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CompletedNCT03286751Updated May 1, 2020Results posted

A Comparative Study of LY900014 to Insulin Lispro (Humalog) in Healthy Participants

A Phase 1 interventional study of LY900014 and Insulin Lispro in Diabetes Mellitus, Type 2, sponsored by Eli Lilly and Company. Completed at 2 sites in Germany. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-05-01.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This study compares LY900014, a drug that lowers blood sugar, with insulin lispro (Humalog). Both drugs are given by injection under the skin of the abdomen. The study will be conducted in healthy people to investigate how quickly and how much LY900014 is absorbed and the effect of different doses of LY900014 on blood sugar levels in comparison with insulin lispro. The study will last about 7 to 12 weeks for each participant, including screening and follow up. Screening is required within 28 days prior to entering the study.

02

Conditions studied

  • Diabetes Mellitus, Type 2
03

Who can participate

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

Inclusion criteria

  • Healthy male or a female (not pregnant and agreeable to take birth control measures until one month after study completion)
  • Have a body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m²)
  • Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results
  • Are nonsmokers, have not smoked for at least 6 months prior to entering the study

Exclusion criteria

Exclusion Criteria:

  • Are currently participating in or completed a clinical trial within the last 30 days
  • Have previously participated or withdrawn from this study
  • Have donated blood or have blood loss of more than 500 mL within the past 3 months
04

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
42 participants (actual)

Study arms

  • Experimental
    LY900014

    Single dose of 7 units (U), 15 U, and 30 U of LY900014 administered subcutaneously (SC) in three of six periods.

    Drug: LY900014

  • Active comparator
    Insulin Lispro (Humalog)

    Single dose of 7 U, 15 U, and 30 U of insulin lispro administered SC in three of six periods.

    Drug: Insulin Lispro

Interventions

  • DrugLY900014

    Administered SC

    Also known as: Ultra-Rapid Lispro

  • DrugInsulin Lispro

    Administered SC

    Also known as: LY275585, Humalog

05

What researchers measure

Primary outcomes

  1. Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC)

    Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose \[AUC(0-10h)\]

    Time frame: Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose

Secondary outcomes

  1. Glucodynamics: Total Amount of Glucose Infused (Gtot)

    Glucodynamics: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp

    Time frame: Day 1: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose

06

Results

Posted May 1, 2020

Participant flow

Period 1
Participant flow — Period 1
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started777777
Received at least one dose of study drug777777
Completed777777
Not completed000000
Washout Period 1
Participant flow — Washout Period 1
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started777777
Completed777767
Not completed000010
Withdrew: Withdrawal by subject000010
Period 2
Participant flow — Period 2
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started777767
Completed777767
Not completed000000
Washout Period 2
Participant flow — Washout Period 2
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started777767
Completed767767
Not completed010000
Withdrew: Personal reasons010000
Period 3
Participant flow — Period 3
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767767
Completed767767
Not completed000000
Washout Period 3
Participant flow — Washout Period 3
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767767
Completed767767
Not completed000000
Period 4
Participant flow — Period 4
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767767
Completed767767
Not completed000000
Washout Period 4
Participant flow — Washout Period 4
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767767
Completed767767
Not completed000000
Period 5
Participant flow — Period 5
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767767
Completed767767
Not completed000000
Washout Period 5
Participant flow — Washout Period 5
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767767
Completed767757
Not completed000010
Withdrew: Adverse event000010
Period 6
Participant flow — Period 6
MilestoneSequence 1: ABFCEDSequence 2: BCADFESequence 3: CDBEAFSequence 4: DECFBASequence 5: EFDACBSequence 6: FAEBDC
Started767757
Completed767757
Not completed000000

Outcome measures

PrimaryPharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC)

Pharmacokinetics: Insulin Lispro Area Under the Concentration Curve From Time Zero to 10 Hours Post Dose \[AUC(0-10h)\]

Time frame:
Day 1: Pre-dose, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 90, 120, 150, 180, 210, 240, 300, 360, 420, 480, 540, and 600 minutes post-dose
Reported as:
Geometric mean · picomole * hour per liter(pmol*/L)
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC)
picomole * hour per liter(pmol*/L)7 U Humalog7 U LY90001415 U Humalog15 U LY90001430 U Humalog30 U LY900014
Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Versus Time Curve (AUC)649 ± 16656 ± 171400 ± 191450 ± 173050 ± 183180 ± 20
Statistical analysis
  • 7 U Humalog vs 7 U LY900014 · Mixed Models Analysis · p = 0.5495 · Ratio of geometric lsmeans: 1.01 · 95% CI 0.974 to 1.05
  • 15 U Humalog vs 15 U LY900014 · Mixed Models Analysis · p = 0.2236 · Ratio of geometric lsmeans: 1.02 · 95% CI 0.986 to 1.06
  • 30 U Humalog vs 30 U LY900014 · Mixed Models Analysis · p = 0.0727 · Ratio of geometric lsmeans: 1.03 · 95% CI 0.997 to 1.07
SecondaryGlucodynamics: Total Amount of Glucose Infused (Gtot)

Glucodynamics: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp

Time frame:
Day 1: Every minute starting from the pre-dose and throughout the duration of the clamp until 10 hours post-dose
Reported as:
Geometric mean · milligrams per kilogram (mg/kg)
Glucodynamics: Total Amount of Glucose Infused (Gtot)
milligrams per kilogram (mg/kg)7 U Humalog7 U LY90001415 U Humalog15 U LY90001430 U Humalog30 U LY900014
Glucodynamics: Total Amount of Glucose Infused (Gtot)1120 ± 531080 ± 601970 ± 441860 ± 453290 ± 323030 ± 36
Statistical analysis
  • 7 U Humalog vs 7 U LY900014 · Mixed Models Analysis · p = 0.5749 · Ratio of geometric lsmeans: 0.97 · 95% CI 0.87 to 1.08
  • 15 U Humalog vs 15 U LY900014 · Mixed Models Analysis · p = 0.1578 · Ratio of geometric lsmeans: 0.92 · 95% CI 0.83 to 1.03
  • 30 U Humalog vs 30 U LY900014 · Mixed Models Analysis · p = 0.1351 · Ratio of geometric lsmeans: 0.92 · 95% CI 0.83 to 1.03

Adverse events

Collected over Baseline to study completion (up to 12 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
7 U LY9000140/40 (0%)0/40 (0%)7/40 (17.5%)
15 U LY9000140/40 (0%)0/40 (0%)5/40 (12.5%)
30 U LY9000140/41 (0%)0/41 (0%)14/41 (34.1%)
7 U Humalog0/40 (0%)0/40 (0%)8/40 (20%)
15 U Humalog0/41 (0%)0/41 (0%)6/41 (14.6%)
30 U Humalog0/40 (0%)0/40 (0%)5/40 (12.5%)
Most frequent other events
Most frequent other events
Event7 U LY90001415 U LY90001430 U LY9000147 U Humalog15 U Humalog30 U Humalog
HeadacheNervous system disorders6/404/406/418/403/413/40
Injection site reactionGeneral disorders1/401/406/410/402/410/40
NauseaGastrointestinal disorders1/402/403/411/401/412/40

Baseline characteristics

All Participants who received at least one dose of study drug.

Age, Continuous
Age, Continuous(years)Overall
Mean41.9 ± 11.6
Sex: Female, Male
Sex: Female, Male(Participants)Overall
Female15
Male27
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Overall
Hispanic or Latino2
Not Hispanic or Latino40
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Overall
American Indian or Alaska Native2
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White40
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Overall
Germany42
07

Study locations

2 sites
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
    Mainz, 55116, Germany
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
    Neuss, 41460, Germany
08

References and documents

Publications

  • Leohr J, Dellva MA, Carter K, LaBell E, Linnebjerg H. Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs Humalog(R) Consistently Across Study Populations: A Pooled Analysis of Pharmacokinetic and Glucodynamic Data. Clin Pharmacokinet. 2021 Nov;60(11):1423-1434. doi: 10.1007/s40262-021-01030-0. Epub 2021 May 27. PubMed 34041713 ↗
  • Leohr J, Dellva MA, LaBell E, Coutant DE, Klein O, Plum-Moerschel L, Zijlstra E, Linnebjerg H. Pharmacokinetic and Glucodynamic Responses of Ultra Rapid Lispro vs Lispro Across a Clinically Relevant Range of Subcutaneous Doses in Healthy Subjects. Clin Ther. 2020 Sep;42(9):1762-1777.e4. doi: 10.1016/j.clinthera.2020.07.005. Epub 2020 Sep 6. PubMed 32900535 ↗

Study documents

  • Study protocol · Jun 26, 2017
  • Statistical analysis plan · Apr 18, 2018

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

09

Registry details

Key details

Study ID
NCT03286751
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Sep 18, 2017
Start date
Oct 13, 2017
Primary completion
Feb 6, 2018
Completion
Feb 6, 2018
Results posted
May 1, 2020
Last update
May 1, 2020

Study contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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