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Completed

NCT Number: NCT05539872

Comparison of the Pharmacokinetics (PK) and Pharmacodynamics (PD) Biosimilarity of Proposed Biosimilar Rapid-Acting Insulin Aspart (I004) and NovoLog After Single-Dose Subcutaneous Administration to Healthy Volunteers

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 pharmacodynamics (PD) biosimilarity of proposed biosimilar I004 and the US-approved NovoLog.

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Key information

Conditions

Pharmacokinetics Pharmacodynamics

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Amphastar Study Site

Chula Vista, California, 91911, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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 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.

Treatment and study plan

I004

Drug

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 Treatment Period 1 under fasting condition.

Other names: Insulin Aspart, a rapid-acting human insulin analogue

NovoLog

Drug

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 Treatment Period 1 under fasting condition.

Other names: Insulin Aspart, a rapid-acting human insulin analogue

Primary outcomes

  1. Maximum Serum Insulin Aspart Concentration, CIAmax

    Time frame: 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.

  2. Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 12 Hours Post-dose, AUCIA(0-12h)

    Time frame: 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.

  3. Maximum Glucose Infusion Rate, Gmax

    Time frame: 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.

  4. Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 12 Hours Post-dose, AUCG(0-12h)

    Time frame: 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.

Secondary outcomes

  1. Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)

    Time frame: 0 to infinity (extrapolated; concentrations measured through 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-∞) will be calculated from the concentration curves. AUCIA(0-∞) is derived using standard extrapolation beyond the last measurable concentration.

  2. Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 1 Hour Post-dose, AUCIA(0-1h)

    Time frame: 0 to 1 hour 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(0-1h) will be calculated from the concentration curves. Only AUC from 0 to 1 hour (AUCIA(0-1h)) is reported.

  3. Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 2 Hours Post-dose, AUCIA(0-2h)

    Time frame: 0 to 2 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(0-2h) will be calculated from the concentration curves. Only AUC from 0 to 2 hours (AUCIA(0-2h)) is reported.

  4. Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 4 Hours Post-dose, AUCIA(0-4h)

    Time frame: 0 to 4 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(0-4h) will be calculated from the concentration curves. Only AUC from 0 to 4 hours (AUCIA(0-4h)) is reported.

  5. Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From 4 to 12 Hours Post-dose, AUCIA(4-12h)

    Time frame: 4 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(4-12h) will be calculated from the concentration curves. Only AUC from 4 to 12 hours (AUCIA(4-12h)) is reported.

  6. Time of Maximum Insulin Aspart Serum Concentration, tIAmax

    Time frame: 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.

  7. Apparent Clearance of Insulin Aspart, CL/F

    Time frame: 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.

  8. Apparent Volume of Distribution of Insulin Aspart, Vz/F

    Time frame: 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.

  9. Half-life of Insulin Aspart, t1/2

    Time frame: 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.

  10. Maximum Serum Human Insulin Concentration, CHImax

    Time frame: 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 Human Insulin

  11. Area Under the Curve (AUC) of Human Insulin Serum Concentration From Time 0 to 12 Hours Post-dose, AUCHI(0-12h)

    Time frame: 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 Human Insulin. AUCHI(0-12h) will be calculated from the concentration curves. Only AUC from 0 to 12 hours (AUCHI(0-12h)) is reported.

  12. Time of Maximum Human Insulin Serum Concentration, tHImax

    Time frame: 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 Human Insulin.

  13. Area Under the Curve (AUC) for Glucose Infusion Rate Due to Insulin Aspart From Time 0 to 12 Hours Post-dose, AUCGA(0-12h)

    Time frame: 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. 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.

  14. Maximum Glucose Infusion Rate Due to Insulin Aspart, GAmax

    Time frame: 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.

  15. Area Under the Curve (AUC) for Glucose Infusion Rate (GIR) From Time 0 to the Time of Last Measurable GIR, AUCG(0-last)

    Time frame: 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-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.

  16. Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 1 Hour Post-dose, AUCG(0-1h)

    Time frame: From drug administration to 1 hour 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(0-1h) 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.

  17. Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 2 Hours Post-dose, AUCG(0-2h)

    Time frame: From drug administration to 2 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(0-2h) 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.

  18. Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 4 Hours Post-dose, AUCG(0-4h)

    Time frame: From drug administration to 4 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(0-4h) 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.

  19. Area Under the Curve (AUC) for Glucose Infusion Rate From Time 4 to 12 Hours Post-dose, AUCG(4-12h)

    Time frame: From 4 hours post-dose 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(4-12h) 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.

  20. Last Measurable Glucose Infusion Rate, Glast

    Time frame: 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.

  21. Time of Maximum Glucose Infusion Rate, tGmax

    Time frame: 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.

  22. Time of Glucose Infusion Start, tGonset

    Time frame: 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.

  23. Time of Last Measurable Glucose Infusion Rate, tGlast

    Time frame: 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.

  24. Time to Half of Maximum Glucose Infusion Rate (Gmax) Before Gmax Is Reached, tG50%Early

    Time frame: 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.

  25. Time to Half of Maximum Glucose Infusion Rate (Gmax) After Gmax Is Reached, tG50%Late

    Time frame: 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.

Other outcomes

  1. Systolic Blood Pressure (SBP)

    Time frame: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

    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.

  2. Diastolic Blood Pressure (DBP)

    Time frame: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

    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.

  3. Heart Rate (HR)

    Time frame: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

    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.

  4. QT Interval

    Time frame: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

    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.

  5. Corrected QT (QTc-F) Interval

    Time frame: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

    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. QT interval was corrected using the Fridericia correction.

Sponsors and collaborators

Lead sponsor

Amphastar Pharmaceuticals, Inc.

Industry

Registry information

Official study title

Comparison of the Pharmacokinetics (PK) and Pharmacodynamics (PD) Biosimilarity of Proposed Biosimilar 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

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Sep 14, 2022
Registry last updated
Mar 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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