Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Humalog · 3 trials · 3 indications
Postprandial glucose (PPG) values in participants receiving Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), or Humulin-R + rHuPH20 following a liquid meal are reported. Blood samples were collected at 30, 20, 10, and within 5 minutes before and at 3, 6, 9, 12, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150, 180, 210, 240, 300, 360, 420, and 480 minutes after injection of each study drug. Least square mean difference was calculated and tested using repeated measures analysis of variance with fixed effect for treatment.
AUC was derived as the area under the serum insulin concentration profile from 0 to time "t." Samples were taken 30, 20, and 10 minutes (mins) prior to treatment; every 3 mins from mins 0 through 15; and at 20, 30, 45, and 60 mins postdose.
Time to maximum serum insulin concentration (tmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Maximum serum insulin concentration (Cmax) values for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Area under the serum concentration-time curve from time zero to the time required to reach endogenous plasma glucose levels (AUC\[0-t'\]) for participants who received Humalog or Humulin-R with or without recombinant human hyaluronidase PH20 (rHuPH20) were measured from 3 milliliter (mL) blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Area under the concentration-time curve from time 0 to time to reach maximum concentration (tmax) for serum insulin (Humalog or Humulin-R) with recombinant human hyaluronidase (rHuPH20) (AUC\[0-tmaxPH20\]) for participants who received Humalog or Humulin-R and with rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment and every 3 min from min 0 through 48 for Stage 1 and, and every 3 min from min 0 through 68 for Stage 2 during the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
Relative bioavailability was determined by dividing the baseline-corrected geometric mean of the area under the curve (AUC) for insulin (ins) (Humalog or Humulin-R) with recombinant human hyaluronidase PH20 (rHuPH20) by the baseline-corrected geometric mean of the AUC for insulin alone (AUC\[insulin+rHuPH20\]/AUC\[insulin\]). Bioavailability values for participants who received Humalog or Humulin-R and rHuPH20 were measured from blood samples obtained during a euglycemic clamp procedure. Samples were taken 10 and 1 minute (min) prior to treatment, every 3 min from min 0 through 60, every 15 min from min 60 through 180, and every 60 min from min 180 through 360 throughout the clamp procedure. Means were calculated using analysis of variance with effects of participant, sequence within participant, treatment, and period.
| Arm | Type | Description |
|---|---|---|
| Humalog, Then Humalog + rHuPH20, Then Humulin-R + rHuPH20 | ACTIVE_COMPARATOR | A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout period), followed by a SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3 to 14 day washout period. |
| Humalog, Then Humulin-R + rHuPH20, Then Humalog + rHuPH20 | ACTIVE_COMPARATOR | A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog alone for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 nanograms/kilogram (ng/kg) recombinant human hyaluronidase PH20 (rHuPH20). The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period. |
| Humalog + rHuPH20, Then Humalog, Then Humulin-R + rHuPH20 | ACTIVE_COMPARATOR | A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase PH20(rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humulin-R + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period. |
| Humalog + rHuPH20, Then Humulin-R + rHuPH20, Then Humalog | ACTIVE_COMPARATOR | A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humalog + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humalog + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humulin-R + rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog following a 3- to 14-day washout period. |
| Humulin-R + rHuPH20, Then Humalog, Then Humalog + rHuPH20 | ACTIVE_COMPARATOR | A subcutaneous (SC) injection of up to 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog alone. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20 following a 3- to 14-day washout period. |
| Humulin-R + rHuPH20, Then Humalog + rHuPH20, Then Humalog | ACTIVE_COMPARATOR | A subcutaneous (SC) injection of 0.3- to 0.5-units per kilogram (U/kg) of Humulin-R + 3.75 nanograms per kilogram (ng/kg) of recombinant human hyaluronidase PH20 (rHuPH20) for up to 3 dose-finding (DF) visits (each visit separated by a 3- to 14-day washout), followed by a single SC injection of the appropriate dose of Humulin-R + rHuPH20. After a 3- to 14-day washout period, the DF process and injection of appropriate dose was repeated with 0.3- to 0.5-U/kg Humalog + 3.75 ng/kg rHuPH20. The DF process and injection of appropriate dose was then repeated with 0.3- to 0.5-U/kg Humalog alone following a 3- to 14-day washout period. |
| First Humalog+PH20, then Humalog, Humulin-R+PH20, Humulin-R | EXPERIMENTAL | 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. |
| Humalog first, then Humalog + rHuPH20 | ACTIVE_COMPARATOR | Humalog first, then Humalog + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humalog on Day 1 of the study, followed by a single SC injection of 20 U Humalog + 300 U rHuPH20 after a washout period of at least 6 days |
| Humalog + rHuPH20 first, then Humalog | ACTIVE_COMPARATOR | Humalog + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humalog A single subcutaneous (SC) injection of 20 units (U) Humalog + 300 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humalog after a washout period of at least 6 days |
| Humulin-R first, then Humulin-R + rHuPH20 | ACTIVE_COMPARATOR | Humulin-R (recombinant human insulin) first, then Humulin-R + recombinant human hyaluronidase PH20 (rHuPH20) A single subcutaneous (SC) injection of 20 units (U) Humulin-R on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R + 240 U rHuPH20 after a washout period of at least 6 days |
| Humulin-R + rHuPH20 first, then Humulin-R | ACTIVE_COMPARATOR | Humulin-R (recombinant human insulin) + recombinant human hyaluronidase PH20 (rHuPH20) first, then Humulin-R A single subcutaneous (SC) injection of 20 units (U) Humulin-R + 240 U rHuPH20 on Day 1 of the study, followed by a single SC injection of 20 U Humulin-R after a washout period of at least 6 days |
| Name | Type | Description |
|---|---|---|
| Humalog | DRUG | - |
| Humulin-R | DRUG | - |
| Recombinant human hyaluronidase PH20 (rHuPH20) | DRUG | - |
| Liquid meal | OTHER | - |
Inclusion Criteria: * Male or female of age 18 to 70 years, inclusive * Participants with Type 2 diabetes mellitus (T2DM) per World Health Organization criteria treated with basal and/or bolus insulin for ≥12 months. * Body mass index (BMI) between 18 to 45 kilograms per square meter (kg/m\^2), inc...
Humalog is an insulin product used for the treatment of diabetes mellitus, including Type 1 and Type 2 diabetes. It is being studied in combination with recombinant human hyaluronidase (rHuPH20) to potentially improve the absorption and action of the insulin.
Humalog is being developed by Halozyme Therapeutics, Inc., which trades under the ticker HALO. The company is conducting clinical trials to evaluate the use of Humalog with rHuPH20 for diabetes treatment.
Humalog is in Phase 1 clinical development for diabetes mellitus. The Phase 1 trial is completed, and it was a randomized, double-blind, active-controlled study. Humalog is investigational and not yet approved for the studied combination.
Humalog has been studied in clinical trials including NCT00705536, a Phase 1 pharmacokinetic and pharmacodynamic study in healthy volunteers, and NCT00774800 and NCT00916357, which are Phase 2 studies in patients with Type 1 and Type 2 diabetes, respectively.
Humalog is a brand name for insulin lispro. In clinical trials, it is being studied with and without recombinant human hyaluronidase (rHuPH20) to evaluate its pharmacokinetics and pharmacodynamics in diabetes.