CompletedNCT05539872Updated Mar 5, 2026Results posted

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 Phase 2/3 interventional study of I004 and NovoLog in Pharmacokinetics and Pharmacodynamics, sponsored by Amphastar Pharmaceuticals, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-05.

Sponsored by Amphastar Pharmaceuticals, Inc. · Phase 2/3, Interventional, and Treatment

Phase: Phase 2/3
Study type: Interventional
Enrollment: 69
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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 studied

Pharmacokinetics
Pharmacodynamics

Keywords

insulin aspart

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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.

Study design

Phase: Phase 2 / Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 69 participants (actual)

Study arms

Experimental
Insulin Aspart, I004
Participants who were dosed with I004
Drug: I004
Active comparator
NovoLog
Participants who were dosed with NovoLog
Drug: NovoLog

Interventions

DrugI004
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
DrugNovoLog
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

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From drug administration to 12 hours post-dose

Secondary outcomes

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 4 to 12 hours post-dose
Time of Maximum Insulin Aspart Serum Concentration, tIAmax
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.
Time frame: Baseline (Time 0) to 12 hours post-dose
Apparent Clearance of Insulin Aspart, CL/F
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.
Time frame: Baseline (Time 0) to 12 hours post-dose
Apparent Volume of Distribution of Insulin Aspart, Vz/F
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.
Time frame: Baseline (Time 0) to 12 hours post-dose
Half-life of Insulin Aspart, t1/2
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.
Time frame: Baseline (Time 0) to 12 hours post-dose
Maximum Serum Human Insulin Concentration, CHImax
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
Time frame: 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 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.
Time frame: 0 to 12 hours post-dose
Time of Maximum Human Insulin Serum Concentration, tHImax
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.
Time frame: 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)
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.
Time frame: 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.
Time frame: 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.
Time frame: From drug administration to 12 hours post-dose
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 1 Hour Post-dose, AUCG(0-1h)
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.
Time frame: From drug administration to 1 hour 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.
Time frame: From drug administration to 2 hours post-dose
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 4 Hours Post-dose, AUCG(0-4h)
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.
Time frame: From drug administration to 4 hours post-dose
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 4 to 12 Hours Post-dose, AUCG(4-12h)
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(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.
Time frame: From 4 hours post-dose 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.
Time frame: From drug administration to 12 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From drug administration to 12 hours post-dose

Other outcomes

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.
Time frame: Baseline (15 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.
Time frame: Baseline (15 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.
Time frame: Baseline (15 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.
Time frame: Baseline (15 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. QT interval was corrected using the Fridericia correction.
Time frame: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose

Results

Posted Mar 5, 2026

Participant flow

Treatment Period 1

Participant flow — Treatment Period 1
Milestone	Treatment T - Treatment R	Treatment R - Treatment T
Started	35	34
Completed	35	34
Not completed	0	0

Washout Period 1 (7-21 Days)

Participant flow — Washout Period 1 (7-21 Days)
Milestone	Treatment T - Treatment R	Treatment R - Treatment T
Started	35	34
Completed	32	30
Not completed	3	4
Withdrew: Adverse event	0	1
Withdrew: Lost to follow-up	1	0
Withdrew: Withdrawal by subject	2	2
Withdrew: Subject unreachable	0	1

Treatment Period 2

Participant flow — Treatment Period 2
Milestone	Treatment T - Treatment R	Treatment R - Treatment T
Started	32	30
Completed	32	28
Not completed	0	2
Withdrew: Adverse event	0	1
Withdrew: Withdrawal by subject	0	1

Outcome measures

PrimaryMaximum 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.

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Geometric mean · pg/mL

Maximum Serum Insulin Aspart Concentration, CIAmax
pg/mL	Insulin Aspart, I004	NovoLog
Maximum Serum Insulin Aspart Concentration, CIAmax	2961.8 ± 32.9	2827.4 ± 31.4

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 104.7 · 90% CI 100.0 to 109.7

PrimaryArea 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.

Time frame:: 0 to 12 hours post-dose
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 12 Hours Post-dose, AUCIA(0-12h)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 12 Hours Post-dose, AUCIA(0-12h)	7215.0 ± 26.0	6976.9 ± 25.1

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 103.3 · 90% CI 101.1 to 105.6

PrimaryMaximum Glucose Infusion Rate, Gmax

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Geometric mean · mg/kg/min

Maximum Glucose Infusion Rate, Gmax
mg/kg/min	Insulin Aspart, I004	NovoLog
Maximum Glucose Infusion Rate, Gmax	10.3 ± 43.3	10.3 ± 39.8

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 99.4 · 90% CI 92.8 to 106.4

PrimaryArea 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.

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 12 Hours Post-dose, AUCG(0-12h)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 12 Hours Post-dose, AUCG(0-12h)	1906.9 ± 37.2	1985.7 ± 39.8

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 96.0 · 90% CI 90.2 to 102.2

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

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.

Time frame:: 0 to infinity (extrapolated; concentrations measured through 12 hours post-dose)
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to Infinity, AUCIA(0-∞)	7374.9 ± 25.5	7202.7 ± 24.4

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 102.7 · 90% CI 100.5 to 104.9

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

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.

Time frame:: 0 to 1 hour post-dose
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 1 Hour Post-dose, AUCIA(0-1h)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 1 Hour Post-dose, AUCIA(0-1h)	1438.9 ± 44.7	1496.6 ± 44.4

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 96.2 · 90% CI 89.7 to 103.0

SecondaryArea 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 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.

Time frame:: 0 to 2 hours post-dose
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 2 Hours Post-dose, AUCIA(0-2h)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 2 Hours Post-dose, AUCIA(0-2h)	3886.9 ± 32.9	3757.0 ± 32.9

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 103.3 · 90% CI 98.6 to 108.3

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

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.

Time frame:: 0 to 4 hours post-dose
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 4 Hours Post-dose, AUCIA(0-4h)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From Time 0 to 4 Hours Post-dose, AUCIA(0-4h)	6478.7 ± 25.9	6204.1 ± 24.6

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 104.3 · 90% CI 101.6 to 107.1

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

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

Time frame:: 4 to 12 hours post-dose
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From 4 to 12 Hours Post-dose, AUCIA(4-12h)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Insulin Aspart Serum Concentration From 4 to 12 Hours Post-dose, AUCIA(4-12h)	567.2 ± 112.9	619.8 ± 119.9

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 97.7 · 90% CI 86.0 to 111.0

SecondaryTime of Maximum Insulin Aspart Serum Concentration, tIAmax

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.

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Median · min

Time of Maximum Insulin Aspart Serum Concentration, tIAmax
min	Insulin Aspart, I004	NovoLog
Time of Maximum Insulin Aspart Serum Concentration, tIAmax	67.5 (25.0 to 180.0)	55.0 (25.0 to 150.0)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 111.8 · 90% CI 101.0 to 123.8

SecondaryApparent Clearance of Insulin Aspart, CL/F

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.

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Geometric mean · L/hr

Apparent Clearance of Insulin Aspart, CL/F
L/hr	Insulin Aspart, I004	NovoLog
Apparent Clearance of Insulin Aspart, CL/F	74.2 ± 25.8	76.3 ± 23.5

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 97.4 · 90% CI 95.3 to 99.4

SecondaryApparent Volume of Distribution of Insulin Aspart, Vz/F

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.

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Geometric mean · L

Apparent Volume of Distribution of Insulin Aspart, Vz/F
L	Insulin Aspart, I004	NovoLog
Apparent Volume of Distribution of Insulin Aspart, Vz/F	96.8 ± 47.3	104.1 ± 48.4

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 93.2 · 90% CI 87.2 to 99.7

SecondaryHalf-life of Insulin Aspart, t1/2

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.

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Median · min

Half-life of Insulin Aspart, t1/2
min	Insulin Aspart, I004	NovoLog
Half-life of Insulin Aspart, t1/2	53.0 (28.0 to 223.8)	60.8 (23.3 to 177.4)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 97.7 · 90% CI 90.8 to 105.2

SecondaryMaximum Serum Human Insulin Concentration, CHImax

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

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Geometric mean · pg/mL

Maximum Serum Human Insulin Concentration, CHImax
pg/mL	Insulin Aspart, I004	NovoLog
Maximum Serum Human Insulin Concentration, CHImax	559.4 ± 53.0	563.8 ± 62.6

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 100.1 · 90% CI 90.6 to 110.7

SecondaryArea 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 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.

Time frame:: 0 to 12 hours post-dose
Reported as:: Geometric mean · pg/mL * hr

Area Under the Curve (AUC) of Human Insulin Serum Concentration From Time 0 to 12 Hours Post-dose, AUCHI(0-12h)
pg/mL * hr	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) of Human Insulin Serum Concentration From Time 0 to 12 Hours Post-dose, AUCHI(0-12h)	2662.7 ± 54.7	2634.8 ± 57.8

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 101.2 · 90% CI 93.8 to 109.1

SecondaryTime of Maximum Human Insulin Serum Concentration, tHImax

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.

Time frame:: Baseline (Time 0) to 12 hours post-dose
Reported as:: Median · min

Time of Maximum Human Insulin Serum Concentration, tHImax
min	Insulin Aspart, I004	NovoLog
Time of Maximum Human Insulin Serum Concentration, tHImax	80.0 (0.0 to 720.0)	105.0 (0.0 to 720.0)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 97.2 · 90% CI 75.4 to 125.5

SecondaryArea 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.

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate Due to Insulin Aspart From Time 0 to 12 Hours Post-dose, AUCGA(0-12h)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate Due to Insulin Aspart From Time 0 to 12 Hours Post-dose, AUCGA(0-12h)	1308.1 ± 42.2	1364.8 ± 39.3

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 95.7 · 90% CI 90.5 to 101.1

SecondaryMaximum Glucose Infusion Rate Due to Insulin Aspart, GAmax

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Geometric mean · mg/kg/min

Maximum Glucose Infusion Rate Due to Insulin Aspart, GAmax
mg/kg/min	Insulin Aspart, I004	NovoLog
Maximum Glucose Infusion Rate Due to Insulin Aspart, GAmax	8.1 ± 47.0	8.3 ± 41.4

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 97.7 · 90% CI 91.6 to 104.3

SecondaryArea 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.

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate (GIR) From Time 0 to the Time of Last Measurable GIR, AUCG(0-last)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate (GIR) From Time 0 to the Time of Last Measurable GIR, AUCG(0-last)	1906.9 ± 37.2	1985.7 ± 39.8

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 96.0 · 90% CI 90.2 to 102.2

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

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.

Time frame:: From drug administration to 1 hour post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 1 Hour Post-dose, AUCG(0-1h)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 1 Hour Post-dose, AUCG(0-1h)	115.8 ± 79.5	123.6 ± 72.0

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 93.6 · 90% CI 84.5 to 103.7

SecondaryArea 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.

Time frame:: From drug administration to 2 hours post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 2 Hours Post-dose, AUCG(0-2h)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 2 Hours Post-dose, AUCG(0-2h)	481.5 ± 51.9	501.9 ± 56.0

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 95.9 · 90% CI 90.5 to 101.5

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

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.

Time frame:: From drug administration to 4 hours post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 4 Hours Post-dose, AUCG(0-4h)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 0 to 4 Hours Post-dose, AUCG(0-4h)	1268.9 ± 43.3	1305.0 ± 44.7

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 97.2 · 90% CI 91.9 to 102.8

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

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(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.

Time frame:: From 4 hours post-dose to 12 hours post-dose
Reported as:: Geometric mean · mg/kg

Area Under the Curve (AUC) for Glucose Infusion Rate From Time 4 to 12 Hours Post-dose, AUCG(4-12h)
mg/kg	Insulin Aspart, I004	NovoLog
Area Under the Curve (AUC) for Glucose Infusion Rate From Time 4 to 12 Hours Post-dose, AUCG(4-12h)	555.9 ± 64.1	589.3 ± 68.2

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 94.2 · 90% CI 84.8 to 104.7

SecondaryLast Measurable Glucose Infusion Rate, Glast

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Geometric mean · mg/kg/min

Last Measurable Glucose Infusion Rate, Glast
mg/kg/min	Insulin Aspart, I004	NovoLog
Last Measurable Glucose Infusion Rate, Glast	0.1 ± 3827.7	0.0 ± 2252.0

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 134.4 · 90% CI 61.6 to 293.0

SecondaryTime of Maximum Glucose Infusion Rate, tGmax

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Median · min

Time of Maximum Glucose Infusion Rate, tGmax
min	Insulin Aspart, I004	NovoLog
Time of Maximum Glucose Infusion Rate, tGmax	160.0 (47.0 to 286.0)	136.0 (43.0 to 265.0)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 110.6 · 90% CI 98.0 to 124.9

SecondaryTime of Glucose Infusion Start, tGonset

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Median · min

Time of Glucose Infusion Start, tGonset
min	Insulin Aspart, I004	NovoLog
Time of Glucose Infusion Start, tGonset	22.0 (1.0 to 40.0)	20.0 (1.0 to 50.0)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 134.3 · 90% CI 101.4 to 178.0

SecondaryTime of Last Measurable Glucose Infusion Rate, tGlast

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Median · min

Time of Last Measurable Glucose Infusion Rate, tGlast
min	Insulin Aspart, I004	NovoLog
Time of Last Measurable Glucose Infusion Rate, tGlast	720.0 (334.0 to 720.0)	712.0 (367.0 to 720.0)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 101.5 · 90% CI 98.2 to 104.9

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

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Median · min

Time to Half of Maximum Glucose Infusion Rate (Gmax) Before Gmax Is Reached, tG50%Early
min	Insulin Aspart, I004	NovoLog
Time to Half of Maximum Glucose Infusion Rate (Gmax) Before Gmax Is Reached, tG50%Early	76.7 (31.4 to 254.7)	71.5 (25.2 to 221.4)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 104.6 · 90% CI 92.0 to 119.0

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

Time frame:: From drug administration to 12 hours post-dose
Reported as:: Median · min

Time to Half of Maximum Glucose Infusion Rate (Gmax) After Gmax Is Reached, tG50%Late
min	Insulin Aspart, I004	NovoLog
Time to Half of Maximum Glucose Infusion Rate (Gmax) After Gmax Is Reached, tG50%Late	211.9 (70.3 to 364.8)	216.2 (66.1 to 361.1)

Statistical analysis

Insulin Aspart, I004 vs NovoLog · Geometric mean ratio: 102.9 · 90% CI 91.5 to 115.7

Other pre-specifiedSystolic 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.

Time frame:: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Reported as:: Mean · mmHg

Systolic Blood Pressure (SBP)
mmHg	Insulin Aspart, I004	NovoLog
Baseline	109 ± 9	109 ± 10
5 minutes post-dose	111 ± 9	109 ± 11
60 minutes post-dose	109 ± 9	108 ± 10
180 minutes post-dose	107 ± 9	107 ± 9
720 minutes post-dose	116 ± 11	113 ± 11

Other pre-specifiedDiastolic 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.

Time frame:: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Reported as:: Mean · mmHg

Diastolic Blood Pressure (DBP)
mmHg	Insulin Aspart, I004	NovoLog
Baseline	70 ± 6	70 ± 6
5 minutes post-dose	70 ± 6	70 ± 7
60 minutes post-dose	68 ± 6	68 ± 6
180 minutes post-dose	67 ± 6	67 ± 5
720 minutes post-dose	71 ± 6	70 ± 7

Other pre-specifiedHeart 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.

Time frame:: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Reported as:: Mean · bpm

Heart Rate (HR)
bpm	Insulin Aspart, I004	NovoLog
Baseline	62 ± 7	64 ± 9
5 minutes post-dose	63 ± 9	62 ± 8
60 minutes post-dose	64 ± 9	66 ± 9
180 minutes post-dose	67 ± 10	66 ± 11
720 minutes post-dose	65 ± 9	66 ± 9

Other pre-specifiedQT 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.

Time frame:: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Reported as:: Mean · ms

QT Interval
ms	Insulin Aspart, I004	NovoLog
Baseline	408 ± 21	409 ± 23
5 minutes post-dose	406 ± 20	407 ± 22
60 minutes post-dose	403 ± 23	399 ± 23
180 minutes post-dose	396 ± 22	397 ± 22
720 minutes post-dose	402 ± 21	401 ± 23

Other pre-specifiedCorrected 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. QT interval was corrected using the Fridericia correction.

Time frame:: Baseline (15 minutes pre-dose), 5 minutes, 60 minutes, 180 minutes, and 720 minutes post-dose
Reported as:: Mean · ms

Corrected QT (QTc-F) Interval
ms	Insulin Aspart, I004	NovoLog
Baseline	409 ± 17	410 ± 18
5 minutes post-dose	411 ± 17	409 ± 20
60 minutes post-dose	408 ± 20	406 ± 20
180 minutes post-dose	407 ± 19	407 ± 19
720 minutes post-dose	412 ± 19	410 ± 19

Adverse events

Collected over From signing of consent until follow-up (approximately 10 weeks). Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Insulin Aspart, I004	0/65 (0%)	0/65 (0%)	7/65 (10.8%)
NovoLog	0/66 (0%)	0/66 (0%)	10/66 (15.2%)

Most frequent other events

Most frequent other events
Event	Insulin Aspart, I004	NovoLog
HeadacheNervous system disorders	4/65	8/66
HypoglycaemiaMetabolism and nutrition disorders	4/65	1/66
CoughRespiratory, thoracic and mediastinal disorders	0/65	2/66

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Intent To Treat Population
Mean	39.6 ± 11.7

Sex: Female, Male
Sex: Female, Male(Participants)	Intent To Treat Population
Female	26
Male	43

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Intent To Treat Population
White	43
Black or African-American	13
Asian	9
Native Hawaiian or Other Pacific Islander	1
American Indian or Alaska Native	0
Other	3

Study locations

1 site

Amphastar Study Site
Chula Vista, California 91911, United States

References and documents

Study documents

Study protocol · Aug 5, 2021
Statistical analysis plan · Sep 8, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided — 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.

Registry details

Key details

Study ID: NCT05539872
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Responsible party: Sponsor
First posted: Sep 14, 2022
Start date: Aug 22, 2022
Primary completion: Jan 29, 2023
Completion: Jan 30, 2023
Results posted: Mar 5, 2026
Last update: Mar 5, 2026

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

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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

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