These were the First-In-Human clinical trials of insulin efsitora alfa investigating its safety, tolerability, PK and glucose PD. The single ascending dose (SAD) study over 15 days assessed four different doses (5-35 mg) in 16 healthy trial participants and 57 people with type 2 diabetes (T2D). In the 6-week multiple ascending dose (MAD) trial 33 people with T2D previously treated with basal insulin either received once daily insulin glargine or a one-time loading dose of insulin efsitora alfa followed by once-weekly dosing (1-10 mg).
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Key results of insulin efsitora First-in Human SAD and MAD trial [1]
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SAD trial |
PK half-life of insulin efsitora alfa was approximately 17 days resulting in a sustained dose-dependent decrease in fasting blood glucose for 5 days or more. No severe hygoglycemia occurred.
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MAD trial |
Low peak-to-trough ratio of insulin efsitora alfa of 1.14 after the last dose at week 6 (steady state). Over the 6-week period 7-point glucose profiles remained constant and similar to insulin glargine. Rates and duration of hypoglycemic events were also comparable to insulin glargine. |
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Conclusion |
Insulin efsitora alfa was well tolerated and exhibited a PK/PD profile suitable for once-weekly dosing.
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This randomized, open-label, crossover trial investigated the PK and PD characteristics of once weekly basal insulin icodec after single subcutaneous (s.c.) injections (5.6 U/kg) in the thigh, abdomen or upper arm in 25 individuals with type 2 diabetes. Frequent PK sampling was performed until 35 days post-dose.
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Key results of once-weekly basal insulin icodec administered as single dose to three different injection regions (abdomen, thigh, upper arm) [2] |
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Total icodec exposure (AUC0-∞,SD)
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Was similar between injection in the abdomen, thigh and upper arm |
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Maximum icodec concentration (Cmax) |
Was higher for abdomen (by 17%, p=0.002) and upper arm (by 24%, p<0.001) versus thigh. When simulated to steady state, smaller differences in Cmax were seen for abdomen (by 11%, p=0.004) and upper arm (by 16%, p<0.001) versus thigh |
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Geometric mean glucose- lowering effect 36-60 h post-dose
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Was comparable for thigh, abdomen and upper arm |
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Conclusion |
Icodec can be administered s.c. in the thigh, abdomen or upper arm with no clinically relevant difference in exposure and with a similar glucose-lowering effect. |
This randomised, double-blind, two-period crossover trial compared prandial administration of ADO09 or insulin aspart over 24 days in trial participants with type 1 diabetes in a low-dose (LD) group (n=28; ≤40 U bolus insulin per day) versus a high-dose (HD) group (n=16, 40-75 U bolus insulin per day). Glucodynamics through continuous glucose monitoring (CGM) as well as PK/PD profiles following mixed-meal tolerance tests (MMTT) were evaluated at baseline and end of treatment.
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Key results of the ADO09 versus insulin aspart trial in T1D [3] |
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Glucose increments from 0 to 4 h following MMTT
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Were 39% (not statistically significantly) lower with ADO09 in the low-dose group and 69% lower in the high-dose group. |
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Mean CGM glucose during ambulatory treatment |
Was lower with ADO09 than with insulin aspart (LD: -8.2 ± 7.9 mg/dl; HD: -7.0 ± 10 mg/dl)
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Time in range (70-180 mg/dl)
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Improved in both LD and HD group by +4% |
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Body weight (kg)
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Declined significantly with ADO09 (LD: -0.8 kg; HD: -1.6 kg) |
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Hypoglycemic events
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Were more frequent with ADO09 versus insulin aspart (LD: 142 vs 115 events; HD: 96 vs 79)
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Conclusion |
Compared to insulin aspart, ADO09 was well tolerated and effective in a wide range of dosage, significantly improving the average BG level and body weight during 24 days of ambulatory treatment. Meal test profiles confirmed these improvements of glycemic patterns and other responses with ADO09.
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The aim of this trial was to establish PK and PD equivalence of Biocon’s biosimilar insulin N with US-licensed Humulin® N in 90 healthy subjects (85 completers). The design was a single-centre, randomised, double-blind, three-period, six-sequence, partially replicated, 24-hour euglycemic clamp study.
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Key results of Biocon’s biosimilar insulin N PK/PD equivalence euglycemic clamp trial vs Humulin N [4] |
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Primary PK endpoints:
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Equivalence established. |
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Primary PD endpoints:
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Equivalence established. |
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Conclusion |
PK and PD equivalence was shown between Biocon’s biosimilar insulin N and Humulin® N in healthy subjects and both treatments were well tolerated and considered safe. |
This phase 1 clinical trial evaluated the effect of meloxicam on insulin lispro PK and glucose PD over 10 days of continuous subcutaneous insulin infusion (CSII) at one infusion site in trial participants with type 1 diabetes. The study design was double-blind, two-way crossover. 20 participants randomly received U100 insulin lispro and U100 Insulin lispro + 0.25 mg/mL meloxicam (LY900027).
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Key results of Insulin lispro PK and PD + meloxicam [5]
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AUC Ins0-5h after bolus administration prior to a MMTT
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Was significantly lower on Day 10 versus Day 3 for LY900027 (-19%) and insulin lispro (-14%); the AUC INS0-5h did not differ significantly between treatments. |
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C INS.max |
Increased with LY900027 and insulin lispro (by ~14%-23% and ~16%-51%) on days 5, 7 and 10 vs Day 3. The C INS.max of LY900027 was ~14-23% lower than that of insulin lispro on Days 7 and 10.
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Conclusion |
The PK of insulin changed over catheter wear time even when an anti-inflammatory agent was present. Postprandial glycemic control was adversely affected by the accelerated insulin absorption and decreased insulin exposure.
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