Phase 1, Randomized, Double-Blind, Pharmacokinetic and Glucodynamic 6-Way Crossover Study of SC Administered Insulin Lispro With Recombinant Human Hyaluronidase (rHuPH20) and Regular Human Insulin With Recombinant Human Hyaluronidase (rHuPH20) Compared to Insulin Lispro Alone in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T])
研究概览
简要总结
Insulin lispro and regular human insulin are Food and Drug Administration (FDA)-approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase (rHuPH20) is approved by the FDA as an aid to the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both insulin lispro and regular human insulin 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.
详细描述
The purpose of this study is to compare the pharmacokinetics (absorption, distribution, breakdown and elimination) of regular human insulin + recombinant human hyaluronidase (rHuPH20) versus insulin lispro alone, and to compare the pharmacokinetics of insulin lispro + rHuPH20 versus insulin lispro alone. The effects of regular human insulin + rHuPH20, insulin lispro + rHuPH20, and insulin lispro alone on the body will be evaluated by blood glucose measurements and by calculating the rate at which a glucose solution is infused to maintain blood glucose within a certain range. The safety and tolerability of insulin lispro with and without rHuPH20 and regular human insulin with rHuPH20 will be studied. The study drugs will be administered by subcutaneous (under the skin) injection.
研究设计
- 研究类型
- Interventional
- 干预模型
- Crossover
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities.)
- •Body mass index (BMI) between 18-27 kilograms per meter squared (kg/m^2), inclusive.
- •Total body weight >65 kilograms (kg) (143 pounds [lb]) for men and >46 kg (101 lb) for women.
- •Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
- •Vital signs (blood pressure, pulse rate, body temperature) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS).
- •Fasting blood glucose level <100 milligrams per deciliter (mg/dL) at screening.
- •A negative serum pregnancy test (if female of childbearing potential).
- •Female participants of childbearing potential must agree to be practicing effective birth control or abstinence currently and agree to continue to do so for the duration of their time on study.
- •Signed, written Institutional Review Board (IRB)-approved informed consent.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, oncologic, or neurologic (to include history of seizures) disease; hypoglycemic episodes; intercurrent illness (such as influenza); or allergic disease (including severe drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
- •As judged by the Investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary.)
- •Known history of diabetes mellitus (type 1 or type 2) or gestational diabetes.
- •Known allergy to hyaluronidase or any other ingredient in the study drug.
- •Positive human immunodeficiency virus (HIV 1) antibody test, hepatitis B (anti-hepatitis B surface antigen [anti-HBsAg]) or hepatitis C (anti-hepatitis C virus [anti-HCV]) antibody test.
- •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 and a screening qualitative urine nicotine test.
- •Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action or glucose utilization.
- •Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.
- •Participation in a study of any investigational drug or device 30 days before enrollment in this study.
- •The participant is unfit for the study in the opinion of the Investigator.
- •Women who are pregnant or breast-feeding.
研究组 & 干预措施
Insulin Lispro, Regular Human Insulin, rHuPH20
All participants were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C).
Intervention A: a single, subcutaneous (SC) injection of 0.15 units per kilogram (U/kg) insulin lispro with 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase (rHuPH20)
Intervention B: a single, SC injection of 0.15 U/kg regular human insulin (RHI) with 3.75 ng/kg rHuPH20
Intervention C: a single, SC injection of 0.15 U/kg insulin lispro alone
There was a washout period of 3 to 14 days between interventions.
The treatment sequence (ABC, ACB, BAC, BCA, CAB, or CBA) was repeated once so that each participant received up to 6 injections.
干预措施: Insulin Lispro (Drug)
Insulin Lispro, Regular Human Insulin, rHuPH20
All participants were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C).
Intervention A: a single, subcutaneous (SC) injection of 0.15 units per kilogram (U/kg) insulin lispro with 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase (rHuPH20)
Intervention B: a single, SC injection of 0.15 U/kg regular human insulin (RHI) with 3.75 ng/kg rHuPH20
Intervention C: a single, SC injection of 0.15 U/kg insulin lispro alone
There was a washout period of 3 to 14 days between interventions.
The treatment sequence (ABC, ACB, BAC, BCA, CAB, or CBA) was repeated once so that each participant received up to 6 injections.
干预措施: Regular Human Insulin (Drug)
Insulin Lispro, Regular Human Insulin, rHuPH20
All participants were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C).
Intervention A: a single, subcutaneous (SC) injection of 0.15 units per kilogram (U/kg) insulin lispro with 3.75 nanograms per kilogram (ng/kg) recombinant human hyaluronidase (rHuPH20)
Intervention B: a single, SC injection of 0.15 U/kg regular human insulin (RHI) with 3.75 ng/kg rHuPH20
Intervention C: a single, SC injection of 0.15 U/kg insulin lispro alone
There was a washout period of 3 to 14 days between interventions.
The treatment sequence (ABC, ACB, BAC, BCA, CAB, or CBA) was repeated once so that each participant received up to 6 injections.
干预措施: rHuPH20 (Drug)
结局指标
主要结局
Intra-participant Variability in Percent of Total Area Under the Plasma Insulin Concentration-Versus-Time Curve Attained by Time T (%AUC[0-T])
时间窗: predose up to 30 minutes postdose
Blood samples were taken 30, 20, 10 minutes (mins) prior to each injection; every 3 mins (from 0 to 15 mins); and every 5 mins (from 15 to 30 mins) after each injection. The percent coefficient of variation (CV%) was calculated as 100\*(standard deviation/mean). The intra-participant CV% was calculated directly from the 2 replications of each treatment. The CV% for percentage of total AUC is reported from 0 to 30 minutes.
次要结局
- Time to Early and Late 50% Maximum Serum Insulin Concentration (t[50%Max])(predose up to 480 minutes postdose)
- Peak Serum Insulin Concentration (Cmax)(predose up to 480 minutes postdose)
- Time to Percentage of Total Glucose Infused(predose up to 480 minutes postdose)
- Number of Treatment Emergent Adverse Events (TEAEs) Related to Study Drug(first dose through 7 to 10 days after last dose)
- Percentage of Total Glucose Infused(predose up to 240 minutes postdose)