Comparison of the Pharmacokinetics (PK) and Pharmacodynamics (PD) Biosimilarity of Proposed Biosimilar/Interchangeable Rapid-Acting Insulin Aspart (I004) and NovoLog® After Single-Dose Subcutaneous Administration to Healthy Volunteers: A Single-Center Randomized, Double-Blinded, Two-Treatment, Two-Period, Two-Sequence, Crossover, Hyperinsulinemia-Euglycemic Clamp Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Maximum Serum Insulin Aspart Concentration, CIAmax
研究概览
简要总结
This study is a randomized, double-blinded, two-treatment, two-period, two-sequence crossover pivotal Biosimilar study. The purpose of this study is to establish pharmacokinetic (PK) and pharmacodynamic (PD) biosimilarity of proposed biosimilar I004 and the US-approved NovoLog.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Upon review, agree to participate and sign informed consent.
- •Healthy male and female subjects ≥ 18 to ≤ 65 years of age.
- •Body mass index (BMI) ≥ 18.5 to ≤ 29.9 kg/m2
- •Weight ≥ 50 kg.
- •Fasting plasma glucose of < 100 mg/dL (5.5 mmol/L) measured with YSI at site; one repeat test is allowed.
- •HbA1c < 5.7%.
- •Non-smoker for ≥ 3 months prior to Screening.
- •Female candidates must be > 1 year post-menopausal, surgically sterile, or practicing a clinically acceptable form of birth control and confirmed by negative serum pregnancy test at Screening.
排除标准
- •History of diabetes mellitus.
- •Resting blood pressure (BP) > 140/90 mmHg or < 90/60 mmHg. Subjects BP may be re-checked.
- •Participation in an investigational drug/device study within 30 days or 5 half-lives within the last dose of any study drug, whichever is longer.
- •History of any serious adverse reaction or hypersensitivity to any of the investigational product components.
- •Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders or abnormalities, or other major systemic disease that, according to the investigator, would unduly risk the subject's safety or may impact the conduct of the study.
- •Subject shows evidence of significant active neuropsychiatric disease, including taking prescription medication for such diseases (including anti-depressant/anti-anxiety medication).
- •Presence of clinically significant physical, laboratory, or ECG findings at Screening that, in the opinion of the Investigator, may interfere with any aspect of study conduct or interpretation of results, or may present a safety issue to that particular subject (laboratory results may be re-checked once on a separate day per Investigator discretion).
- •Long QT syndrome or family history of long QT syndrome or corrected QT interval (QTcF) > 450 ms in men, > 470 ms in women at Screening.
- •Liver function test results of AST and/or ALT ≥ 2.5 upper normal limit (ULN)
- •Subject has a history of syncope.
- •History of any major surgery within 6 months.
- •History of any active infection, other than mild viral illness within 30 days prior to dosing.
- •History of blood clots (e.g., deep vein thrombosis or embolism) or a frequent appearance in 1st degree relatives as judged by the Investigator.
- •Known history or positive test of hepatitis B surface antigen (HBsAG), hepatitis C antibody (HCV Ab), or human immunodeficiency virus type 1 (HIV-1) or 2 (HIV-2) antibody.
- •History of systemic glucocorticoid use within 3 months before screening.
- •History of alcohol abuse as judged by the Investigator within approximately 1 year. Average weekly alcohol intake > 21 units/week (males) and > 14 units/week (females) or are unwilling to stop alcohol consumption from 24 hours prior to each dosing until discharged from the clinical research unit (CRU). Positive alcohol test at Screening. (One unit of alcohol equals about 250 mL of beer or lager, one glass of wine, or 20 mL of spirits).
- •History of illicit drug abuse, including marijuana, within approximately 1 year or evidence of current use as judged by the Investigator. Positive drug test at Screening.
- •Donation or loss of > 500 mL of blood within 56 days.
- •Chronic use of over-the-counter or prescription medication within 7 or 14 days prior to dosing (apart from vitamin/mineral supplements, occasional paracetamol, or birth control methods [Desogestrel is not allowed]).
- •Unable to comply with the safety monitoring requirements of this clinical study or is considered by the investigator to be an unsuitable candidate for the study.
- •Women who are pregnant of breast-feeding.
结局指标
主要结局
Maximum Serum Insulin Aspart Concentration, CIAmax
时间窗: Baseline (Time 0) to 12 hours post-dose
Pharmacokinetic (PK) blood samples will be collected from 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 12 Hours Post-dose, AUCIA(0-12h)
时间窗: 0 to 12 hours post-dose
Pharmacokinetic (PK) blood samples will be collected from 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart. AUCIA(0-12h) will be calculated from the concentration curves. Only AUC from 0 to 12 hours (AUCIA(0-12h)) is reported.
Maximum Glucose Infusion Rate, Gmax
时间窗: From drug administration to 12 hours post-dose
Participants will undergo a euglycemic clamp, where blood glucose concentration will be held at a constant target level by adjusting exogenous glucose infusion rate (GIR) following drug administration. GIR will be recorded for the duration of the euglycemic clamp and used to evaluate the Pharmacodynamic (PD) response.
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 12 Hours Post-dose, AUCG(0-12h)
时间窗: From drug administration to 12 hours post-dose
Participants will undergo a euglycemic clamp, where blood glucose concentration will be held at a constant target level by adjusting exogenous glucose infusion rate (GIR) following drug administration. GIR will be recorded for the duration of the euglycemic clamp and used to evaluate the Pharmacodynamic (PD) response. AUCG(0-12h) will be calculated from the glucose infusion rate curves. Because GIR is recorded in mg/kg/min, the area under the GIR-time curve has units mg/kg.
次要结局
- Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)(0 to infinity (extrapolated; concentrations measured through 12 hours post-dose))
- Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 2 Hours Post-dose, AUCIA(0-2h)(0 to 2 hours post-dose)
- Time of Maximum Insulin Aspart Serum Concentration, tIAmax(Baseline (Time 0) to 12 hours post-dose)
- Apparent Clearance of Insulin Aspart (CL/F)(Baseline (Time 0) to 12 hours post-dose)
- Apparent Volume of Distribution of Insulin Aspart (Vz/F)(Baseline (Time 0) to 12 hours post-dose)
- Half-life of Insulin Aspart (t1/2)(Baseline (Time 0) to 12 hours post-dose)
- Maximum Serum Human Insulin Concentration, CHImax(Baseline (Time 0) to 12 hours post-dose)
- Area Under the Curve (AUC) of Human Insulin Serum Concentration From Time 0 to 12 hours post-dose, AUCHI(0-12h)(Baseline (Time 0) to 12 hours post-dose)
- Time of Maximum Human Insulin Serum Concentration, tHImax(Baseline (Time 0) to 12 hours post-dose)
- Area Under the Curve (AUC) for Glucose Infusion Rate Due to Insulin Aspart From Time 0 to 12 Hours Post-dose, AUCGA(0-12h)(From drug administration to 12 hours post-dose)
- Maximum Glucose Infusion Rate Due to Insulin Aspart, GAmax(From drug administration to 12 hours post-dose)
- Area Under the Curve (AUC) for Glucose Infusion Rate (GIR) From Time 0 to the Time of Last Measurable GIR, AUCG(0-last)(From drug administration to 12 hours post-dose)
- Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 2 Hours Post-dose, AUCG(0-2h)(From drug administration to 2 hours post-dose)
- Last Measurable Glucose Infusion Rate (Glast)(From drug administration to 12 hours post-dose)
- Time of Maximum Glucose Infusion Rate, tGmax(From drug administration to 12 hours post-dose)
- Time of Glucose Infusion Start, tGonset(From drug administration to 12 hours post-dose)
- Time of Last Measurable Glucose Infusion Rate, tGlast(From drug administration to 12 hours post-dose)
- Time to Half of Maximum Glucose Infusion Rate (Gmax) Before Gmax Is Reached, tG50%early(From drug administration to 12 hours post-dose)
- Time to Half of Maximum Glucose Infusion Rate (Gmax) After Gmax Is Reached, tG50%late(From drug administration to 12 hours post-dose)