Date: 2015-02-05
Type of information: Initiation of preclinical development
phase: 2a
Announcement: clinical trial authorisation
Company: Adocia (France)
Product: HinsBet® (fast-acting human insulin)
Action
mechanism: rapid-acting insulin. Adocia has developed its fast-acting insulin HinsBet® using its BioChaperone library of polysaccharides modified with naturally occurring molecules. BioChaperone is designed to form a reversible molecular complex with therapeutic proteins in order to solubilize and stabilize these proteins and to control their delivery.
Disease: type 1 diabetes
Therapeutic area: Metabolic diseases
Country: Germany
Trial details:
Latest
news: * On February 5, 2015, Adocia announced positive results from a Phase IIa clinical trial evaluating its innovative fast-acting
formulation of recombinant human insulin, HinsBet, in comparison to Eli Lilly’s commercial products, Humalog® (insulin lispro) and Humulin® (recombinant human insulin). Adocia’s HinsBet formulation incorporates proprietary BioChaperone® technology which enables accelerated absorption of prandial insulins. The present study met its primary endpoint, measuring the increase of recombinant human insulin bioavailability during the first hour for HinsBet as compared to Humulin. The main objective for prandial insulins is to mimic physiological response to a meal with an absorption of subcutaneous insulin as fast as possible. Therefore, the effect of prandial insulins in the first hour is critical. These clinical results show that HinsBet has an early effect equivalent to that of a fast-acting insulin analog, Humalog, and twice superior to that of regular recombinant human insulin, Humulin.
In this double-blind crossover study, the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of HinsBet were compared to those of Humulin and Humalog. Thirty-six patients with type 1 diabetes received single 0.2 U/kg doses of HinsBet, Humulin and Humalog under automated euglycemic clamp conditions (ClampArt®, target blood glucose (BG) 100 mg/dL, clamp duration ten hours post-dosing). All three formulations were well tolerated and did not induce any local reaction. HinsBet had a significantly faster rate of absorption than Humulin with an increase in the early insulin exposure of 70% (primary endpoint, AUCins_0-1h 26.0 ± 14.3 vs. 15.5 ± 9.7 h*mU/L; p<0.0001). The acceleration of human insulin absorption with BioChaperone translated into a significant acceleration of its action. Indeed, the metabolic effect is triggered significantly earlier for HinsBet than for Humulin with a 70% shorter onset of action (Tonset = 28 ± 10 vs. 49 ± 20 min; p<0,0001). Moreover, the metabolic effect of HinsBet is more than twice the one of Humulin in the first hour post-administration (AUCGIR_0-1h = 111 ± 63 vs. 46 ± 52 mg/kg;
p<0,0001).
Finally, the total insulin exposure and potency of recombinant human insulin was similar for both HinsBet and Humulin with no significant difference (AUCins_0-last = 158 ± 47 vs. 152 ± 33 h*mU/L and AUCGIR_0-last = 1294 ± 611 vs. 1256 ± 613 h*mU/L). In comparison to Humalog, HinsBet demonstrated a similar absorption rate to Humalog with no significant difference in early exposure (AUCins_0-30min 10.7 ± 6.3 vs. 11.5 ± 9.6 h*mU/L). This similar absorption also translated into a similar early metabolic effect between HinsBet and Humalog (AUCGIR_0-1h = 111 ± 63 vs. 130 ± 80 mg/kg).* On July 9, 2014, Adocia announced that BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte), the German regulatory agency for drugs and medical devices, has approved the initiation of a Phase IIa clinical study of HinsBet®, a fast-acting formulation of human insulin. The aim of this Phase IIa clinical trial is to demonstrate that HinsBet® acts faster than Humulin® (human insulin, Eli Lilly) and as fast as Humalog® (insulin lispro, Eli Lilly), allowing patients who use human insulin to achieve a better glycemic control after a meal. In this double-blind, randomized, 3 arm, crossover study, the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of HinsBet will be compared to those of Humulin® and Humalog®. 36 patients with type 1 diabetes will receive single 0.2 U/kg doses of HinsBet®, Humulin® and Humalog® under automated euglycemic clamp conditions. Adocia plans to dose the first patient during the first week of August. Results are expected in Q1 2015.
