Conditions: Type 1 Diabetes Mellitus
Keywords: Recombinant Hyaluronidase Type 1 Diabetes Mellitus Humalog Humulin R rHuPH20 Hylenex
Allocation:  | Intervention model: CROSSOVER
Enrollment: 22
Healthy volunteers: no

Brief summary:
Humalog and Humulin-R (recombinant human insulin) are Food and Drug Administration (FDA) approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase PH20 (rHuPH20) is approved by the FDA for use as an aid in the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both Humalog and Humulin-R in order to determine if it improves the absorption of these insulins to more closely mimic the body's natural increase in insulin in response to a meal.

Detailed description:
Participants received all 4 interventions in the same order.

Dose-finding visits were conducted to identify the appropriate dose of Humalog and Humulin-R. For each Humalog dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humalog, corresponding to a mass concentration of 18.2 micrograms per milliliter (μg/mL) rHuPH20 (at final concentration of 91 U/mL of Humalog). For each Humulin-R dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humulin-R, corresponding to a mass concentration of 20.0 μg/mL rHuPH20 (at final concentration of 100 U/mL of Humulin-R).

Arms:
arm 1: Humalog + Recombinant human hyaluronidase PH20 (rHuPH20) (Intervention 1): 24 units (U) of rHuPH20 per unit of Humalog, injected subcutaneously (SC), for up to 3 visits until an appropriate dose was identified.

Humalog alone (Intervention 2): a single SC injection of the appropriate identified dose of Humalog, delivered before a liquid meal.

Humulin-R + rHuPH20 (Intervention 3): 24 U of rHuPH20 per unit of Humulin-R, injected SC, for up to 2 visits until an appropriate dose was identified.

Humulin-R alone (Intervention 4): a single SC injection of the appropriate identified dose of Humulin-R, delivered before a liquid meal.

Appropriate dose of either Humalog or Humulin-R was that at which blood glucose following a liquid meal was \<160 milligrams per deciliter (mg/dL) for more than 30 minutes during the first 4 hours after injection and never fell below 60 mg/dL.

All dose finding visits and interventions were separated by 3-10 days.

Interventions: intervention 1: Humalog intervention 2: Humulin-R intervention 3: Recombinant human hyaluronidase PH20 (rHuPH20) intervention 4: Liquid meal
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol document: