Study designs

The Heise, Hermanski, et al Study3

Population: Adults with type 1 diabetes.

Study design: Randomized, double-blind, parallel-group, single-center trial evaluating the within-subject, day-to-day variability and glucose-lowering effect of Tresiba® U-100 (n=27) vs insulin glargine U-100 (n=27) under steady-state conditions. Patients received Tresiba® U-100 or insulin glargine U-100 (0.4 units/kg) once daily for 12 days. The euglycemic clamp was performed on days 6, 9, and 12 of treatment and blood samples were taken throughout each clamp period.

Primary endpoint: To evaluate the within-subject variability of the PD response between Tresiba® U-100 and insulin glargine U-100 based on the area under the glucose infusion rate curve (AUCGIR) during 1 dosing interval (0-24 hours) at steady state. The within-subject, day-to-day PD variability in glucose-lowering effect in the Tresiba® arm was 20% and in the insulin glargine U-100 arm was 82% at steady state.

Secondary PD endpoints: To investigate whether within-subject variability was consistent over 24 hours, the within-subject of AUCGIR in 2-hour intervals (AUCGIR,0-2h,SS’ AUCGIR,2-4h,SS’ AUCGIR,4-6h,SS’ AUCGIR,20-22h,SS’ AUCGIR,22-24h,SS) was analyzed in a post-hoc analysis.

The Heise, Korsatko, et al Study2

Population: Adults with type 1 diabetes or type 2 diabetes.

Study design: Post hoc analysis of 5 randomized, double-blind, single-center, phase 1 trials. Patients (n=195) received once-daily doses ranging from 0.4-0.8 U/kg and for 6-12 days, depending on the individual study.

Primary endpoint: Determining the duration and consistency of time to steady state Tresiba® U-100 following once-daily subcutaneous dosing in subjects of varying age and diabetes type.

AUCGIR,0-24h,SS=area under the GIR curve from 0 to 24 hours at steady state; CV=coefficient of variation; PK/PD=pharmacokinetic/pharmacodynamics.