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.

Study Overview

• Status: Recruiting
• Conditions: Pharmacokinetics; Pharmacodynamics; Insulin Aspart
• Intervention / Treatment: Drug: I004; Drug: NovoLog

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Amphastar Pharmaceuticals, Inc.; Phone Number: 909-980-9484; Email: info@amphastar.com

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Recruiting
      • Amphastar Study Site
      • Contact: Amphastar Pharmaceuticals, Inc.; Phone Number: 909-980-9484; Email: info@amphastar.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Aspart, I004; Participants who were dosed with I004	Drug: I004; Drug will be administered via subcutaneous injection into the abdominal wall of the peri-umbilical area with a dose of 0.2 units/kg based on the body weight measured at Day -1 of Treatment Period 1 under fasting condition.; Other Names: Insulin Aspart, a rapid-acting human insulin analogue
Active Comparator: NovoLog; Participants who were dosed with NovoLog	Drug: NovoLog; Drug will be administered via subcutaneous injection into the abdominal wall of the peri-umbilical area with a dose of 0.2 units/kg based on the body weight measured at Day -1 of Treatment Period 1 under fasting condition.; Other Names: Insulin Aspart, a rapid-acting human insulin analogue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 12 Hours Post-dose, AUCIA(0-12h)	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.	0 to 12 hours post-dose
Maximum Glucose Infusion Rate, Gmax	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.	From drug administration to 12 hours post-dose
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 12 Hours Post-dose, AUCG(0-12h)	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.	From drug administration to 12 hours post-dose
Maximum Serum Insulin Aspart Concentration, CIAmax	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	Baseline (Time 0) to 12 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) for Glucose Infusion Rate Due to Insulin Aspart From Time 0 to 12 Hours Post-dose, AUCGA(0-12h)	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. AUCGA(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.	From drug administration to 12 hours post-dose
Maximum Glucose Infusion Rate Due to Insulin Aspart, GAmax	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.	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)	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-last) 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.	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)	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(0-2h) 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.	From drug administration to 2 hours post-dose
Time of Maximum Glucose Infusion Rate, tGmax	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.	From drug administration to 12 hours post-dose
Time of Glucose Infusion Start, tGonset	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.	From drug administration to 12 hours post-dose
Time of Last Measurable Glucose Infusion Rate, tGlast	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.	From drug administration to 12 hours post-dose
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart. AUCIA(0-∞) will be calculated from the concentration curves. AUCIA(0-∞) is derived using standard extrapolation beyond the last measurable concentration.	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)	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart. AUCIA(0-2h) will be calculated from the concentration curves. Only AUC from 0 to 2 hours (AUCIA(0-2h)) is reported.	0 to 2 hours post-dose
Time of Maximum Insulin Aspart Serum Concentration, tIAmax	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart.	Baseline (Time 0) to 12 hours post-dose
Apparent Clearance of Insulin Aspart (CL/F)	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart.	Baseline (Time 0) to 12 hours post-dose
Apparent Volume of Distribution of Insulin Aspart (Vz/F)	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart.	Baseline (Time 0) to 12 hours post-dose
Half-life of Insulin Aspart (t1/2)	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Insulin Aspart.	Baseline (Time 0) to 12 hours post-dose
Maximum Serum Human Insulin Concentration, CHImax	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Human Insulin.	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)	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Human Insulin. AUCHI(0-12h) will be calculated from the concentration curves. Only AUC from 0 to 12 hours (AUCHI(0-12h)) is reported.	Baseline (Time 0) to 12 hours post-dose
Time of Maximum Human Insulin Serum Concentration, tHImax	Pharmacokinetic (PK) blood samples will be collected starting 60 minutes before dose through 12 hours post-dose. Serum will be isolated for analyzing the concentrations of Human Insulin.	Baseline (Time 0) to 12 hours post-dose
Last Measurable Glucose Infusion Rate (Glast)	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.	From drug administration to 12 hours post-dose
Time to Half of Maximum Glucose Infusion Rate (Gmax) Before Gmax Is Reached, tG50%early	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.	From drug administration to 12 hours post-dose
Time to Half of Maximum Glucose Infusion Rate (Gmax) After Gmax Is Reached, tG50%late	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.	From drug administration to 12 hours post-dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure (SBP)	Participant vital signs were measured in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.	Baseline (30 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Diastolic Blood Pressure (DBP)	Participant vital signs were measured in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.	Baseline (30 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Heart Rate (HR)	Participant vital signs were measured in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.	Baseline (30 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
QT Interval	A standard 12-lead electrocardiogram (ECG) was recorded in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.	Baseline (30 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Corrected QT (QTc-F) Interval	A standard 12-lead electrocardiogram (ECG) was recorded in a supine position, after a 5-minute resting period, before drug administration (baseline) and at specified time points after dosing.	Baseline (30 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

Collaborators and Investigators

• Sponsor: Amphastar Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Insulin, Short-Acting; Insulin Aspart
• Other Study ID Numbers: API-I004-CL-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Access to patient level data and supporting clinical documents may be requested by qualified researchers. Requests will be reviewed on the basis of scientific merit. Patient data will be de-identified to protect the privacy of trial patients in line with applicable laws and regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No