A Study of Mealtime Insulin LY900014 in Participants With Type 2 Diabetes Using Continuous Glucose Monitoring (PRONTO-Time in Range)

A Study of LY900014 in Participants With Type 2 Diabetes Using Continuous Glucose Monitoring

This study is being done to evaluate glycemic control in participants with type 2 diabetes who are taking mealtime insulin LY900014 in combination with long-acting insulin glargine. Participants will use continuous glucose monitoring (CGM) (Freestyle Libre 14-day system) during the study.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: LY900014; Drug: Insulin Glargine

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Advanced Clinical Research, LLC
  • Manati, Puerto Rico, 00674
    • Manati Center for Clinical Research Inc
• United States
  • California
    • Concord, California, United States, 94520
      • John Muir Physician Network Clinical Research Center
    • Escondido, California, United States, 92025
      • AMCR Institute
    • Fresno, California, United States, 93720
      • Valley Endocrine, Fresno
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
    • Ventura, California, United States, 93003
      • Coastal Metabolic Research Centre
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven
  • Florida
    • Hollywood, Florida, United States, 33021
      • Encore Medical Research
    • New Port Richey, Florida, United States, 34652
      • Sun Coast Clinical Research, Inc
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
    • Macon, Georgia, United States, 31210
      • East Coast Institute for Research at The Jones Center
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Illinois
    • Springfield, Illinois, United States, 62711
      • Central Illinois Diabetes and Clinical Research a Division of Prairie Education and Research Cooperative
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Maryland Cardiovascular Specialists
    • Rockville, Maryland, United States, 20852
      • Endocrine and Metabolic Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center Tenaya
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Tenaya
  • New York
    • New York, New York, United States, 10016
      • Research NYC, Inc
    • Syracuse, New York, United States, 13210
      • Suny Health Science Center at Syracuse
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Cataret Medical Group
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Intend Research, LLC
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology, P.A.
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • Houston, Texas, United States, 77079
      • Endocrine Ips, Pllc
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine and Research
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants diagnosed (clinically) with type 2 diabetes mellitus (T2D) for at least 1 year prior to screening.

• Have been treated with basal-bolus multiple daily injection (MDI) therapy for at least 90 days prior to screening including:

  • Basal insulin glargine U-100, in combination with bolus insulin analog (insulin lispro, insulin aspart, or insulin glulisine) with meals.
  • Participant must have been treated with the same type of allowed bolus insulin analog for at least 30 days prior to screening.

• Participants may be treated with up to 3 of the following oral antihyperglycemic medications (OAMs) for T2D in accordance with local regulations:

  1. Metformin
  2. Dipeptidyl peptidase-4 (DPP-4) inhibitor
  3. sodium glucose cotransporter 2 (SGLT2) inhibitor
  4. oral glucagon-like peptide 1 (GLP-1) agonist
• Doses of OAMs are required to have been stable for at least 90 days prior to screening.
• Participants may be treated with injectable GLP-1 receptor agonist for T2D in accordance with local regulations. The GLP-1 receptor agonist dose is required to have been stable for at least 90 days prior to screening.
• Have an HbA1c value ≥7.5% and ≤10% according to the central laboratory at screening.

Exclusion Criteria:

• Have been diagnosed at any time with type 1 diabetes mellitus or latent autoimmune diabetes in adults.
• Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to screening.
• Have had any episode of hyperglycemic hyperosmolar state or diabetic ketoacidosis within 6 months prior to screening.
• Have hypoglycemia unawareness as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY900014; LY900014 (100 units/milliliter (U/mL)) is a mealtime insulin administered subcutaneously (SC) 0-2 minutes prior to each meal in combination with insulin glargine (100 U/mL) SC as long-acting insulin. Mealtime (bolus) and long-acting (basal) insulin doses were titrated to achieve glucose targets during the study.	Drug: LY900014; Administered SC; Drug: Insulin Glargine; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percentage of Time With Continuous Glucose Monitoring (CGM) Sensor Glucose Values Between 70-180 Milligrams/Deciliter (mg/dL) (3.9-10.0 Millimoles/Liter [mmol/L]) (Both Inclusive) During Daytime Period at Week 12	Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Time as variables.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values Between 70-180 mg/dL (3.9-10.0 mmol/L) (Both Inclusive) During the 24-hour Period at Week 12	LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values <54 mg/dL (<3.0 mmol/L) During Daytime and 24-hour Periods at Week 12	LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Percentage of Time With CGM Sensor Glucose Values >180 mg/dL (>10.0 mmol/L) During Daytime and 24-hour Period at Week 12	LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Percentage of Time With CGM Sensor Glucose Value >250 mg/dL (>13.9 mmol/L) During Daytime and 24-hour Period at Week 12	LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-1 Hour at Week 12	iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from Glucose measures taken every 15 minutes from 0 to 1 hour after meal using CGM sensor (i.e., 0, 15, 30, 45, 60 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate.	Baseline, Week 12
Change From Baseline in Postprandial Incremental Area Under the Glucose Curve (iAUC) 0-2 Hour at Week 12	iAUC reflects the metabolic control and is calculated using the standard trapezoidal rule from glucose measures taken every 15 minutes from 0 to 2 hours after meal using CGM sensor (i.e., 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after meal). LS mean was determined by ANCOVA (analysis of covariance) with Baseline as covariate.	Baseline, Week 12
Percentage of Participants With HbA1c <7% and ≤6.5%	HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 12
Change From Baseline in Daily Insulin Dose at Week 12	LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Bolus/Total Insulin Dose Percentage at Week 12	LS mean was determined by MMRM model with Baseline + Time as variables.	Baseline, Week 12
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) - Glycemic Control Domain Score at Week 12	The ITSQ is a 22-item questionnaire that assesses treatment satisfaction for subjects taking insulin under 5 domains: Inconvenience of Regimen [IR - 5 items], Lifestyle Flexibility [LF - 3 items], Glycemic Control [GC - 3 items], Hypoglycemic Control [HC - 5 items], Insulin Delivery Device [IDD - 6 items]. Each Item is measured on a 7-point scale, with scores ranging for IR from 5 to 35, LF from 3 to 21, GC from 3 to 21, HC from 5 to 35, IDD from 6 to 42. Lower scores reflect better outcomes. Data presented are for Glycemic Control Domain Scores transformed on a 0-100 scale, where transformed domain score = 100×[(7-raw domain score)/6]. Higher scores indicate better glycemic control. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as a covariate.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of Mealtime Insulin LY900014 in Participants with Type 2 Diabetes Using Continuous Glucose Monitoring (PRONTO-Time in Range)

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): February 4, 2022
• Study Completion (Actual): February 4, 2022

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Glargine
• Other Study ID Numbers: 17428 (Other Identifier: City of Hope Comprehensive Cancer Center); I8B-MC-ITSW (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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