Phase 1
Completed N=26
Pharmacokinetic (PK), Pharmacodynamic (PD), and Safety Study of Subcutaneously Administered Humalog® With and Without Recombinant Human Hyaluronidase (rHuPH20)and Humulin-R® With and Without rHuPH20
Source: ClinicalTrials.gov NCT00705536 ↗Enrolled (actual)
26
Serious AEs
0.0%
Results posted
Jul 2014
Primary outcomePrimary: Time to Maximum Serum Insulin Concentration (Tmax) — 97.5; 48.0; 163; 67.8 Minutes — p=0.0006
Summary
The purpose of the study is to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of Humalog (insulin lispro) or Humulin-R (recombinant human insulin) when administered as a single subcutaneous (SC) injection of 20 units (U) with or without coadministration of recombinant human hyaluronidase PH20 (rHuPH20).
The study hypothesizes that the time required to reach maximum insulin concentration (tmax) when insulin is administered with rHuPH20 will be comparable or shorter than the time required without rHuPH20.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Maximum Serum Insulin Concentration (Tmax) |
97.5; 48.0; 163; 67.8 | 0.0006 sig |
| PRIMARY Maximum Serum Insulin Concentration (Cmax) |
680; 1290; 390; 944 | 0.0003 sig |
| PRIMARY Area Under the Serum Concentration-Time Curve From Time Zero to the Time Required to Reach Endogenous Plasma Glucose Levels (AUC[0-t']) |
116000; 133000; 91400; 137000 | 0.0401 sig |
| PRIMARY Area Under the Concentration-Time Curve From Time 0 to Time to Reach Maximum Concentration (Tmax) for Serum Insulin With Recombinant Human Hyaluronidase PH20 (rHuPH20) (AUC[0-tmaxPH20]) |
9530; 27900; 8780; 34800 | <0.0001 sig |
| PRIMARY Relative Bioavailability (Area Under the Curve [AUC] for Insulin + Recombinant Human Hyaluronidase [rHuPH20] / AUC for Insulin Alone) |
1.18; 1.57 | — |
| SECONDARY Time to Maximum Glucose Infusion Rate (tGIR[Max]) |
193; 114; 253; 165 | 0.0059 sig |
| SECONDARY Time to Early Half-Maximal Effect for Glucose Infusion Rate (tGIR[early50%]) |
72.3; 43.8; 104; 47.4 | 0.0002 sig |
| SECONDARY Time to Late Half-Maximal Effect for Glucose Infusion Rate (tGIR[late50%]) |
324; 275; 282 | 0.3019 |
| SECONDARY Maximum Glucose Infusion Rate (GIR[Max]) |
8.11; 8.57; 7.82; 10.5 | 0.5589 |
| SECONDARY Area Under the Glucose Infusion Rate Curve From 0 to 60 Minutes After Injection (AUC[GIR{0-60}]) |
82.8; 167; 74.3; 180 | — |
| SECONDARY Area Under the Glucose Infusion Rate Curve From 0 to 120 Minutes After Injection (AUC[GIR{0-120}]) |
393; 597; 281; 637 | — |
| SECONDARY Area Under the Glucose Infusion Rate Curve From 0 to 180 Minutes After Injection (AUC[GIR{0-180}]) |
801; 1040; 604; 1150 | — |
| SECONDARY Area Under the Glucose Infusion Rate Curve From 0 to 240 Minutes After Injection (AUC[GIR{0-240}]) |
1240; 1430; 1010; 1630 | — |
| SECONDARY Area Under the Glucose Infusion Rate Curve From 0 to 360 Minutes After Injection (AUC[GIR{0-360}]) |
1940; 1930; 1860; 2260 | — |
Eligibility Criteria
Inclusion Criteria
- Healthy male participants aged 18 to 55 years.
- Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m^2) and total body weight >70 kilograms (kg) (154 pounds [lb]).
- Willingness and ability to comply with the protocol.
- Vital signs within the normal range.
- Within 7 days before the first injection, metabolic panel results and complete blood count (CBC) within the laboratory normal reference range.
- Fasting plasma glucose within the normal range of 90 to 110 milligrams per deciliter (mg/dL) on the morning of the glucose clamp.
- Agreement not to father a child or donate sperm and to use effective contraception during the study and for at least 30 days after study completion.
- Willingness and ability to sign an informed consent form.
Exclusion Criteria
- Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to include history of seizures) or allergic disease, or history of hypoglycemic episodes.
- Known history of diabetes mellitus.
- Prior exposure to any insulin or insulin analogs.
- Known allergy to hyaluronidase or any other ingredient in HYLENEX.
- Known allergy to bee or vespid venom.
- Positive urine drug screen results.
- Positive human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B, or hepatitis C antibody test result.
- Any history or evidence of alcohol or drug abuse.
- History or evidence of use of any tobacco- or nicotine-containing product within 6 months of screening, or screening urine nicotine concentration >50 nanograms per milliliter (ng/mL).
- Use of prescription or nonprescription drugs within 7 days or 5 half-lives, whichever was shorter, except acetaminophen at doses of less than or equal to 1 gram per day (g/day).
- Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.
- Failure to limit alcohol consumption and refrain from exercise within 48 hours before each injection.
- Known clinically significant intercurrent illness or other major systemic disease that would unduly risk the participant's safety or interfere with the interpretation of results.
- Participation in a study of any investigational drug or device 30 days before enrollment in this study.
- Unfitness for the study, in the investigator's opinion.
Data sourced from ClinicalTrials.gov (NCT00705536). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.