| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Type 1 Diabetes Mellitus |
| Diabete Mellito di tipo I |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 14.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10027433 |
| E.1.2 | Term | Metabolism and nutrition disorders |
| 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 |
| The primary objective of this study is to demonstrate that glycemic control as measured by HbA1c at 26 weeks for LY2605541 is non-inferior to insulin glargine when each is combined with pre-prandial insulin lispro in patients with type 1 diabetes mellitus. |
| L'obiettivo primario è quello di dimostrare che il controllo glicemico, secondo quanto misurato dall'emoglobina A1c (HbA1c) a 26 settimane per LY2605541 non è inferiore a quello dell'insulina glargine se ciascuna è combinata con l'insulina lispro pre-prandiale in pazienti affetti da diabete mellito di tipo 1 (T1DM). |
|
| E.2.2 | Secondary objectives of the trial |
| Gated:To demonstrate that LY2605541 is superior to insulin glargine (both in combination with pre-prandial insulin lispro) at 26 weeks for: 1.Nocturnal hypoglycemia rate.2.HbA1c 3.Proportion of patients with HbA1c <7.0% 4.FSG by laboratory measurement 5.Total hypoglycemia rate. Non-gated: To compare the efficacy and safety of LY2605541 versus insulin glargine (both in combination with pre-prandial insulin lispro) treatment groups for:1.Total and nocturnal hypoglycemia rates and incidences 2.Weight change from baseline 3.SMBG 9-point profiles 4.Proportion of patients with HbA1c <7.0% and ≤6.5% 5.Proportion of patients with HbA1c <7.0% without nocturnal hypoglycemia 7.HbA1c change from baseline 8.HbA1c at 52 and 78 weeks 9.Basal, mealtime, and total insulin dose (units and units/kg) 10.Triglycerides, total cholesterol, LDL-cholesterol,HDL-cholesterol |
| Gli obiettivi secondari dello studio sono i seguenti: Controllati:Dimostrare che LY2605541 è superiore all'insulina glargine (anche in combinazione con l'insulina lispro pre-prandiale) per quanto segue:1.Tasso di ipoglicemia notturna 2.HbA1c 3.Proporzione di pazienti con HbA1c < 7,0% dopo 26 settimane 4.Glicemia a digiuno (FSG) mediante misurazioni di laboratorio per LY2605541 5.Tasso di ipoglicemia totale.Non controllati: Comparare l'efficacia e la sicurezza di LY2605541 rispetto ai gruppi di trattamento con insulina glargine (entrambe in combinazione con insulina lispro preprandiale) alle settimane 26, 52 e 78 per quanto segue:•Tassi di ipoglicemia notturna e totale •Incidenza di ipoglicemia notturna e totale •Cambiamento del peso corporeo dal basale •I profili di auto-monitoraggio glicemico (SMBG) a 9 punti • Dose insulinica basale, bolo e totale (unità e unità/kg)•Trigliceridi |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| [1] Have had T1DM based on the World Health Organization (WHO) classification [2] Are at least 18 years of age [3] Duration of diabetes ≥ 1 year [4] Have an HbA1c value < 12% according to the central laboratory at screening [5] Body mass index ≤ 35.0 kg/m2 [6] Have been treated for at least 90 days prior to screening with insulin (glargine, NPH, or detemir) in combination with pre-meal insulin, or self mixed or pre-mixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or continuous subcutaneous insulin infusion therapy [7] Female patients who are not breastfeeding, test negative for pregnancy at the time of screening and enrollment based on a serum pregnancy test, intend not to become pregnant during the study and have practiced a reliable method of birth control for at least 6 weeks prior to screening; agree to continue to use a reliable method of birth control during the study and for 2 weeks following the last dose of study drug. [8] Have access to a telephone [9] Have refrigeration in the home [10] Capable of, willing and desirous to do the following: adhere to a multiple daily injection regimen, inject insulin with a prefilled pen and perform self blood glucose monitoring and record keeping as required by this protocol, as determined by the investigator. Caregiver may do all of the above. [11] Have given written informed consent to participate in this study in accordance with local regulations. |
| Pazienti di sesso maschile o femminile con diagnosi di T1DM (da almeno 1 anno), di età ≥ 18 anni, con un indice di massa corporea ≤ 35,0 kg/m2. I pazienti devono avere il valore HbA1c < 12,0% allo screening e devono essere stati trattati con una terapia insulinica basale/bolo per almeno 90 giorni prima della Visita 1 con: • insulina detemir, insulina glargine, una sospensione di insulina umana isofano (NPH) in combinazione con insulina pre-pasto, oppure, • regimi insulinici auto-miscelati o pre-miscelati con qualsiasi combinazione di insulina basale/bolo somministrata almeno due volte al giorno, oppure • terapia continua di infusione insulinica per via sottocutanea. I pazienti devono essere disponibili e desiderosi di aderire a regimi multipli di iniezione giornaliera (minimo 3-4 volte al giorno): una somministrazione una volta al giorno di una dose di insulina basale e insulina bolo in caso di consumo superiore al 20% delle calorie giornaliere. |
|
| E.4 | Principal exclusion criteria |
| [12] Are using twice daily insulin glargine having been inadequately controlled on single daily dosed glargine prior to screening. [13] Excessive insulin resistance defined as having received a total daily dose of insulin > 1.5 U/kg at the time of randomization. [14] Receiving any oral or injectable medication (other than metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus other than insulins in the 90 days prior to screening. Note: for subjects on metformin, the following exclusion criteria will apply: have serum creatinine concentration that contraindicates metformin use per the country-specific product labeling; [15] Lipid-lowering medications: are using niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening or are using lipid lowering medication at a dose that has not been stable for ≥ 90 days prior to screening. [16] Have fasting hypertriglyceridemia (defined as >4.5 mmol/L, <400 mg/dl) at screening, as determined by the central laboratory. [17] Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia as determined by the investigator) within 6 months prior to entry into the study. [18] Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or DKA) in the past 6 months. [19] Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association [NYHA] Cardiac Disease Classification). [20] Renal: have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine > 2.5 mg/dL. [21] Hepatic: have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non-alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements of: total bilirubin (≥2 x ULN), or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) >2.5x ULN as defined by the central laboratory or aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) > 2.5 x ULN as defined by the central laboratory. [22] Malignancy: have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator.[23] Allergy: have known hypersensitivity or allergy to any of the study insulins or their excipients. [24] Hematologic: have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c measurement.[25] Glucocorticoid therapy: receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, and inhaled preparations) or have received such therapy within 8 weeks immediately before screening with the exception of replacement therapy for adrenal insufficiency [26] Diagnosed clinically significant diabetic autonomic neuropathy, in the opinion of the investigator. [27] Have any other condition (including known drug or alcohol abuse or psychiatric disorder including eating disorder) that precludes the patient from following and completing the protocol. |
| I pazienti che utilizzano l'insulina glargine due volte al giorno che sono stati controllati inadeguatamente per l'insulina glargine una volta al giorno, nonché i pazienti che stanno ricevendo qualsiasi farmaco antidiabetico per via orale o per iniezioni (diversi da insulina o metformina per malattie ovariche policistiche) prima della Visita 1, saranno esclusi. I pazienti che hanno avuto più di un episodio di ipoglicemia grave o 2 o più visite presso il pronto soccorso o ricoveri a causa dello scarso controllo del glucosio (iperglicemia o chetoacidosi diabetica) nei 6 mesi precedenti la Visita 1, saranno esclusi. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| A change of HbA1c from baseline to 26 weeks that is not inferior to glargine when each is combined with pre-prandial insulin lispro. |
| dimostrare la non inferiorità di LY2605541 iniettato una volta al giorno se confrontato con l’insulina glargine iniettata una volta al giorno, entrambi in combinazione con insulina preprandiale lispro rispetto all’HbA1c a 26 settimane |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Nocturnal hypoglycemia rate; HbA1c; proportion of patients with HbA1c <7.0%; FSG (laboratory measurement); total hypoglycemia rate; total and nocturnal hypoglycemia rates and incidences; weight change from baseline, SMBG 9-point profiles; proportion of patients with HbA1c <7.0%; proportion of patients with HbA1c ≤ 6.5%, proportion of patients with HbA1c < 7.0% without nocturnal hypoglycemia; HbA1c change from baseline; HbA1c at 52 and 78 weeks; basal, bolus, and total insulin doses (units and units/kg); triglycerides (log transformation prior to analysis), total cholesterol, LDL-C, HDL-C; antibodies to LY2605541; FSG by laboratory; FBG (as measured by SMBG), FBG intrapatient variability (as measured by SMBG); 0300-hour BG to fasting BG excursion; ITSQ; LBSS; EQ-5D; RAPA; additional safety endpoints (treatment-emergent adverse events [TEAEs], SAEs, vital signs, treatment exposure, other laboratory measures, etc.) |
| Tasso di ipoglicemia notturna;proporzione di pazienti con HbA1c <7,0%; FSG (misura di laboratorio); tasso ipoglicemia totale; tasso e incidenza di ipoglicemia notturna e totale, variazione di peso dal basale, profilo SMBG a 9 punti, proporzione di pazienti con HbA1c <7,0%, proporzione di pazienti con HbA1c ≤ 6,5%, proporzione di pazienti con HbA1c <7,0% senza ipoglicemie notturna; variazione di HbA1c dal basale; HbA1c a 52 e 78 settimane; dosaggio di insulina basale, bolo, e totale (unità e unità / kg ), trigliceridi, colesterolo totale, LDL-C, HDL-C; anticorpi LY2605541; FBG (misurata in SMBG), escursione della glicemia alle 0300 e a digiuno; ITSQ; LBSS; EQ-5D; RAPA; endpoint di sicurezza supplementare (eventi avversi emergenti dal trattamento [TEAEs],segni vitali, esposizione al trattamento, altre misure di laboratorio, ecc) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| All gated objective endpoints are at 26 weeks of treatment. Nocturnal and total hypoglycemia rates and incidences have various timepoints such as 0 to 2 weeks, 0 to 12 weeks, 0 to 26 weeks, 0 to 52 weeks, 0 to 78 weeks, 2 to 12 weeks, 2 to 26 weeks, 12 to 26 weeks, 12 to 52 weeks, 12 to 78 weeks, 26 to 52 weeks, 52 to 78 weeks; at 52 and 78 weeks for proportion of patients with HbA1c <7.0%, HbA1c and FSG by laboratory; at 26 weeks for ITSQ and EQ-5D, at 26 and 78 weeks for RAPA, and at 26, 52 and 78 weeks for all the other objectives. |
| Tutti gli obiettivi controllati sono a 26 settimane di trattamento.L'incidenza di ipoglicemia notturna e totale hanno riferimenti temporali diversi come ad esempio a 0 e 2 settimane, a 0 e 12 settimane, a 0 e 26 settimane, a 0 e 52 settimane, a 0 e 78 settimane, a 2 e 12 settimane, a 2 e 26 settimane,a 12 e 26 settimane, a 12 e 52 settimane, a 12 e 78 settimane, a 26 e 52 settimane, a 52 e 78 settimane, a 52 e 78 settimane per proporzione di pazienti con HbA1c <7,0%, HbA1c e FSG (laboratorio), a 26 settimane per ITSQ ed EQ -5D, a 26 e 78 settimane per RAPA, e alle settimane 26, 52 e 78 per tutti gli altri obiettivi. |
|
| 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 | Yes |
| 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 | 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 | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| 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 |
| Japan |
| Mexico |
| Russian Federation |
| United States |
|
| 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
|
| Last visit of the last subject undergoing the trial |
| LVLS |
|
| 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 | 28 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 28 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
