A Study of Insulin Glargine (LY2963016) in Healthy Chinese Participants

Relative Bioavailability of LY2963016 to LANTUS® After Single-Dose Subcutaneous Administration in Healthy Chinese Subjects

The purpose of this study is to compare a study drug known as Insulin glargine with Lantus in healthy Chinese participants. Blood samples will be taken to compare how the body handles the drugs and how they affect blood sugar levels. Side effects and tolerability will be documented. The study will last at least 18 days, not including screening. Screening is required within 4 weeks prior to the start of the study.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Insulin Glargine; Drug: Lantus

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are native Chinese men or women. Native Chinese is defined as a participant who has both parents and all 4 grandparents of Chinese origin.

• For females of childbearing potential (defined as not surgically sterilised and between menarche and 1-year postmenopause) only:

  • Negative serum pregnancy test at the time of screening.
  • Are not lactating.
  • Intend not to become pregnant during the study.
  • Are sexually inactive or have practiced a reliable method of birth control for at least 6 weeks prior to screening.
  • Agree to continue to use a reliable method of birth control (as determined by the investigator) during the study.

• For females not of childbearing potential, must be:

  • Surgically sterile, defined as having had a hysterectomy or bilateral oophorectomy or tubal ligation, and/or
  • Menopausal, defined as having had no menses for at least 1 year, or a plasma follicular stimulating hormone value of >40 milli-international units per milliliter (mIU/mL) and no menses for at least 6 months, unless the participant is taking hormone-replacement therapy.
• Having fasting plasma glucose <110 milligrams per deciliter (mg/dL) (<6.1 millimoles per liter [mmol/L]) and 2-hour glucose level <140 mg/dL (<7.8 mmol/L) on the 75 grams (g) oral glucose tolerance test.
• Have a body mass index (BMI) between 18 and 28 kilograms per meter squared (kg/m²), inclusive, at screening.
• Are nonsmokers, have not smoked for at least 6 months prior to entering the study, and agree not to smoke (cigars, cigarettes, or pipes) or use smokeless tobacco for the duration of the study.
• Have normal blood pressure and pulse rate at screening, as determined by the investigator.
• Have an electrocardiogram (ECG), at screening, considered as within normal limits by the investigator.
• Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.

Exclusion Criteria:

• Have a history of first-degree relatives known to have diabetes mellitus.
• Have known allergies to insulin glargine or its excipients, or related drugs, or heparin, or have a history of relevant allergic reactions of any origin.
• Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
• Show evidence of human immunodeficiency virus infection (HIV) and/or positive human HIV antibodies.
• Have positive hepatitis B surface antigen.
• Have donated >400 mL of blood in the last 6 months or donated >100 mL within the last 30 days.
• Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to stop alcohol consumption while resident in the clinical research unit (CRU) (1 unit = 12 ounces or 360 mL of beer; 5 ounces or 150 mL of wine; 1.5 ounces or 45 mL of distilled spirits).
• Intend to use: prescription medication or over-the-counter medication or Chinese traditional medicine within 14 days before dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement, or birth control methods). If this situation arises, an otherwise suitable participant may be included at the discretion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Glargine; Participants received 0.5 units per kilogram (U/kg) of Insulin Glargine subcutaneously (SC).	Drug: Insulin Glargine; Administered SC; Other Names: LY2963016; Basaglar
Active Comparator: Lantus; Participants received 0.5 U/Kg of Lantus subcutaneously.	Drug: Lantus; Administered SC; Other Names: Insulin Glargine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin Glargine and Lantus	Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Insulin glargine and Lantus.	-0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose
PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin Glargine and Lantus	PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Insulin glargine and Lantus.	-0.5 and 0 hours predose; 0.5, 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics (PD): Total Amount of Glucose Infused (Gtot)	Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of Insulin glargine or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.	30 minutes predose through 24 hours postdose
PD: Maximum Glucose Infusion Rate (Rmax)	Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain target blood glucose level and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of Insulin glargine or Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight.	30 minutes predose through 24 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Liu H, Wang F, Ji Y, Ma T, Li H, Linnebjerg H, Chua L, Tham LS, Yu Y. A Euglycemic Glucose Clamp Study to Evaluate the Bioavailability of LY2963016 Relative to Insulin Glargine in Healthy Chinese Subjects. Clin Pharmacol Drug Dev. 2021 Dec;10(12):1452-1459. doi: 10.1002/cpdd.1014. Epub 2021 Aug 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): November 4, 2019
• Study Completion (Actual): November 4, 2019

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: November 15, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: 13877; I4L-MC-ABEF (Other Identifier: Eli Lilly and Company)

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