E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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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 |
To evaluate the safety and immunogenicity of Insugen R plus Insugen N compared to European Union (EU) sourced Actrapid plus Insulatard in patients with Type 1 diabetes mellitus. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of Insugen R plus Insugen N compared with EU sourced Actrapid plus Insulatard in patients with Type 1 diabetes mellitus. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provide written informed consent 2. Male and female patients between the ages of 18 to 80 years, inclusive 3. Patient must have been diagnosed with T1DM before 40 years of age and must have been on treatment with insulin for at least one year (confirmed by interview with the patient). Patients should have a fasting plasma C-peptide </= 0.2 pmol/mL (</= 0.6 ng/mL or </= 0.2 nmol/L) and/or a history of initiation of insulin treatment within 6 months after diagnosis 4. At least 3 months on basal-bolus insulin therapy before enrolment requiring 3 or more daily injections 5. Body mass index of 18.5 to 34.99 kg/m2, inclusive 6. Stable weight with no more than 5 kg gain or loss within 3 months of Screening (obtained by patient history) 7. Glycosylated haemoglobin (HbA1c) ≤ 11.0% at Screening. One (1) re-test is permitted within the Screening timeline, if required. 8. Ability and willingness to perform blood glucose profiles using blood glucose meter at home during the study |
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E.4 | Principal exclusion criteria |
1. History of hypersensitivity to any of the active or inactive ingredients of the test and/or reference products 2. A clinically significant abnormality (including laboratory values) at Screening, on the basis of which the Investigator advises against study inclusion 3. An electrocardiogram (ECG) abnormality at Screening considered clinically significant by the Investigator 4. Use of insulin pump therapy in the past 2 months before Screening 5. Moderate insulin resistance defined as requiring insulin of >/=1.4 IU/kg/day 6. Significant history of atopy or allergic drug reactions 7. Clinically significant major organ disease before Screening, except for well-controlled and stable conditions such as essential hypertension (blood pressure >130/80 mmHg), well controlled hyperlipidaemia, and thyroid disorders for at least 3 months before Screening. 8. Knowledge of secondary complications of diabetes: a. Retinopathy: moderate to severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy of any severity or history of treatment with laser surgery/vitrectomy within 6 months of the Screening visit b. Nephropathy: Proteinuria ≥1+ by urine dipstick in the absence of infection or vaginal contamination and/or serum creatinine ≥1.5 times of upper limit of reference range, one (1) re-test is permitted within the Screening timeline, if required; history of renal transplant c. Neuropathy: History or finding of severe form of sensorimotor, cardiac, gastrointestinal, or genitourinary autonomic neuropathy d. Peripheral vascular disease (PVD): Severe PVD that has resulted in amputation, chronic foot ulcer, claudication on walking <200 metres, or absent pulses 9. Unstable coronary artery disease (unstable angina, myocardial infarction within the preceding 6 months), heart failure (New York Heart Association Grade 2 or higher), history of stroke, or transient ischemic attack within the preceding 6 months 10. History of drug or alcohol dependence or abuse within 6 months before Screening 11. Current use of systemic or inhaled glucocorticoids or other drugs which may affect glycaemic control 12. Treatment with blood-glucose lowering drugs other than insulin or insulin analogues in the last 4 weeks before Screening or during the study 13. The use of prohibited concomitant medications, including oral hypoglycaemic agents; monoamine oxidase (MAO) inhibitors; Beta blockers; salicylates >300 mg/day or chronic usage requiring uninterrupted administration for >14 days during the study; anabolic steroids; diltiazem; niacin; isoniazid; epinephrine; thiazide diuretics if >25 mg/day; and loop diuretics. 14. History of 2 or more episodes of hypoglycaemia requiring assistance by another person to administer glucose or glucagon (severe hypoglycaemia) within 6 months before Screening 15. Any hospitalisation or emergency department visit due to poor diabetes control within 6 months before Screening 16. Any electively planned surgery requiring hospitalisation 17. Pregnancy, breastfeeding, or planned pregnancy during the study duration. Women of childbearing potential (any woman who is not surgically sterile or > 2 years post menopause) must agree to use a reliable method of contraception (e.g., double-barrier, tubal ligation, or stable hormonal contraception) throughout the study period. Women who become pregnant during the study must be discontinued from the study and followed for pregnancy outcome 18. Impaired hepatic function (alanine transaminase [ALT] or aspartate aminotranferase [AST] value > 2 times the upper limit of the reference range and/or serum bilirubin >1.5 times the upper limit of the reference range at the Screening visit). One (1) re-test is permitted within the Screening timeline, if required. 19. Impaired renal function (serum creatinine ≥1.5 times of upper limit of the reference range at Screening) or chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73m2) 20. Haemoglobinopathies, haemolytic anaemia, anaemia of chronic disease, or any factor affecting the measurement of HbA1c 21. Receipt of another investigational drug within 6 weeks before Screening or within 5 half-lives of the drug, whichever is longer, or scheduled treatment of another investigational drug during the current study period 22. Any patient who in the estimation of the Investigator does not show necessary compliance to participate in the trial and comply with necessary trial requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints phase 1: Comparison of the change in mean anti-insulin antibody binding percentage from Baseline to Week 24 between Insugen R plus Insugen N and Actrapid plus Insulatard groups.
Primary endpoints phase 2: Change in mean anti-insulin antibody binding percentage from Baseline (Visit 3) to the end of Week 48. |
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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 | Yes |
E.6.8 | Bioequivalence | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Blinded endpoint analysis |
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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.8.3 |
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 | 22 |
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 | Information not present in EudraCT |
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 |
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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
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End of trial is defined as the last visit of the last patient undergoing the trial. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |