Efficacy of MM005-Granulae as prophylaxis for nocturnal hypoglycemia in insulin treated Type 1 diabetic subjects. A double-blind, randomized, placebo-controlled phase II multi-center study in three parallel arms.

INTERVENTION: Product Name: MM005‐Granulae Product Code: MM005‐Granulae Pharmaceutical Form: Granules INN or Proposed INN: Maydis amylum (Corn starch) CAS Number: 9005‐28‐8 Other descriptive name: uncooked cornstarch Concentration unit: g gram(s) Concentration type: equal Concentration number: 20‐ INN or Proposed INN: Maydis amylum (Corn starch) CAS Number: 9005‐25‐8 Other descriptive name: Uncooked cornstarch Concentration unit: g gram(s) Concentration type: equal Concentration number: 30‐ Pharmaceutical form of the placebo: Granules Route of administration of the placebo: Oral use CONDITION: Diabetes type I ; MedDRA version: 6,1 Level: LLT Classification code 10045228 PRIMARY OUTCOME: Main Objective: 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. 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. Secondary Objective: (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.; 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) Are the trial subjects under 18? no Number of subjects for th