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 | 6,1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
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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 |
The primary objective is to assess the efficacy of MM005-Granulae in doses of 20 g and 30 g compared to placebo as prophylaxis for nocturnal hypoglycemia in insulin treated Type 1 diabetic subjects with a history of biochemical hypoglycemic events. |
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E.2.2 | Secondary objectives of the trial |
(1) To assess the safety and tolerability of MM005-Granulae (2) To assess the change from baseline in HbA1C after eight weeks’ treatment with MM005-Granulae compared to placebo (3) To assess the change from baseline in HbA1C, comparing MM005-Granulae and placebo at follow-up, i.e. 30-37 days after end of treatment. (4) To assess the change from baseline in the lipid profile (cholesterol, LDL and HDL cholesterol, triglycerides and apolipoproteins A1 and B) after eight weeks’ treatment with MM005-Granulae compared to placebo (5) To assess the proportion of time with P-glucose <3.3 mmol/L during the six nights with CGMS recordings.
All comparisons will be performed (a) between active treatment and placebo and (b) between 20 g, 30 g and placebo.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Age ≥ 20 to ≤ 70 years 2. Informed consent given and signed 3. Type 1 diabetes, treated with short acting insulin (including insulin analogues) and or intermediate- and or long acting insulin (including insulin analogues). 4. A history of hypoglycemic events, i.e. subjects who regularly (at least 4 times/month during the last 3 months) experience plasma glucose < 3.3 mmol/L, corresponding to blood glucose <3.0 mmol/L 5. Duration of diabetes ≥3 years 6. BMI ≥ 19 to < 30 (kg/m2) 7. HbA1c ≤ 8.5 % (based on sample taken at enrollment visit) 8. C-peptide < 0.17 nmol/L (based on sample taken at enrollment visit) unless the diagnosis has been similarly confirmed and documented before 9. Compliance of at least 65%* during run-in period(*depending on length of the run-in period, this means medication taken for at least 4 out of 5 days, 4 out of 6 days or 5 out of 7 days)
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E.4 | Principal exclusion criteria |
1. Clinically significant symptoms of autonomic neuropathy experienced by the subject 2. Untreated proliferative retinopathy 3. Nephropathy (P-creatinine ≥ 150 mmol/L based on sample taken at enrollment visit) 4. Use of medication known to influence gastrointestinal motility (presently or during the past 4 weeks) 5. Untreated hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 95 mm Hg) 6. Cardiac insufficiency (severity grade II or higher according to NYHA) 7. Ischemic heart disease (severity grade II or higher according to NYHA) 8. Pregnancy* or lactation or intention to become pregnant during the study period.(*Women of childbearing potential are excluded unless a negative test for pregnancy has been obtained.) 9. Increased liver enzymes (ASAT or ALAT or alkaline phosphatase or bilirubin 2.5 times above the upper reference value based on sample taken at enrollment visit) 10. Suspected alcohol or drug abuse 11. Inability to understand information or comply with the study procedures 12. Participation in another clinical intervention study within 30 days prior to enrollment 13. Gastrointestinal inflammatory diseases including celiaki 14. Untreated hypothyroidism (diagnosed by TSH assay based on sample taken at enrollment visit)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of nights (23.00-07.00) with at least one biochemical hypoglycemic event (P-glucose <3.3 mmol/L, corresponding to B-glucose<3.0 mmol/L) captured by Continuous Glucose Monitoring System (CGMS) during two periods (each consisting of three consecutive nights) during week 4 and 8 of treatment with MM005-Granulae or placebo. |
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | 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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 trial is defined as last visit (visit 7 - follow-up visit) of the last subject 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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |