemia documentada con una glucemia< 56 mg/dl (? 3,1 mmol/l)
(5) proporción de sujetos con una HbA1c < 7,0% (< 53 mmol/mol) al cabo de 30 semanas.
(6) proporción de sujetos con una HbA1c < 7,0% (< 53 mmol/mol) al cabo de 30 semanas sin episodios de hipoglucemia documentada con una glucemia ? 70 mg/dl (? 3,9 mmol/l).
(7) Cambio del valor inicial en la glucemia en ayunas (GA) al cabo de 30 semanas. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | Yes |
| 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) | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 53 |
| 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 |
| Australia |
| Canada |
| Czech Republic |
| Denmark |
| Estonia |
| France |
| Germany |
| Hungary |
| Israel |
| Korea, Republic of |
| Latvia |
| Philippines |
| Poland |
| Puerto Rico |
| Romania |
| Russian Federation |
| Spain |
| Turkey |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 |
| último paciente última visita |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 20 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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