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

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

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.