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A Study Comparing LY900014 to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes Using Insulin Pump Therapy (PRONTO-Pump-2)

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ClinicalTrials.gov Identifier: NCT03830281
Recruitment Status : Completed
First Posted : February 5, 2019
Results First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE February 4, 2019
First Posted Date  ICMJE February 5, 2019
Results First Submitted Date  ICMJE January 4, 2021
Results First Posted Date  ICMJE January 22, 2021
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE February 14, 2019
Actual Primary Completion Date January 6, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2021)
Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 16 [ Time Frame: Baseline, Week 16 ]
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Pooled Country + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
Original Primary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, Week 16 ]
Change from baseline in HbA1c
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2021)
  • Change From Baseline in 1-hour Postprandial Glucose (PPG) During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand at Week 16 [ Time Frame: Baseline, Week 16 ]
    A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 1-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of variance (ANCOVA) model with independent variables: Baseline + Pooled Country + Hemoglobin A1C Stratum + Personal CGM/FGM use during study Flag + Treatment (Type III sum of squares).The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
  • Change From Baseline in 2-hour PPG During MMTT Efficacy Estimand at Week 16 [ Time Frame: Baseline, Week 16 ]
    A standardized MMTT was used to characterize postprandial glucose control following administration of the study insulin. Serum glucose measured at 2-hour timepoint after the start of meal minus fasting serum glucose. Least Squares (LS) mean was determined by analysis of variance (ANCOVA) model with independent variables: Baseline + Pooled Country + Hemoglobin A1C Stratum + Personal CGM/FGM use during study Flag + Treatment (Type III sum of squares).The efficacy estimand included participant data when baseline and at least one post-baseline measurement were available prior to permanent discontinuation of study drug.
  • Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL Efficacy Estimand at Week 16 [ Time Frame: Week 16 ]
    Percentage of time with sensor glucose values between 70 and 180 mg/dL using continuous glucose monitoring (CGM). Least square (LS) mean difference will provided for CGM data normalized to a 24hrs period. Daytime: 0600 hours to midnight (06:00:00-23:59:59 on the 24-hour clock). Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates: Baseline + Pooled Country + Hemoglobin A1C Stratum + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares).
  • Rate of Severe Hypoglycemia at Week 16 [ Time Frame: Baseline through Week 16 ]
    Severe hypoglycemia is defined as an event requiring assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. During these episodes, the participant has an altered mental status and cannot assist in his or her own care, or may be semiconscious or unconscious, or experience coma with or without seizures, and may require parenteral therapy. Rate of severe hypoglycemia events per 100 years during a defined period was calculated by total number of severe hypoglycemia episodes within the period divided by the cumulative days on treatment from all participants within a treatment group *36525.
  • Rate of Documented Symptomatic Hypoglycemia at Week 16 [ Time Frame: Baseline through Week 16 ]
    Documented symptomatic hypoglycemia is an event during which typical symptoms of hypoglycemia are accompanied by blood glucose (BG) of <54 mg/dL [3.0 millimole per liter (mmol/L)]. The rate of documented symptomatic hypoglycemia was estimated by negative binomial model: number of episodes = treatment with log (treatment exposure in days/365.25) as an offset variable.
  • Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at Week 16 [ Time Frame: Baseline, Week 16 ]
    1,5-anhydroglucitol (1,5-AG) is a marker of short-term glycemic control especially postprandial hyperglycemia. 1,5-AG accurately predicts rapid changes in glycemia and is tightly associated with glucose fluctuations and postprandial glucose. LS Mean was calculated using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (Pooled Country + Hemoglobin A1C Stratum + Personal continuous glucose Monitor (CGM) or Flash glucose monitor (FGM) use during study flag), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The analysis included data collected prior to permanent discontinuation of study drug.
  • Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at Week 16 [ Time Frame: Baseline, Week 16 ]
    SMBG 10-point profiles were measured at fasting, 1-hour post morning meal, 2-hours post morning meal, pre midday meal, 1-hour post midday meal, 2-hours post midday meal, pre evening meal, 1-hour post evening meal, 2-hours post evening meal, and bedtime. LS Mean was analyzed using mixed model repeated measures (MMRM) including fixed class effects of treatment, strata (pooled country, HbA1c stratum : less than or equal to (≤)7.5%, greater than (>)7.5% and participant's personal CGM or FGM use during the study), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. The efficacy estimand included participant data when baseline and at least one post-baseline measurement prior to permanent discontinuation of study drug.
  • Change From Baseline in Insulin Dose at Week 16 [ Time Frame: Baseline, Week 16 ]
    LS mean was determined by MMRM model with covariates: Baseline + Pooled Country + + Hemoglobin A1C Stratum + Personal CGM or FGM use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). The analysis included data prior to permanent discontinuation of study drug.
  • Change From Baseline in Bolus/Total Insulin Dose Ratio at Week 16 [ Time Frame: Baseline, Week 16 ]
    The bolus/total ratio was derived as the bolus dose divided by the total insulin dose at each visit. LS mean was determined by MMRM model with covariates: Baseline + Pooled Country + + Hemoglobin A1C Stratum + Personal CGM or FGM use during study flag + Treatment + Time + Treatment*Time (Type III sum of squares). The analysis included data prior to permanent discontinuation of study drug.
  • Percentage of Participants With HbA1c <7% [ Time Frame: Week 16 ]
    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
  • Percentage of Participants With at Least 1 Pump Occlusion Alarm That Leads to an Unplanned Infusion Set Change [ Time Frame: Baseline through Week 16 ]
    Percentage of participants with at least 1 pump occlusion alarm that leads to an unplanned infusion set change was evaluated.
  • Percentage of Participants With at Least 1 Event of Unexplained Hyperglycemia >300 mg/dL Confirmed by SMBG That Leads to an Unplanned Infusion Set Change [ Time Frame: Baseline through Week 16 ]
    Percentage of participants with at least 1 event of unexplained hyperglycemia >300 milligrams per deciliter (mg/dL) confirmed by SMBG that leads to an unplanned infusion set change was evaluated.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
  • 1-hour Postprandial Glucose (PPG) Excursion during Mixed-Meal Tolerance Test (MMTT) [ Time Frame: Week 16 ]
    1-hour PPG excursion during MMTT
  • 2-hour PPG Excursion during MMTT [ Time Frame: Week 16 ]
    2-hour PPG excursion during MMTT
  • Rate of Severe Hypoglycemia [ Time Frame: Baseline through Week 16 ]
    Rate of severe hypoglycemia
  • Rate of Documented Symptomatic Hypoglycemia [ Time Frame: Baseline through Week 16 ]
    Rate of documented symptomatic hypoglycemia
  • Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) [ Time Frame: Baseline, Week 16 ]
    Change from baseline in 1,5-AG
  • Change from Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values [ Time Frame: Baseline, Week 16 ]
    Change from baseline in 10-point SMBG values
  • Change from Baseline in Bolus/Total Insulin Dose Ratio [ Time Frame: Baseline, Week 16 ]
    Change from baseline in bolus/total insulin dose ratio
  • Percentage of Participants with HbA1c <7% and ≤6.5% [ Time Frame: Week 16 ]
    Percentage of participants with HbA1c <7% and ≤6.5%
  • Percentage of Time with Sensor Glucose Values between 71 and 180 milligrams per deciliter (mg/dL) [ Time Frame: Week 16 ]
    Percentage of time with sensor glucose values between 71 and 180 mg/dL
  • Percentage of Participants With at Least 1 Pump Occlusion Alarm That Leads to an Unplanned Infusion Set Change [ Time Frame: Baseline through Week 16 ]
    Percentage of participants with at least 1 pump occlusion alarm that leads to an unplanned infusion set change
  • Percentage of Participants With at Least 1 Event of Unexplained Hyperglycemia >300 mg/dL Confirmed by SMBG That Leads to an Unplanned Infusion Set Change [ Time Frame: Baseline through Week 16 ]
    Percentage of participants with at least 1 event of unexplained hyperglycemia >300 milligrams per deciliter (mg/dL) confirmed by SMBG that leads to an unplanned infusion set change
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing LY900014 to Insulin Lispro (Humalog) in Adults With Type 1 Diabetes Using Insulin Pump Therapy
Official Title  ICMJE A Prospective, Randomized, Double-Blind Comparison of LY900014 to Humalog in Adults With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion
Brief Summary The reason for this study is to compare the study drug LY900014 to insulin lispro (Humalog) when both are used in insulin pump therapy in adults with type 1 diabetes (T1D).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Ultra-Rapid Lispro
    Administered SC
    Other Names:
    • LY900014
    • Insulin lispro
  • Drug: Insulin Lispro
    Administered SC
    Other Names:
    • Humalog
    • LY275585
Study Arms  ICMJE
  • Active Comparator: Insulin Lispro (Humalog)
    Participants received individual dose of 100 U/mL insulin lispro (Humalog) by CSII; where mealtime boluses were delivered 0 to 2 minutes prior to the start of each meal, with basal infusion rates 24 hours/day, and correction boluses as necessary.
    Intervention: Drug: Insulin Lispro
  • Experimental: Ultra-Rapid Lispro
    Participants received individual dose of 100 units per milliliter (U/mL) ultra rapid lispro by continuous subcutaneous insulin infusion (CSII); where mealtime boluses were delivered 0 to 2 minutes prior to the start of each meal, with basal infusion rates 24 hours/day, and correction boluses as necessary.
    Intervention: Drug: Ultra-Rapid Lispro
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2021)
471
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2019)
526
Actual Study Completion Date  ICMJE January 6, 2020
Actual Primary Completion Date January 6, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have been diagnosed with T1D and continuously using insulin for at least 1 year
  • Have been using CSII therapy for a minimum of 6 months
  • Currently treated with <100 Units of one of following rapid-acting analog insulin via CSII for at least the past 30 days: insulin lispro U-100, insulin aspart, fast-acting insulin aspart, insulin glulisine
  • Must be using a MiniMed 530G (US), Paradigm Revel (US), or MiniMed 630G (US and Canada), MiniMed 640G or Paradigm Veo (select countries outside the US), insulin pump for at least the past 90 days

Exclusion Criteria:

  • Have hypoglycemia unawareness
  • Have had more than 1 episode of severe hypoglycemia within 6 months prior to screening
  • Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within 6 months prior to screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   France,   Germany,   Hungary,   Israel,   Italy,   Puerto Rico,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03830281
Other Study ID Numbers  ICMJE 16315
I8B-MC-ITRO ( Other Identifier: Eli Lilly and Company )
2015-005358-36 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: http://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: 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) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP