| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 19.0 |
| 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 |
| To test whether Mylan’s insulin glargine once daily is non-inferior to Lantus® once daily (based on change in HbA1c from baseline to 24 weeks) when administered in combination with mealtime insulin lispro. |
|
| E.2.2 | Secondary objectives of the trial |
To compare Mylan’s insulin glargine to Lantus®, at 24 weeks and 52 weeks, when administered in combination with mealtime insulin lispro with respect to:
1. Immunogenicity: incidence and change from baseline in the relative levels of ADA, incidence and change from baseline the relative levels of anti-HCP antibodies
2. Rate per 30 days of hypoglycemic events.
3. Occurrence of local reactions, systemic reactions and other adverse events
4. Device-related safety assessment
5. Change in HbA1c from baseline at other scheduled visits
6. Change in fasting plasma glucose from baseline
7. Change in basal insulin dose per unit body weight (U/kg) from baseline
8. Change in 8-point SMBG profile from baseline
9. Proportion of participants with HbA1c <7% at 24 weeks
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written and signed informed consent needs to be provided by patients or their legal representatives before starting any protocol-specific procedures.
2. Male and female patients between the ages of 18 to 65 years, both ages inclusive.
3. Patients with an established diagnosis of T1DM per ADA 2014 criteria who also fulfil the following criteria:
o Initiation of insulin treatment within 6 months of T1DM diagnosis
o Treatment with basal-bolus insulin therapy for at least 1 year before screening
o Fasting plasma C-peptide <0.3 nmol/L at screening
o Patient has been on once daily Lantus® at stable dose (±15% variation in dose) for at least 3 months at screening
4. Body mass index (BMI) of 18.5 to 35 kg/m2 at screening (both values inclusive).
5. Stable weight, with no more than 5 kg gain or loss in the 3 months prior to screening, this information will be collected by patient interview during medical history.
6. Glycosylated hemoglobin (HbA1c) ≤9.5% at screening.
7. Hemoglobin ≥9.0 g/dL at screening.
8. Patient has the capability of communicating appropriately with the investigator.
9. Patient is able and willing to comply with the requirements of the trial protocol including the 8-point self-monitored blood glucose (SMBG), completion of patient diary records and following a recommended diet and exercise plan for the entire duration of the trial.
10. Female patients of childbearing potential who are willing to use oral contraception or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the trial, through trial completion.
• Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Postmenopausal females must have had no regular menstrual bleeding for at least 1 year prior to screening.
• Female patients who report surgical sterilization must have had the procedure at least 6 months prior to screening.
• All female patients of childbearing potential must have negative pregnancy test results at screening and at clinic visits, as per the SCHEDULE OF ACTIVITIES.
• If female patients have male partners who have undergone vasectomy, the vasectomy must have occurred more than 6 months prior to screening
|
|
| E.4 | Principal exclusion criteria |
1. medical condition or disease that in the investigator’s opinion would place the patient at an unacceptable risk from study participation.
2.hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the trial, OR history of significant allergic drug reactions.
3.use of animal insulin within the last 3 years or use of biosimilar insulin glargine at any time prior.
4.use of a regular immunomodulator therapy in the 1 year prior to screening.
5. autoimmune disorders other than T1DM or insufficiently treated autoimmune thyroid disorders (see also exclusion criteria 15), judged clinically relevant by the investigator
6. ≥2 episodes of severe hypoglycemia within the 6 months before screening or history of hypoglycemia unawareness, as judged by the investigator.
7. ≥1 episodes of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening.
8. clinically significant acute bacterial, viral or fungal systemic infections in the last 4 weeks prior to screening
9. Any clinically significant abnormality in ECG or safety laboratory tests conducted at screening and making the patient ineligible for the study (as per investigator).
10. Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg) or hepatitis C (HCVAb) antibodies at screening.
11. History of drug or alcohol dependence or abuse during the 1 year prior to screening.
12. Receipt of another investigational drug in the 3 months prior to screening (or as per local regulations), or if the screening visit is within 5 half-lives of another investigational drug received (whichever is longer), or scheduled to receive another investigational drug during the current trial period.
13. Following secondary complications of diabetes:
• Active proliferative retinopathy as confirmed by a dilated ophthalmoscopy/retinal photography examination performed within the 6 months prior to screening (by a person legally authorized to do so).
• Clinical nephrotic syndrome or diabetic nephropathy with a serum creatinine level >1.5 times of upper limit of reference range at screening
• Severe form of neuropathy (mild and moderate will be included) or cardiac autonomic neuropathy. Patients with mild or moderate forms of neuropathy will be allowed.
• history of limb amputation as a complication of diabetes (at any time), or any vascular procedure during the 1 year prior to screening.
• diabetic foot or diabetic ulcers in the 1 year prior to screening.
14. Any elective surgery requiring hospitalization planned during the trial period.
15. Clinically significant major organ disorder at the time of screening including:
• Uncontrolled hypertension
• Uncontrolled hyperlipidemia
• Uncontrolled hyperthyroidism or hypothyroidism
• Impaired hepatic function. Patients with evidence of Gilberts disease may be included in the trial if they have total bilirubin of <3 mg/dL with indirect bilirubin contributing to >80% of the total bilirubin.
16. History of a significant medical condition, such as:
• Clinically significant cardiac disease like unstable angina, myocardial infarction, grade 3 or 4 congestive heart failure (CHF) according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, and pulmonary hypertension; during the year prior to screening.
• Stroke or transient ischemic attack (TIA) in the 6 months before screening.
17. Patients with major depressive illness in the last 3 years (those who have well controlled depression for 3 months on a stable dose of antidepressants, with no major depressive episodes in the last 3 years, can be included, even if they are on medication), patients with history of other severe psychiatric diseases (manic depressive psychosis [MDP], schizophrenia), which in the opinion of the investigator precludes the patient from participating in the trial
18. History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, sickle cell anemia, etc.).
19. Patients using the following in the 3 months prior to screening:
• Insulin pump therapy
• Any anti-diabetic drugs other than the study insulins allowed by the protocol.
20. Moderate insulin resistance, defined as requiring insulin of ≥1.5 IU/kg/day.
21. Patients who have received ≥14 consecutive days of glucocorticoid therapy by oral, intravenous, or inhaled or other routes that produce systemic effect within the past 1 year, or who have received steroids by any route (except intra-nasal, intra-ocular, and topical) within the 4 weeks immediately preceding screening.
22. Patients diagnosed as having cancer (patients with history of basal cell carcinoma, carcinoma in situ or squamous cell cancer of skin, or in remission >5 years, will be allowed).
23. Patients who have donated blood or plasma in the 1 month prior to screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in HbA1c from baseline to 24 weeks |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Immunogenicity: incidence and change from baseline in the relative levels of ADA, incidence and change from baseline the relative levels of anti-HCP antibodies
2. Rate per 30 days of hypoglycemic events.
3. Occurrence of local reactions, systemic reactions and other adverse events
4. Device-related safety assessment
5. Change in HbA1c from baseline at other scheduled visits
6. Change in fasting plasma glucose from baseline
7. Change in basal insulin dose per unit body weight (U/kg) from baseline
8. Change in 8-point SMBG profile from baseline
9. Proportion of participants with HbA1c <7% at 24 weeks |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At screening, and at study weeks 0, 2, 4, 12, 24, 36 and 52
2. every 30 days
3. at each study visit
4. at each study visit
5. at screening and at study weeks 0, 12, 36 and 52
6. at screening and at study weeks -6, -4, -2, 0, 2, 4, 8, 12, 16, 20, 24, 28, 36, 44, 52
7. at each study visit
8. at each study visit
9. at study week 24 |
|
| 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 | 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 | 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 | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 82 |
| 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 |
| Canada |
| Czech Republic |
| Estonia |
| Germany |
| Hungary |
| Latvia |
| Romania |
| Slovakia |
| South Africa |
| United Kingdom |
| 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
|
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 9 |
Print
