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

Type 1 Diabetes Mellitus Clinical Trial

— PRONTO-Pump-2  

Official title:

A Prospective, Randomized, Double-Blind Comparison of LY900014 to Humalog in Adults With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03830281
• Other study ID #: 16315
• Secondary ID: I8B-MC-ITRO2015-
• Status: Completed
• Phase: Phase 3
• Start date: February 14, 2019
• Est. completion date: January 6, 2020

Study information

• Verified date: January 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 471
• Est. completion date: January 6, 2020
• Est. primary completion date: January 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Ultra-Rapid Lispro
Administered SC
• Insulin Lispro
Administered SC

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Barwon Health - The Geelong Hospital	Geelong	Victoria
Australia	The AIM Centre	Merewether	New South Wales
Australia	GP Plus Marion	Oaklands Park	South Australia
Austria	VIVIT Institut am LKH Feldkirch	Feldkirch	Vorarlberg
Austria	Universitätsklinikum Graz	Graz	Steiermark
Austria	Universitätsklinikum Salzburg	Salzburg
Austria	KA Rudolfstiftung	Vienna
Canada	LMC Endocrinology Centres Ltd.	Barrie	Ontario
Canada	LMC Endocrinology Centres Ltd.	Concord	Ontario
Canada	IRCM	Montreal	Quebec
Canada	LMC Endocrinology Centres	Oakville	Ontario
Canada	LMC Endocrinology Centres Ltd.	Toronto	Ontario
Canada	LMC Endocrinology Centres Ltd.	Ville St-Laurent	Quebec
France	Clinique Hotel Dieu	Le Creusot
France	Centre hospitalier universitaire Lapeyronie	Montpellier Cedex 5
France	Hopital Cochin	Paris CEDEX 14
France	Hôpital de HautePierre	Strasbourg
France	CHU Toulouse Hopital de Rangueil	Toulouse	Cedex 9
France	Groupe hospitalier mutualiste Les Portes du sud	Venissieux
Germany	Diabetespraxis Prenzlauer Allee	Berlin
Germany	Diabetologische Schwerpunktpraxis B. Scholz/Dr. B. Paschen	Hamburg
Germany	Gemeinschaftspraxis für innere Medizin und Diabetologie	Hamburg
Germany	Praxis Dr. Kempe - Dr. Stemler	Ludwigshafen am Rhein	Rheinland-Pfalz
Germany	Institut für Diabetesforschung Münster GmbH	Münster	Nordrhein-Westfalen
Germany	RED-Institut GmbH	Oldenburg	Schleswig-Holstein
Germany	Arztpraxis Dr. Cornelia Marck	Pohlheim	Hessen
Germany	Schwerpunktpraxis Diabetes	Saint Ingbert-Oberwürzbach	Saarland
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	ClinDiab Kft.	Budapest
Hungary	TRANTOR 99 Bt.	Budapest
Hungary	UNO Medical Trials Kft.	Budapest
Israel	Soroka Medical Center - Pediatric Outpatient Clinic	Beer-Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Schneider Medical Center	Petah Tiqva
Israel	Sheba Medical Center	Ramat Gan
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Ospedale San Giovanni di Dio	Olbia
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza	Roma
Puerto Rico	Advanced Clinical Research, LLC	Bayamon
Puerto Rico	Centro de Endocrinologia Alcantara Gonzalez	Lomas Verdes
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Universitari Arnau de Vilanova	Lleida	Cataluña
Spain	Hospital Universitario La Paz	Madrid
Spain	Corporació Sanitaria Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado
United States	Texas Diabetes and Endocrinology-Austin South	Austin	Texas
United States	Northwestern Feinberg School of Medicine	Chicago	Illinois
United States	John Muir Physician Network Clinical Research Center	Concord	California
United States	ALL Medical Research, LLC	Cooper City	Florida
United States	Dallas Diabetes Endocrine Center	Dallas	Texas
United States	Private: Dr. Larry Stonesifer	Federal Way	Washington
United States	Valley Research	Fresno	California
United States	Marin Endocrine Associates	Greenbrae	California
United States	Physicians East	Greenville	North Carolina
United States	East West Medical Institute	Honolulu	Hawaii
United States	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho
United States	Diabetes and Endocrine Associates	La Mesa	California
United States	First Valley Medical Group	Lancaster	California
United States	Palm Research Center	Las Vegas	Nevada
United States	Palm Research Center	Las Vegas	Nevada
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	Southern New Hampshire Diabetes and Endocrinology	Nashua	New Hampshire
United States	Sun Coast Clinical Research, Inc	New Port Richey	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Rainier Clinical Research Center	Renton	Washington
United States	Endocrine and Metabolic Consultants	Rockville	Maryland
United States	Endocrine Research Solutions, Inc.	Roswell	Georgia
United States	Texas Diabetes and Endocrinology, P.A.	Round Rock	Texas
United States	Center of Excellence in Diabetes & Endocrinology	Sacramento	California
United States	Prairie Education and Research Cooperative	Springfield	Illinois
United States	Tacoma Center for Arthritis Research, PS	Tacoma	Washington
United States	University Clinical Investigators, Inc.	Tustin	California
United States	Coastal Metabolic Research Centre	Ventura	California
United States	Iderc, P.L.C.	West Des Moines	Iowa
United States	Metabolic Research Institute Inc.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Germany,  Hungary,  Israel,  Italy,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at 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.	Baseline, Week 16
Secondary	Change From Baseline in 1-hour Postprandial Glucose (PPG) During Mixed-Meal Tolerance Test (MMTT) Efficacy Estimand at 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.	Baseline, Week 16
Secondary	Change From Baseline in 2-hour PPG During MMTT Efficacy Estimand at 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.	Baseline, Week 16
Secondary	Percentage of Time With Sensor Glucose Values Between 70 and 180 mg/dL Efficacy Estimand at 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).	Week 16
Secondary	Rate of Severe Hypoglycemia at 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.	Baseline through Week 16
Secondary	Rate of Documented Symptomatic Hypoglycemia at 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.	Baseline through Week 16
Secondary	Change From Baseline in 1,5-Anhydroglucitol (1,5-AG) at 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.	Baseline, Week 16
Secondary	Change From Baseline in 10-Point Self-Monitoring Blood Glucose (SMBG) Values at 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.	Baseline, Week 16
Secondary	Change From Baseline in Insulin Dose at 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.	Baseline, Week 16
Secondary	Change From Baseline in Bolus/Total Insulin Dose Ratio at 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.	Baseline, Week 16
Secondary	Percentage of Participants With HbA1c <7%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 16
Secondary	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 pump occlusion alarm that leads to an unplanned infusion set change was evaluated.	Baseline through Week 16
Secondary	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	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.	Baseline through Week 16

External Links

•   A Study Comparing LY900014 to Insulin Lispro in Adults With Type 1 Diabetes Using Insulin Pump Therapy