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

• ClinicalTrials.gov Identifier: NCT03433677
• Recruitment Status: Completed
• First Posted: February 14, 2018
• Results First Posted: October 8, 2019
• Last Update Posted: October 8, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Diabetes Type 1	Drug: LY900014; Drug: Insulin lispro	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 21, 2018
• Actual Primary Completion Date: September 4, 2018
• Actual Study Completion Date: September 4, 2018

Arms and Interventions

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 Name: Ultra-Rapid Lispro
Experimental: Insulin Lispro; 100 U/mL insulin lispro (Humalog®) administered by individualized CSII	Drug: Insulin lispro; Administered by CSII; Other Name: Humalog

Outcome Measures

Primary Outcome Measures :

1. Rate of Infusion Set Failures [ Time Frame: 6 Weeks ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With at Least 1 Event of Infusion Set Failure [ Time Frame: 6 Weeks ]
   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.
2. Rate of Premature Infusion Set Changes [ Time Frame: 6 Weeks ]
   Rate of premature infusion set changes.
3. Time Interval Until Infusion Set Change [ Time Frame: 6 Weeks ]
   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).
4. Ratio of Bolus/Total Insulin Dose [ Time Frame: 6 Weeks ]
   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.
5. Interstitial Glucose Reduction Rate From Hyperglycemia Following a Non-Meal-Related Correction Bolus Delivered Via the Pump [ Time Frame: 6 Weeks ]
   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. Number of Participants With Severe Hypoglycemic Events [ Time Frame: 6 Weeks ]
   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]).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Valley Research

Fresno, California, United States, 93720

United States, Colorado

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, United States, 80045

United States, Georgia

Atlanta Diabetes Associates

Atlanta, Georgia, United States, 30318

Spain

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.

Sevilla, Spain, 41009

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.

Seville, Spain, 41003

Sponsors and Collaborators

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

  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:

Study Protocol  [PDF] January 12, 2018

Statistical Analysis Plan  [PDF] August 29, 2018

More Information

Additional Information:

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

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03433677
• Other Study ID Numbers: 16908; I8B-MC-ITSI ( Other Identifier: Eli Lilly and Company ); 2017-002374-39 ( EudraCT Number )
• First Posted: February 14, 2018
• Results First Posted: October 8, 2019
• Last Update Posted: October 8, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• 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; Statistical Analysis Plan (SAP); 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 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: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eli Lilly and Company:

insulin pump

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin Lispro; Hypoglycemic Agents; Physiological Effects of Drugs