OGLUO Solution for injection Ref.[50398] Active ingredients: Glucagon

Pharmacotherapeutic group: Pancreatic hormones, glycogenolytic hormones: H04AA01

Mechanism of action

Glucagon is a hyperglycaemic agent that mobilises hepatic glycogen, which is released into the blood as glucose. Hepatic stores of glycogen are necessary for glucagon to produce an anti-hypoglycaemic effect.

Pharmacodynamic effects

After administration of 1 mg Ogluo in adult patients with diabetes, the mean maximum plasma glucose increase from baseline was 176 mg/dL. After administration, plasma glucose begins to rise as early as 5 minutes. From the time of injection, the mean time to plasma glucose >70 mg/dL or ≥20 mg/dL increase was 14.8 (±5.3) minutes.

Clinical efficacy and safety

Ogluo was evaluated in 132 adult patients aged 18 to 74 years with type 1 diabetes in a multicentre randomised, active-controlled, single-blind, 2-way crossover study. The study involved 2 clinic visits 7 to 28 days apart, with random assignment to receive glucagon 1 mg solution for injection during one session and reconstituted glucagon 1 mg powder and solvent for solution for injection during the other. A total of 127 subjects received an injection of Ogluo and 123 subjects received a glucagon powder and solvent for solution for injection.

The efficacy of glucagon 1 mg solution for injection was compared to reconstituted glucagon 1 mg powder and solvent for solution for injection in subjects who were in a state of insulin-induced hypoglycaemia with target plasma glucose less than 3.0 mmol/L (<54 mg/dL). Treatment ‘success’ was defined as plasma glucose increase from time of glucagon administration to absolute value greater than 3.89 mmol/L (>70 mg/dL) or relative increase of 1.11 mmol/L (≥20 mg/dL) or greater, within 30 minutes after glucagon administration. The proportion of patients who achieved treatment ‘success’ was 99.2% in the glucagon 1 mg solution for injection group and 100% in the reconstituted glucagon 1 mg powder and solvent for solution for injection group, and the comparison between groups met the prespecified non-inferiority margin.

From the time of administration, which does not include the preparation time for each medicinal product prior to administration the mean time to treatment ‘success’ was 14.8 (±5.3) minutes in the glucagon 1 mg solution for injection group and 10.4 (±1.8) minutes in the reconstituted glucagon 1 mg powder and solvent for solution for injection group. From the time of decision to dose, which includes the preparation time for each medicinal product prior to administration, the mean time to treatment ‘success’ was 15.6 (±5.2) minutes in the glucagon 1 mg solution for injection group and 12.2 (±2.0) minutes in the reconstituted glucagon 1 mg powder and solvent for solution for injection.

Paediatric population

Ogluo was evaluated in 31 pediatric patients ages 2 to 18 years (7 patients in the 2-<6, 13 patients in the 6-<12 and 11 patients in the 12-<18 years old group) with T1DM in an open-label, sequential, uncontrolled clinical study. Efficacy was assessed based on increases from Baseline in mean plasma glucose 30 minutes post-dosing. Statistically significant changes from Baseline of 81.4 mg/dL [SD=18.3], 84.2 mg/dL [SD=25.3], and 54.0 mg/dL [SD=27.3] were observed in the 2-< 6 years, 6-<12 years, and 12-< 18 years [1 mg dose] age groups, respectively). Across all 31 subjects the mean time to plasma glucose increase ≥25 mg/dL from baseline was 18.9 minutes.

In paediatric patients with type 1 diabetes (2 to <18 years), the mean maximum glucose increase from baseline was 134 mg/dL (2 to <6 years), 145 mg/dL (6 to <12 years), and 123 mg/dL (12 to <18 years).