A Study of LY900014 and Insulin Lispro With an External Continuous Subcutaneous Insulin Infusion System in Adult Participants With Type 1 Diabetes (PRONTO-Pump)

A Prospective, Randomized, Double-Blind, Crossover Comparison Evaluating Compatibility and Safety of LY900014 and Insulin Lispro With an External Continuous Subcutaneous Insulin Infusion System in Adult Patients With Type 1 Diabetes (PRONTO-Pump)

The purpose of this study is to evaluate the compatibility and safety of LY900014 and insulin lispro with an external continuous subcutaneous insulin infusion system in adult participants with type 1 diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Type 1
• Intervention / Treatment: Drug: LY900014; Drug: Insulin lispro

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41009
    • For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
  • Seville, Spain, 41003
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • California
    • Fresno, California, United States, 93720
      • Valley Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Childhood Diabetes
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates

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:

• Diagnosed with type 1 diabetes and have been using insulin continuously for at least 12 months.
• Using an insulin pump with 'rapid-acting insulin' for at least 6 months and using the same rapid-acting insulin for at least the past 30 days.
• Have experience using Continuous Glucose Monitoring (CGM) or Flash Glucose Monitoring (FGM) for at least 60 days during the past 12 months.
• Have hemoglobin A1c values ≤8.5%, as determined by the central laboratory at screening.
• Have a body mass index (BMI) of ≤35 kilograms per meter squared at screening.
• Have been using the MiniMed 530G or 630G (US) or the MiniMed 640G (EU) insulin pump for at least the past 30 days.

Exclusion Criteria:

• Have had more than 1 emergency treatment for very low blood glucose in the last 6 months.
• Have had more than 1 emergency treatment for poor glucose control (hyperglycemia or diabetic ketoacidosis) in the last 6 months.
• Have significant insulin resistance defined as having received a total daily dose of insulin >1.2 units per kilogram (U/kg) at screening, as determined by the average total daily insulin dose over the 3 days prior to screening divided by weight in kilograms based on investigator review of the participant's pump history.
• Have significant lipohypertrophy, lipoatrophy, or scars within the subcutaneous tissue in areas of infusion or have a history of abscess at an infusion site within the last 90 days prior to screening.
• Are receiving any oral or injectable medication intended for the treatment of diabetes mellitus other than rapid-acting analog insulin via CSII in the 90 days prior to screening. Occasional pen or syringe injection of insulin is allowed, for example, due to pump malfunction or unexplained hyperglycemia not responsive to pump correction bolus.
• Taking certain diabetes medications that are not allowed for study participation.
• Have major problems with heart, kidneys, liver, or have a blood disorder.
• Have had or are now being treated for certain types of cancer that prevents study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY900014; 100 units per milliliter (U/mL) LY900014 administered by individualized, continuous, subcutaneous insulin infusion (CSII)	Drug: LY900014; Administered by CSII; Other Names: Ultra-Rapid Lispro
Experimental: Insulin Lispro; 100 U/mL insulin lispro (Humalog®) administered by individualized CSII	Drug: Insulin lispro; Administered by CSII; Other Names: Humalog

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Infusion Set Failures	Infusion set failure events are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) >250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter [mmol/L]) that does not decrease within 1 hour following a correction bolus delivered via the pump during the 6 week treatment period. Aggregate rate was calculated for each participant as the total number of events while the participant is on study treatment divided by the days of exposure [last dose date and time -first dose date and time -duration of pump or treatment interruption] times 30.	6 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 1 Event of Infusion Set Failure	Infusion set failures are defined as premature infusion set changes, due to a pump occlusion alarm OR due to unexplained hyperglycemia with blood glucose (SMBG) >250mg/dL (13.9 mmol/L) that does not decrease within 1 hour following a correction bolus delivered via the pump.	6 Weeks
Rate of Premature Infusion Set Changes	Rate of premature infusion set changes.	6 Weeks
Time Interval Until Infusion Set Change	Time interval until infusion set change reflects the time interval in hours until infusion set change from first to last dose. MMRM model for post-baseline measures: Variable = Baseline + Period + Sequence + Strata(Region + Historical Use of SmartGuard/Threshold Suspend + HbA1c(<=7.3%, >7.3%)) + Treatment (Type III sum of squares).	6 Weeks
Ratio of Bolus/Total Insulin Dose	The bolus and total insulin doses for each visit was calculated as the mean of the doses for the last 3 days prior to the visit date that are entered in the eCRF. The bolus/total ratio was derived as the bolus dose divided by the total insulin dose at each visit.	6 Weeks
Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump	Interstitial glucose reduction rate (glucose reduction [mg/dL] per minute) within 4 hours following a non-meal-related correction bolus via the pump, from hyperglycemia (interstitial glucose >180 mg/dL [10 mmol/L]) to recovery (interstitial glucose ≤180 mg/dL).	6 Weeks
Number of Participants With Severe Hypoglycemic Events	Number of participants with severe hypoglycemic events. Severe hypoglycemia was defined as participants with an altered mental status and could not assist in their own care, may have been semiconscious or unconscious, or experienced coma with or without seizures, and the event required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Blood glucose measurements may not have been available during such an event, but neurological recovery attributable to the restoration of BG concentration to normal was considered sufficient evidence that the event was induced by a low BG concentration (BG ≤70 mg/dL [3.9 mmol/L]).	6 Weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 1-877-CTLILLY (1-877-285-4559) Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY900014 and Insulin Lispro With an External Continuous Subcutaneous Insulin Infusion System in Adult Participants With Type 1 Diabetes (PRONTO-Pump)

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2018
• Primary Completion (Actual): September 4, 2018
• Study Completion (Actual): September 4, 2018

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 8, 2019
• Last Update Submitted That Met QC Criteria: October 7, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: insulin pump
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: 16908; I8B-MC-ITSI (Other Identifier: Eli Lilly and Company); 2017-002374-39 (EudraCT Number)

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 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