Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS(A), US-NovoLog®, and EU-NovoRapid®

A Single-center, Single-dose, Double-blind, Randomized, Three-period, Three-treatment, Six-sequence, Crossover Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS(A), US-NovoLog®, and EU-NovoRapid® Using the Euglycemic Clamp Technique in Healthy Male Adult Volunteers

Single-dose, double-blind, randomized, three-period, three-treatment, six-sequence, crossover study to demonstrate pharmacokinetic and pharmacodynamic similarity between NKF-INS(A), US-NovoLog®, and EU-NovoRapid®

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: NKF-INS(A); Drug: EU-NovoRapid®; Drug: US-NovoLog®

Detailed Description

A single-center, single-dose, double-blind, randomized, three-period, three-treatment, six-sequence, crossover study to demonstrate pharmacokinetic and pharmacodynamic similarity between NKF-INS(A), US-NovoLog®, and EU-NovoRapid® using the euglycemic clamp technique in healthy male adult volunteers

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Bloemfontein, South Africa, 9301
    • Xentria Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed and dated informed consent obtained before any trial-related activities. Trial-related activities are any procedures that would not have been done during normal management of the participant
2. Healthy male participants
3. Age between 18 and 50 years, both inclusive
4. Body Mass Index between 18.5 and 29.0 kg/m2, both inclusive
5. Body weight ≥ 50 kg
6. Fasting plasma glucose concentration ≤ 5.5 mmol/L at screening
7. Considered generally healthy upon completion of medical history, physical examination, vital signs, electrocardiogram (ECG), and analysis of laboratory safety variables, as judged by the Investigator
8. Willing and able to comply with scheduled visits, treatment plan, clinical laboratory tests, and other study procedures including lifestyle considerations.
9. Participants must agree to use condoms during sexual intercourse. Additionally, female partners of male participants should use highly effective contraception. All contraceptive measures apply from screening until 90 days after study
10. Have competence in speaking, writing, and comprehending the local language(s) where the study is conducted.

Exclusion Criteria:

1. Positive for human insulin antibodies at Screening
2. Are currently enrolled in or have discontinued within 3 months or 5 half-lives (whichever is longer) of any investigational drug or device or are concurrently enrolled in any other type of medical research study and judged not to be scientifically or medically compatible with this study.
3. Have known allergies to insulin, its excipients, or related drugs or have history of relevant allergic reactions of any origin.
4. History of diabetes mellitus; episodes of hypoglycemia in the anamnesis; any history of insulin use for treatment purposes.
5. Have known allergies to insulin, its excipients, or related drugs or have history of relevant allergic reactions of any origin.
6. Have clinically relevant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study drug; or of interfering with the interpretation of data.
7. Increased risk of thrombosis, e.g., individuals with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator.
8. Clinically significant abnormal ECG at screening.
9. Glycemia level ≥140.4 mg/dL 2 hours after the glucose load.
10. Show evidence of significant active neuropsychiatric disease.
11. Positive urine drug test at screening and/or evidence of current use of known drugs of abuse or have a history of use within the past year.
12. Show evidence of an acute infection with fever or infectious disease at the time of enrollment.
13. Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies at screening.
14. Have positive test results for hepatitis B surface antigen (HBsAg), immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc), or hepatitis C virus (HCV) antibodies at screening.
15. Intend to use over-the-counter medication within 7 days or prescription medication within 14 days prior to dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement).
16. Have donated blood or had a blood loss of 450 mL 3 months prior to study enrollment.
17. Have an average weekly alcohol intake that exceeds 21 units per week or is unwilling to stop alcohol consumption from 48 hours prior to each dosing until being discharged from the CRU.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKF-INS(A); Single subcutaneous dose administration over three treatment periods	Drug: NKF-INS(A); Single subcutaneous dose of 0.3 U/kg administration over three treatment periods
Active Comparator: EU-NovoRapid®; Single subcutaneous dose administration over three treatment periods	Drug: EU-NovoRapid®; Single subcutaneous dose of 0.3 U/kg administration over three treatment periods
Active Comparator: US-NovoLog®; Single subcutaneous dose administration over three treatment periods	Drug: US-NovoLog®; Single subcutaneous dose of 0.3 U/kg administration over three treatment periods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspart Concentration-time Curve From 0 to 12 Hours Area Under the Insulin Aspart Concentration-Time Curve (AUC0-t).	Compared the Pharmacokinetics (PK) of NKF-INS(A) to United States (US)-approved and European Union (EU)-authorized insulin aspart demonstrating PK similarity for insulin aspart.	Day 1 for 12 Hours
Maximum Observed Insulin Aspart Concentration Maximum Observed Insulin Aspart Concentration (Cmax)	Compared the Pharmacokinetic (PK) of NKF-INS(A) to United States (US)-approved and European Union (EU)-authorized insulin aspart demonstrating PK similarity for insulin aspart.	Day 1 for 12 Hours
Area Under the GIR-time Curve From 0 to 12 Hours (AUCGIR0-t).	Compared the Pharmacodynamic (PD) of NKF-INS(A) to United States (US)-approved and European Union (EU)-authorized insulin aspart injection by examining Glucose Infusion Rate (GIR) profiles after a single Subcutaneous (SC) dose.	Day 1 for 12 Hours
Maximum GIR (GIRmax) of Glucose	Compared the Pharmacodynamic (PD) of NKF-INS(A) to United States (US)-approved and European Union (EU)-authorized insulin aspart injection by examining Glucose Infusion Rate (GIR) profiles after a single Subcutaneous (SC) dose.	Day 1 for 12 Hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameters for Serum Insulin Aspart Concentrations: Area Under the Insulin Aspart Concentration-Time Curve (AUC0)-4h, AUC0-6h, AUC0-12h, AUC0-∞	Evaluated additional Pharmacokinetic (PK) parameters of NKF-INS(A) compared to United Stated (US)-approved and European Union (EU)-authorized insulin aspart.	Day 1 for 12 Hours
Time to Half-maximum Before Maximum Observed Insulin Aspart Concentration Time to Half-Maximum Before Maximum Observed Insulin Aspart Concentration (t50%-Early)	Evaluated Additional Pharmacokinetic (PK) Parameters of NKF-INS(A) Compared to United States (US)-Approved and European (EU)-Authorized Insulin Aspart.	Day 1 for 12 Hours
Time to Half-maximum After Maximum Observed Insulin Aspart Concentration Time to Half-Maximum After Maximum Observed Insulin Aspart Concentration (t50%-Late)	Evaluated additional Pharmacokinetic (PK) parameters of NKF-INS(A) compared to United Stated (US)-approved and European Union (EU)-authorized insulin aspart.	Day 1 for 12 Hours
The Terminal Elimination Half-life (t1/2)	Evaluated additional Pharmacokinetic (PK) parameters of NKF-INS(A) compared to United Stated (US)-approved and European Union (EU)-authorized insulin aspart.	Day 1 for 12 Hours
PK Parameters for Serum Insulin Aspart Concentrations: Area Under the Insulin Aspart Concentration-Time Curve to Maximum Insulin Aspart Concentration (Tmax)	Evaluated additional Pharmacokinetic (PK) parameters of NKF-INS(A) compared to United Stated (US)-approved and European Union (EU)-authorized insulin aspart.	Day 1 for 12 Hours
PK Parameters for Serum Insulin Aspart Concentrations: Area Under the Insulin Aspart Concentration-Time Curve AUC6-12h	Evaluated additional Pharmacokinetic (PK) parameters of NKF-INS(A) compared to United Stated (US)-approved and European Union (EU)-authorized insulin aspart.	Day 1 for 12 Hours

Collaborators and Investigators

• Sponsor: Xentria, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2024
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hypoglycemic Agents; Insulin Aspart
• Other Study ID Numbers: NKF-INS(A)-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes