Table 1.
Acceleration of Pharmacokinetic Responses by Recombinant Human Hyaluronidase across Eight Studies
| Study | Early exposure (% of analog alone)a | Cmax (% of analog alone) | tmax (difference from analog alone) | % of total AUC beyond 2 h (% of analog alone) |
|---|---|---|---|---|
| Proof of conceptb | 255% | 190% | -49 min | 69% |
| Comprehensive analogc | 291% | 210% | -26 min | 53% |
| rHuPH20 dose selection studyd | 177% | 163% | -20 min | 28% |
| Variability studye | 206% | 162% | -16 min | 47% |
| Type 1 meal studyf | 154% | 135% | -18 min | 43% |
| Type 2 meal studyg | 216% | 174% | -31 min | 76% |
| CSII comixture (initial clamp)h | 166% | 161% | -8 min | 61% |
| CSII pretreatment (initial clamp)i | 206% | 129% | -49 min | 61% |
Early exposure = % of total in first 60 min.
Twelve healthy volunteers given 20 U insulin lispro diluted to a concentration of 91 U/ml ± rHuPH20 at 11.3 µg/ml.18
Fourteen healthy volunteers given 0.15 U/kg insulin lispro diluted to 95 U/ml ± rHuPH20 at 5 µg/ml.20
Twelve healthy volunteers given 6 U insulin lispro diluted to 25, 50, or 95 U/ml ± rHuPH20 at 5 µg/ml.21
Twenty healthy volunteers given 0.15 U/kg insulin lispro diluted to 40 U/ml ± rHuPH20 at 5 µg/ml.22
Twenty-one subjects with type 1 diabetes given individually dose-optimized doses (mean dose = 5.7 U) of insulin lispro diluted to 91 U/ml + rHuPH20 at 18.2 µg/ml followed on a separate occasion by the same dose of insulin lispro alone.4
Twenty-one subjects with type 2 diabetes given individually dose-optimized doses (mean dose = 25.2 U for lispro + PH20, 27.3 U for insulin lispro alone) of insulin lispro diluted to 95 U/ml ± rHuPH20 at 5 µg/ml, comparison of pharmacokinetic parameters performed on a dose-normalized basis since doses were not identical for different treatments.5
Sixteen subjects with type 1 diabetes using CSII given 0.15 U/kg of insulin aspart (100 U/ml) ± rHuPH20 at 5 µg/ml after 12 h of infusion site use.19
Fifteen subjects with type 1 diabetes given 0.15 U/kg of insulin aspart (100 U/ml) after 2 h of infusion site use; either 150 U (1.25 µg) rHuPH20 pretreatment of the infusion site or sham injection had previously been performed immediately upon placement of the infusion set.23