E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 1 |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
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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 test the hypothesis that LY900014 is noninferior to Humalog on glycemic control (NIM=0.4% for HbA1c) in patients 1 to <18 years of age with T1D when administered as prandial insulin in combination with basal insulin as part of a multiple daily injection regimen for 26 weeks |
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E.2.2 | Secondary objectives of the trial |
-To test the hypothesis that LY900014 administered as postprandial insulin up to 20 minutes after the start of a meal (LY900014+20) is noninferior to Humalog, administered as prandial insulin (0 to 2
minutes prior to the meal), on glycemic control (NIM=0.4% for HbA1c)
-To test the hypothesis that LY900014 is superior to Humalog in improving glycemic control (HbA1c) when administered as prandial insulin (0 to 2 minutes prior to the meal)
-To compare LY900014, LY900014+20, and Humalog with respect to the incidence and rate of documented post-dose hypoglycemia |
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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 |
Protocol Addendum I8B-MC-ITSB(3) A Prospective, Randomized, Double-Blind Comparison of
LY900014 to Humalog with an Open-Label Postprandial LY900014 Treatment Group in Children and Adolescents with Type 1 Diabetes, PRONTO-Peds, 28.November2018
The primary objective of this addendum (I8B-MC-ITSB [3]) is to compare LY900014 and
Humalog, when administered as prandial insulin (0 to 2 minutes prior to the start of a meal), with
respect to the incremental glucose AUC 0-2hours after the start of meals obtained from up to
10 days of CGM use at Week 26.
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E.3 | Principal inclusion criteria |
[1] Male or female patients with T1D for at least 6 months and diagnosed by an endocrinologist (pediatric or adult), diabetes specialist, or a physician with expertise in treating pediatric patients with Type 1 diabetes.
[2] Are at least 1 to <18 years of age.
[4] Have been treated with only one of the following rapid-acting insulin analogs as part of an MDI regimen for at least the last 90 days:
a. insulin lispro U-100, or
b. insulin aspart
c. insulin glulisine or
d. Fast acting insulin aspart (must be approved for use in children in accordance with the local product label)
[5] Have been treated with only one of the following basal insulins for at least the last 90 days:
a. insulin glargine U-100 (QD or BID), or
b. insulin detemir U-100 (QD or BID), or
c. insulin degludec U-100 (QD)
[6] Use a total daily dose of insulin 0.5 to ≤1.5 U/kg.
a.TDD can be the average of previous 3 to 7 days
[7] Have an HbA1c value ≥6.5 and ≤9.5%, according to the central laboratory. |
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E.4 | Principal exclusion criteria |
[13] Have current hypoglycemic unawareness in the investigator’s opinion or have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia, indicated by coma or convulsion and/or use of intravenous glucose or glucagon) within 6 months prior to screening (Visit 1).
[14] Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within 6 months prior to screening (Visit 1).
[15] Have any other clinically significant disorder or uncontrolled concomitant disease that, in the investigator's opinion, would preclude participation in the trial or pose a safety risk.
[24] Receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, and inhaled preparations) or have received such therapy within the last 90 days.
[25] Have been on a treatment regimen that includes regular human insulin, neutral protamine Hagedorn (NPH), Afrezza® (insulin human) inhalation powder, any premixed insulins or use of diluted insulins within the last 90 days.
[26] Receiving any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins within the last 90 days.
[27] Have been treated by CSII regimen for ≥14 days within the last 90 days.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Difference between LY900014 and Humalog in change from baseline to Week 26 in HbA1c
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change from baseline to Week 26 in HbA1c
• Difference between LY900014 and Humalog in change from baseline to Week 26 in HbA1c
• Rate (events/patient/year) and incidence (percentage of patients with events) of documented post-dose hypoglycemic events within 1 and 2 hours after the prandial dose from Weeks 0 through Week 26 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Rate (events/patient/year) and incidence (percentage of patients with events) of documented post-dose hypoglycemic events within 1 and 2 hours after the prandial dose from Weeks 0 through 26 |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Austria |
Brazil |
China |
Czech Republic |
Denmark |
France |
Germany |
Israel |
Italy |
Japan |
Mexico |
Poland |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
United States |
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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
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End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of
Activities for the last patient. |
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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 | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 17 |