| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type 1 Diabetes Mellitus |
| diabetes mellitus de tipo 1 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Diabetes Mellitus |
| diabetes mellitus |
|
| 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 | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067584 |
| E.1.2 | Term | Type 1 diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 |
1. To assess the effect of treatment with MK-1293 compared with
Lantus? on anti-insulin antibody development after 24 weeks of treatment.
2. To assess the non-inferiority of treatment with MK-1293 compared with Lantus? on A1C after 24 weeks of treatment. |
1.valorar el efecto del tratamiento con MK-1293 en comparación con Lantus? en el desarrollo de anticuerpos antiinsulina después de 24 semanas de tratamiento.
2.evaluar la no inferioridad del tratamiento con MK-1293 en comparación con Lantus? en la A1C después de 24 semanas de tratamiento. |
|
| E.2.2 | Secondary objectives of the trial |
1. To assess the equivalence of treatment with MK-1293 compared with Lantus? on A1C after 24 weeks of treatment.
2. To assess the effect of treatment with MK-1293 compared with
Lantus? on anti-insulin antibody development after 52 weeks of treatment.
3. To assess the effect of treatment with MK-1293 compared with
Lantus? on A1C after 52 weeks of treatment.
4. To assess the safety and tolerability, including body weight, hypoglycemia and adverse events, of MK-1293 compared to Lantus? after 24 and 52 weeks of treatment.
5. To assess the effect of treatment with MK-1293 compared with
Lantus? on insulin dose (units) (total and by component [basal and bolus]) and insulin dose per body weight unit (unit/kg) (total and by component [basal and bolus]) after 24 and 52 weeks of treatment.
6. To assess the effect of treatment with MK-1293 compared with
Lantus? on fasting plasma glucose and 7-point self-monitored blood glucose (SMBG) profiles after 24 and 52 weeks of treatment. |
1.evaluar la equivalencia del tratamiento con MK-1293 en comparación con Lantus? en la A1C después de 24 semanas de tratamiento
2.valorar el efecto del tratamiento con MK-1293 en comparación con Lantus? en el desarrollo de anticuerpos antiinsulina después de 52 semanas de tratamiento.
3.valorar el efecto del tratamiento con MK-1293 en comparación con Lantus? en la A1C después de 52 semanas de tratamiento
4.valorar la seguridad y tolerabilidad, incluso el peso corporal, la hipoglucemia y los acontecimientos adversos, de MK-1293 en comparación con Lantus? después de 24 y 52 semanas de tratamiento.
5.valorar el efecto del tratamiento con MK-1293 en comparación con Lantus? sobre la dosis de insulina (unidades) (total y por componente [basal y en bolo]) y la dosis de insulina por unidad de peso corporal (unidad/kg) (total y por componente [basal y en bolo]) después de 24 y 52 semanas de tratamiento |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject has had T1DM for at least one year prior to Visit 1 and has a Visit 1 C-peptide ?0.7 ng/mL (0.23 nmol/L) when plasma glucose is >90 mg/dL (5 mmol/L).
2. Subject currently on a regimen of basal insulin and has been using rDNA origin prandial insulin (i.e. lispro, aspart, glulisine) for a total duration of ?4 weeks.
3. Subject is ?18 years of age on day of signing informed consent.
4. Subject has a Visit 1/Screening A1C of ?11.0%.
5. Subject has a body mass index (BMI) <45 kg/m2.
6. Subject is a male, or a female who is highly unlikely to conceive as indicated by meeting at least one of the following criteria:
-Subject is not of reproductive potential. A female subject who is not of
reproductive potential is defined as one who has either (1) 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 (2) had bilateral oophorectomy and/or hysterectomy, or had bilateral tubal ligation at least 6 weeks prior to screening.
-Subject is of reproductive potential and agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control within the projected duration of the study and for 14 days after the last dose of study medication. Acceptable methods of birth control are: hormonal contraception, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy.
7. Subject understands the study procedures; alternative treatments available, risks involved with the study, and voluntarily agree 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.
8. Subject demonstrates compliance with eDiary use as shown by uploading fingerstick glucose values from the study supplied glucose meter daily. |
1.El sujeto ha padecido T1DM durante al menos un año antes de la Visita 1 y en la Visita 1 registra valores de péptido C ?0,7 ng/ml (0,23 nmol/l) cuando la glucosa en sangre es de >90 mg/dl (5 mmol/l).
2.El sujeto lleva recibiendo tratamiento con insulina prandial procedente del ADNr (es decir, lispro, aspart, glulisina) durante ?4 semanas y sigue recibiéndolo
3.El sujeto tiene ? 18 años de edad el día en que firma el consentimiento informado
4.La A1C del sujeto en la Visita 1/Selección es de ? 11,0%.
5.El sujeto tiene un índice de masa corporal (IMC) < 45 kg/m2
6.El sujeto es hombre o mujer con pocas probabilidades de concebir un hijo, ya que cumple con al menos uno de los siguientes criterios:El potencial reproductivo del sujeto es nulo.El sujeto tiene potencial reproductivo y acepta practicar la abstinencia o utilizar (o su pareja) un método anticonceptivo aceptable durante el período previsto del estudio y hasta que transcurran 14 días desde la última dosis de la medicación del estudio.
7.El sujeto entiende los procedimientos del estudio, los tratamientos alternativos disponibles y los riesgos que implica el estudio, y acepta voluntariamente participar a través de un consentimiento informado escrito.
8El sujeto demuestra que ha completado el diario electrónico cargando diariamente los valores de glucosa obtenidos mediante punción capilar con el medidor de glucosa suministrado del estudio. |
|
| E.4 | Principal exclusion criteria |
1. Subject has had one or more severe hypoglycemic episodes associated with hypoglycemic seizure or loss of consciousness within the past 6 months.
2. Subject has a history of ketoacidosis in the last 6 months.
3. Subject, as assessed by the investigator, is not appropriate for or does not agree to target a fasting glucose of 70-100 mg/dL [3.9 -5.6 mmol/L].
4. Subject has a history of intolerance or hypersensitivity to Lantus? or
contraindication to Lantus? or one of its excipients based on the label of the country of the investigational site.
5. Subject has used a formulation of insulin glargine other than Lantus?.
6. Subject received injectable incretin-based therapy (e.g., Victoza?, Byetta?) within the prior 8 weeks.
7. Subject is on a weight loss program and not in the maintenance phase, or has started a weight loss medication (such as orlistat) within the prior 8 weeks.
8. Subject has undergone bariatric surgery within 12 months prior to signing the informed consent.
9. Subject is currently participating in, or has participated in a study with an investigational compound or device within the prior 12 weeks of signing informed consent or is not willing to refrain from participating in another study.
10. Subject is likely to require treatment for ?2 consecutive weeks or repeated courses of pharmacologic doses of corticosteroids.
11. Subject has undergone a surgical procedure within 4 weeks prior to signing informed consent or has planned major surgery during the study.
12. Subject has new or worsening signs or symptoms of coronary heart disease or congestive heart failure (NYHA Class II - IV cardiac status)
within the past 3 months, or has any of the following disorders within the past 3 months: Acute coronary syndrome (e.g., MI or unstable angina), Coronary artery intervention (e.g., CABG or PTCA), Stroke or transient ischemic neurological disorder.
13. Subject has severe peripheral vascular disease (e.g., claudication with minimal activity, a non-healing ischemic ulcer, or disease which is likely to require surgery or angioplasty).
14. Subject has a systolic blood pressure ?160 mm Hg or a diastolic ?95 mm Hg and blood pressure is not considered likely to be under these limits at Visit 2/Day 1 with an adjustment in antihypertensive medication.
15. Subject has chronic myopathy, or a progressive neurological or neuromuscular disorder (e.g., multiple sclerosis or polymyositis).
16. Subject has active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).
17. Subject has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or symptomatic gallbladder disease.
18. Subject has human immunodeficiency virus (HIV) as assessed by medical history.
19. Subject has a clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia).
20. 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.
21. Subject has a history of melanoma, leukemia, lymphoma, or renal cell carcinoma.
22. Subject is currently being treated for hyperthyroidism.
23. Subject has been on stable dose of thyroid hormone replacement therapy for <6 weeks.
24. Subject is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
25. Subject is pregnant or breast-feeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug.
26. 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 study.
27. Subject has poor mental function or any other reason to expect that the subject may have difficulty in complying with the requirements of the study, such as Self- Monitoring Blood Glucose (SMBG), being available for telephone calls from the investigational site to discuss insulin titration, adhering to the study procedures, keeping study appointments, or planning to relocate during the study.
28. Subject is a night shift worker. This causes difficulty complying with the overnight fast requirement and has potential for confounding the 7-point SMBG analysis.
29. Subject has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that: makes participation not in the subject's best interest, might interfere with the subject?s participation for the full duration of the study, might confound the results of the study.
30. Subject has a clinically significant ECG abnormality which in the opinion of the investigator exposes the subject to risk by enrolling in the study. |
1.El sujeto ha sufrido uno o más episodios hipoglucémicos graves asociados con crisis convulsivas o pérdidas de conciencia hipoglucémicas en los últimos 6 meses.
2.El sujeto tiene un historial de cetoacidosis en los últimos 6 meses.
3.El investigador ha determinado que el sujeto no es apto para el objetivo de glucosa en ayunas de 70-100 mg/dL [3,9 - 5,6 mml/l] o no se compromete a alcanzar este objetivo.
4.El sujeto tiene un historial de intolerancia o hipersensibilidad a Lantus? o alguno de sus excipientes, o bien el uso de Lantus? (o alguno de sus excipientes) está contraindicado en su caso, según la etiqueta del país del centro de investigación
5.El sujeto ha utilizado una formulación de insulina glargina distinta de Lantus?.
6.El sujeto se sometió a una terapia de incretina (p. ej., Victoza?, Byetta?) en las 8 semanas anteriores.
7.El sujeto está siguiendo un programa de adelgazamiento y no se encuentra en la fase de mantenimiento, o ha empezado a tomar un medicamento para adelgazar (como orlistat) en las 8 semanas anteriores.
8.El sujeto se ha sometido a un procedimiento de cirugía bariátrica en los 12 meses anteriores a la firma del consentimiento informado
9.El sujeto está participando actualmente en un estudio con un compuesto o dispositivo experimental, o lo ha hecho en las 12 semanas anteriores a la firma del consentimiento informado y no está dispuesto a abstenerse de participar en otro estudio.
10.Es probable que el sujeto requiera tratamiento durante ? 2 semanas consecutivas o dosis farmacológicas repetidas de corticoesteroides.
11.El sujeto se ha sometido a un procedimiento quirúrgico en las 4 semanas anteriores a la firma del consentimiento informado o deberá someterse a cirugía mayor durante el estudio.
12.El sujeto ha presentado nuevos síntomas o un empeoramiento de los síntomas de enfermedad coronaria o insuficiencia cardiaca congestiva (estado cardiaco de Clase II-IV de la NYHA [consulte el Apéndice 6.5]) en los últimos 3 meses, o ha sufrido cualquiera de los siguientes trastornos en los últimos 3 meses: Síndrome coronario agudo (p. ej., IM o angina inestable),Intervención arterial coronaria (p. ej., CABG o PTCA), Accidente cerebrovascular o trastorno neurológico isquémico transitorio
13.El sujeto sufre una enfermedad vascular periférica grave (p. ej., claudicación con mínima actividad, úlcera isquémica que no cicatriza o enfermedad que probablemente requiera cirugía o angioplastia).
14.El sujeto tiene una presión arterial sistólica ? 160 mm Hg o una presión arterial diastólica ? 95 mm Hg y no es probable que se encuentre por debajo de esos límites en la Visita 2/Día 1 tras un ajuste del medicamento antihipertensivo.
15.El sujeto sufre miopatía crónica o un trastorno neurológico o neuromuscular progresivo (p. ej., esclerosis múltiple o polimiositis).
16.El sujeto tiene nefropatía activa (es decir, síndrome nefrótico o glomerulonefritis).
17.El sujeto tiene un historial clínico de enfermedad hepática activa (diferente a la esteatosis hepática no alcohólica), inclusive hepatitis B o C activa crónica (según el historial clínico), cirrosis biliar primaria o enfermedad de la vesícula biliar sintomática.
18.El sujeto es portador del virus de inmunodeficiencia humana (VIH), según el historial clínico.
19.El sujeto sufre un trastorno hematológico importante desde un punto de vista clínico (como anemia aplásica, síndrome mieloproliferativo o mielodisplásico, o trombocitopenia).
20.El sujeto tiene un historial de neoplasia maligna en los 5 años anteriores a la firma del consentimiento informado, salvo cáncer de piel de células basales o de células escamosas, o cáncer de cuello uterino in situ adecuadamente tratado
21.El sujeto tiene un historial de melanoma, leucemia, linfoma o carcinoma de células renales.
22.El sujeto está recibiendo actualmente tratamiento para el hipertiroidismo
23.El sujeto lleva < 6 semanas tomando una dosis estable de terapia de sustitución de la hormona tiroidea
24.En el momento de firmar el consentimiento informado, el sujeto consume drogas ilícitas o recreativas, o tiene un historial reciente (durante el último año) alcoholismo o drogadicción.
25.La participante está embarazada o amamantando, o planea quedar embarazada o donar óvulos durante el estudio, en incluso los 14 días posteriores a la última dosis del fármaco del estudio.
26.El sujeto ha donado productos sanguíneos o se ha sometido a una flebotomía de > 300 ml en el plazo de 8 semanas tras firmar el consentimiento informado, o planea donar hemoderivados durante el tiempo estimado del estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
-Change from baseline in A1C at Week 24
-Proportions of subjects with any confirmed positive Anti-Insulin Antibody (AIA) (including baseline) up through Week 24.
-Proportion of subjects who have negative AIA at baseline but develop confirmed positive AIA at any time up through Week 24.
-Changes from baseline in AIA titers after 24 weeks of treatment.
-Proportion of subjects with any insulin neutralizing antibodies (based on the subjects who have confirmed positive AIA at the corresponding time point) up through 24 weeks of treatment (including baseline) |
Cambio del valor inicial de A1C en la Semana 24
La proporción de sujetos con cualquier valor confirmado de anticuerpos antiinsulina (AIA) (incluso en el momento inicial) hasta la Semana 24.
Proporción de sujetos que presentan resultados negativos de AIA al inicio del estudio, pero resultados positivos confirmados en cualquier momento hasta la Semana 24.
Cambios de AIA desde el momento inicial tras 24 semanas de tratamiento.
Proporción de sujetos con anticuerpos neutralizadores de la insulina (en base a sujetos que tienen resultados positivos confirmados de AIA en el momento correspondiente) hasta las 24 semanas de tratamiento (incluido el momento inicial). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
-Change from baseline in A1C at Week 52
-Insulin dose (total and by component [basal and bolus]) at Week 24 and Week 52
-Insulin dose per kg of body weight (unit/kg) (total and by component [basal and bolus]) at Week 24 and Week 52
-Change from baseline in fasting plasma glucose (FPG) at Week 24 and Week 52
-Change from baseline in 7-point SMBG (7-point average) at Week 24 and Week 52
-Proportion of subjects attaining A1C glycemic goals of <7% and <6.5% after 24 and 52 weeks of treatment |
Cambio del valor inicial de A1C en la Semana 52
Dosis de insulina (total y por componente [basal y en bolo]) en la Semana 24 y la Semana 52
Dosis de insulina por kg de peso corporal (unidad / kg) (total y por componente [basal y en bolo]) en la Semana 24 y la Semana 52
Cambio del valor inicial de glucosa en plasma en ayunas (FPG) en la Semana 24 y en la Semana 52
Cambio del valor inicial de SMBG en 7 puntos (promedio de 7 puntos) en las Semanas 24 y 52
Proporción de sujetos que alcanzan los objetivos glucémicos de A1C de < 7% y < 6,5% tras 24 y 52 semanas de tratamiento |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 24 and week 52 |
| Semana 24 y Semana 52 |
|
| 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 | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | No |
| 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 |
| New Zealand |
| Australia |
| Colombia |
| Mexico |
| Peru |
| South Africa |
| 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 |
| LA ULTIMA VISITA DEL ULTIMO PACIENTE ( UVUP) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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