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

NCT05539872 | Completed Phase 2 Results FDA Drug

• 1 other identifier: API-I004-CL-B
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pharmacokinetics; Pharmacodynamics

Keywords

insulin aspart

Outcome Measures

Primary Outcomes (4)

• 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

• 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

Secondary Outcomes (25)

• 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 1 Hour Post-dose, AUCIA(0-1h)

  0 to 1 hour 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

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

  0 to 4 hours post-dose

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

  4 to 12 hours post-dose

Other Outcomes (5)

• Systolic Blood Pressure (SBP)

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

• Diastolic Blood Pressure (DBP)

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

• Heart Rate (HR)

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

Study Arms (2)

Insulin Aspart, I004

EXPERIMENTAL

Participants who were dosed with I004

Drug: I004

NovoLog

ACTIVE COMPARATOR

Participants who were dosed with NovoLog

Drug: NovoLog

Interventions

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.

Also known as: Insulin Aspart, a rapid-acting human insulin analogue

Insulin Aspart, I004

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.

Also known as: Insulin Aspart, a rapid-acting human insulin analogue

NovoLog

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (1)

Amphastar Study Site

Chula Vista, California, 91911, United States

Location

MeSH Terms

Interventions

Insulin Aspart

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Amphastar Pharmaceuticals, Inc.
• Organization: Amphastar Pharmaceuticals, Inc.

info@amphastar.com

(909) 980-9484

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 14, 2022
• Study Start: August 22, 2022
• Primary Completion: January 29, 2023
• Study Completion: January 30, 2023
• Last Updated: March 5, 2026
• Results First Posted: March 5, 2026

Record last verified: 2026-02

Locations

US (1)