Date: 2014-09-09
Type of information: Interim results
phase: 2a
Announcement: interim results
Company: Adocia (France)
Product: BioChaperone® Lispro U100
Action mechanism:
Disease: type 1 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial details:
Latest
news: * On September 9, 2014, Adocia announced positive preliminary results from a Phase IIa dose-response clinical trial evaluating its innovative ultra-fast formulation of insulin lispro (BioChaperone Lispro U100) tested at three doses, relative to Eli Lilly’s Humalog® commercial insulin (insulin lispro U100). This dose response study confirms that BioChaperone Lispro U100 more closely mimics the endogenous insulin secretion observed in healthy individuals in response to a meal than Humalog®, at all tested doses. BioChaperone Lispro U100 has now been tested in 73 patients (for a total of 149 injections) and was very well tolerated. Clinical results confirm the ultra-fast action of BioChaperone Lispro U100 and show a dose-response effect. In this double-blind, randomized, four-period cross-over study, the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of BioChaperone Lispro at three doses were compared to those of Humalog at a single dose. 37 patients with type 1 diabetes received three increasing doses of BioChaperone Lispro (0.1 U/kg, 0.2 U/kg and 0.4 U/kg ) and one dose of Humalog (0.2 U/kg) under automated euglycemic clamp conditions (ClampArt®, target blood glucose (BG) 100 mg/dL, clamp duration 12 hours post-dosing).
All BioChaperone Lispro dosages were well tolerated and did not induce any local reaction, while Humalog was associated to an injection site erythema in one patient.
In pharmacokinetics, BioChaperone Lispro showed a significantly faster rate of insulin lispro absorption than Humalog with an increase in the early insulin exposure of 136% at the same dose (AUClispro_0-30min 25 ± 10 vs. 12 ± 7 h*mU/L; p<0.001). The time to peak insulin lispro concentration was significantly reduced (median Tmax 40 vs. 60 min; p=0.001). BioChaperone Lispro was also cleared from the blood significantly earlier than Humalog, reflected in the time to half-maximum insulin levels after Tmax (late T50%max = 132 ± 41 vs. 163 ± 49 min, p<0.001).
The acceleration of insulin lispro absorption with BioChaperone translated into a significant acceleration of its metabolic effect. The early metabolic effect was increased by more than 70% relative to Humalog during the first hour after administration (AUCGIR_0-1h = 207 ± 87 vs. 123 ± 58 mg/kg; p<0.0001).
Finally, the total insulin exposure and potency of insulin lispro were similar for both formulations.
In a comparable clinical setting, BioChaperone Lispro had already shown superior PK/PD profiles vs. Humalog. The reproducibility of this second clinical study confirms the robustness of the product performance.
The primary objective of this study was to investigate the dose-exposure and the dose-response relationships of BioChaperone Lispro at 0.1, 0.2 and 0.4 U/kg.
A dose proportionality relationship was demonstrated for the total insulin exposure and the maximum insulin lispro concentration (AUC0-last = 112, 213 and 452 h*mU/L and Cmax = 55, 100 and 191 mU/L for 0.1, 0.2 and 0.4 U/kg respectively).
A linear dose response relationship was demonstrated for the total metabolic effect and the maximum glucose infusion rate (AUCGIR0-last = 726, 1357 and 2422 mg/kg and GIRmax = 4.8, 7.4 and 10.2 mg/kg/min for 0.1, 0.2 and 0.4 U/kg respectively).
The ultra-fast absorption of insulin lispro for all doses of BioChaperone Lispro is confirmed by constant time-related parameters, such as time to early maximal observed insulin lispro concentration (early T50%max = 15±5, 15±5 and 15±5 min at 0.1, 0.2 and 0.4 U/kg respectively).
“This solid clinical evidence confirms that BioChaperone Lispro U100 is a compelling ultra-fast-acting insulin across the usual therapeutic dose range,” said Olivier Soula, Deputy General Manager and R&D Director at Adocia, “We are now confident that the clinical development path is straightforward, as the product combines a high level of performance with a solid safety and stability profile. The key next step is to establish the medical benefit, which we intend to do with a meal study in Type 1 diabetics using insulin pumps beginning in Q1 2015.” Adocia will be present at the 50th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria from the 15-19th September 2014, to present two posters on Phase IIa clinical data previously obtained with BioChaperone Lispro and BioChaperone Glargine Lispro Combo.
