A Study Comparing LY900014 to Insulin Lispro (Humalog) in Children and Adolescents With Type 1 Diabetes

Phase 3

Completed

Conditions: Type 1 Diabetes Mellitus

Interventions: Drug: LY900014
Drug: Insulin Lispro
Drug: Insulin Glargine
Drug: Insulin Degludec

Registration Number: NCT03740919

Lead Sponsor: Eli Lilly and Company

Brief Summary: The reason for this study is to compare the study drug LY900014 to insulin lispro (Humalog) in children and adolescents with type 1 diabetes (T1D).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 751

Inclusion Criteria

T1D for at least 6 months at the screening visit.
Have been treated with only one of the following rapid-acting insulin analogs as part of an multiple daily injection regimen for at least the last 90 days prior to the screening visit:
- insulin lispro U-100, or
- insulin aspart
- insulin glulisine or
- fast acting insulin aspart
Have been treated with only one of the following basal insulins for at least the last 90 days prior to the screening visit:
- insulin glargine U-100 (once a day [QD] or twice a day [BID]), or
- insulin detemir U-100 (QD or BID), or
- insulin degludec U-100 (QD)
Have a HbA1c value ≤ 9.9% at the screening visit.

Exclusion Criteria

Have current hypoglycemic unawareness or have had more than 1 episode of severe hypoglycemia within 6 months prior to the screening visit.
Have had more than 1 emergency room visit or hospitalization due to poor glucose control within 6 months prior to the screening visit.
Have been on a treatment regimen that includes regular human insulin, neutral protamine Hagedorn (NPH), Afrezza® (insulin human) inhalation powder, any premixed insulins or use of diluted insulins within 90 days prior to the screening visit.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LY900014	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
LY900014 Postmeal	LY900014	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Insulin Lispro (Humalog)	Insulin Lispro	Participants received 100 units per milliliter (U/mL) insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.
Insulin Lispro (Humalog)	Insulin Glargine	Participants received 100 units per milliliter (U/mL) insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.
Insulin Lispro (Humalog)	Insulin Degludec	Participants received 100 units per milliliter (U/mL) insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26	Baseline, Week 26	Change from baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Documented Hypoglycemic Events	Baseline through Week 26	Documented hypoglycemia is defined as \<54 mg/dL and ≤70 mg/dL, respectively.
Change From Baseline in HbA1c (Postprandial) at Week 26	Baseline, Week 26	Change from baseline in HbA1c postprandial was analyzed using (MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.
Rate of Severe Hypoglycemia	Week 0 through Week 26	Severe hypoglycemia: during these episodes, participants have an altered mental status and cannot assist in their own care, may be semiconscious or unconscious, or experience coma with or without seizures, and require assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. The rate of severe hypoglycemia per 100 years was calculated as: 100 times the total number of severe hypoglycemia episodes within the period divided by total exposure (in year) for all participants within the treatment group.
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26	Baseline, Week 26	Change from baseline in 7-point SMBG values were analyzed using MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group, and HbA1c stratum (≤8.0%, \>8.0%)) baseline value, visit, and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors.
Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose	Baseline through Week 26	Documented post-dose hypoglycemia event is an event of blood glucose of \< 54 mg/dL and ≤70 mg/dL that occurred within 1 and 2 hours after the prandial dose. The rate of documented hypoglycemia was estimated by a negative binomial regression including treatment and age group as independent variable and number of episodes as dependent variables with log (exposure/365.25 days) as the offset in the model.
Change From Baseline in Insulin Dose at Week 26	Baseline, Week 26	Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, age group, and HbA1c stratum (≤8.0%, \>8.0%)), baseline value, visit and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors.
Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose	Baseline through Week 26	Documented post-dose hypoglycemia \<54 milligrams per deciliter (mg/dL) and ≤ 70 mg/dL that occurred 1 and 2 hours after prandial dose.
Rate of Documented Hypoglycemia Events	Week 0 through Week 26	Documented hypoglycemia is defined as a hypoglycemic event of blood glucose of ≤70 mg/dL or \<54 mg/dL. The rate of documented hypoglycemia was estimated by negative binomial regression including treatment and age group as independent variables and number of episodes as dependent variable with log (exposure/365.25 days) as the offset in the model.
Percentage of Participants With HbA1c < 7.0% and <7.5%	Week 26	Percentage of participants with HbA1c \< 7.0% and \<7.5% was analyzed using a longitudinal logistic regression with repeated measurements conducted by a generalized linear mixed model including independent variables of treatment, baseline HbA1c value, visit, baseline HbA1c-by-visit interaction, and treatment-by-visit interaction. An unstructured covariance structure was used.

Trial Locations

Locations (111): Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸
Idaho Falls, Idaho, United States
Children's Hospital Los Angeles - Dept of Endocrinology
🇺🇸
Los Angeles, California, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
Wuxi Children's Hospital
🇨🇳
Wuxi, Jiangsu, China
Azienda Ospedaliero Universitaria Meyer
🇮🇹
Firenze, Italy
Ospedale Civile Maggiore Borgo Trento
🇮🇹
Verona, Italy
Children's Hospital Capital Institute of Pediatrics
🇨🇳
Beijing, China
Medica Iberia
🇨🇿
Opava, Czechia
Zhengzhou Children's Hospital
🇨🇳
Zhengzhou, China
Niigata University Medical & Dental Hospital
🇯🇵
Niigata, Japan
Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽
Monterrey, N.l., Mexico
Tallahassee Memorial HealthCare
🇺🇸
Tallahassee, Florida, United States
Barry Reiner Clinic
🇺🇸
Baltimore, Maryland, United States
Fakultni Nemocnice v Motole
🇨🇿
Praha 5, Motole, Czechia
Hospital das Clinicas da FMRP
🇧🇷
Ribeirao Preto, SP, Brazil
RED-Institut GmbH
🇩🇪
Oldenburg in Holstein, Schleswig Holstein, Germany
CHU Hopital d'enfants de la Timone
🇫🇷
Marseille CEDEX 05, France
Hôpital Universitaire Necker enfants malades
🇫🇷
Paris, France
FN Ostrava
🇨🇿
Ostrava-Poruba, Czechia
CPCLIN
🇧🇷
São Paulo, SP, Brazil
CPQuali Pesquisa Clínica
🇧🇷
São Paulo, Brazil
Shamir Medical Center (Asaf Harofe)-Pediatric Endocrinology Unit
🇮🇱
Beer Yaakov, Israel
Children's hospital of Fudan University
🇨🇳
Shanghai, China
Herlev and Gentofte Hospital
🇩🇰
Herlev, Denmark
CHRU Lille - Hôpital Jeanne de Flandre
🇫🇷
Lille, France
Medizinisches Versorgungszentrum am Universitätsklinikum Leipzig GmbH
🇩🇪
Leipzig, Sachsen, Germany
Stanford University School of Medicine - Division of Pediatric Endocrinology & Diabetes
🇺🇸
Palo Alto, California, United States
Iowa Diabetes and Endocrinology Research Center
🇺🇸
West Des Moines, Iowa, United States
UBMD Pediatrics
🇺🇸
Buffalo, New York, United States
Children's hospital of Nanjing
🇨🇳
Nanjing, Jiangsu, China
InnoDiab Forschung Gmbh
🇩🇪
Essen, Nordrhein-Westfalen, Germany
The Fourth Affiliated Hospital of Harbin Medical University
🇨🇳
Harbin, Nangang District, China
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Pediatricke odd. Nemocnice Jihlava
🇨🇿
Jihlava, Czechia
Hospital Universitario HM Monteprincipe
🇪🇸
Boadilla del Monte, Spain
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Czechia
Ospedale Bambino Gesu
🇮🇹
Roma, Italy
Saitama Children's Medical Center
🇯🇵
Saitama-shi, Saitama, Japan
Instytut Diabetologii Sp. z o.o
🇵🇱
Warsaw, Poland
Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)
🇪🇸
Sevilla, Spain
Hospital Universitario Central de Asturias
🇪🇸
Oviedo, Asturias, Spain
Hospital Sant Joan de Déu
🇪🇸
Esplugues de Llobregat, Spain
Tver Children's Clinical Hospital
🇷🇺
Tver, Russian Federation
Hospital Virgen del Camino
🇪🇸
Pamplona, Navarra, Spain
Hospital Txagorritxu
🇪🇸
Vitoria-Gasteiz, Spain
VanMeter Pediatric Endocrinology, P.C.
🇺🇸
Atlanta, Georgia, United States
Joslin Diabetes Center
🇺🇸
Boston, Massachusetts, United States
Indiana University- Riley Children's Hospital
🇺🇸
Indianapolis, Indiana, United States
Rady Childrens Hospital - San Diego
🇺🇸
San Diego, California, United States
Pennington Biomedical Research Center
🇺🇸
Baton Rouge, Louisiana, United States
Voronezh State Medical University
🇷🇺
Voronezh, Russian Federation
Azienda Ospedaliera Universitaria Federico II
🇮🇹
Napoli, Italy
Suny Health Science Center at Syracuse
🇺🇸
Syracuse, New York, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Texas Institute for Kidney and Endocrine Disorders
🇺🇸
Lufkin, Texas, United States
Pardubicka krajska nemocnice
🇨🇿
Pardubice, Czechia
Diabetologische Schwerpunktpraxis Dr. Ziegler
🇩🇪
Münster, North Rhine-Westphalia, Germany
Azienda Ospedaliera Umberto I
🇮🇹
Ancona, Italy
IRCCS Ospedale San Raffaele
🇮🇹
Milano, Italy
Nihon University Hospital
🇯🇵
Chiyoda-ku, Tokyo, Japan
Smolensk Regional Children's Clinical Hospital
🇷🇺
Smolensk, Russian Federation
Research Institute for Pediatric Endocrinology
🇷🇺
Moscow, Russian Federation
Hospital Universitario La Fe de Valencia
🇪🇸
Valencia, Spain
Ivano-Frankivsk regional clinical children hospital
🇺🇦
Ivano-Frankivsk, Ukraine
Vinnytsia Regional Clinical Highly Specialized Endocrinology Center
🇺🇦
Vinnytsia, Ukraine
V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine
🇺🇦
Kyiv, Ukraine
Odesa regional children's clinical hospital
🇺🇦
Odesa, Ukraine
Stepping Hill Hospital
🇬🇧
Stockport, Cheshire, United Kingdom
Zaporizhzhia regional clinical children hospital
🇺🇦
Zaporizhzhia, Ukraine
Norfolk and Norwich Hospital
🇬🇧
Norwich, Norfolk, United Kingdom
King's Mill Hospital
🇬🇧
Sutton In Ashfield, Nottinghamshire, United Kingdom
Worthing Hospital
🇬🇧
Worthing, West Sessex, United Kingdom
St Richards Hospital
🇬🇧
Chichester, West Sussex, United Kingdom
St James's University Hospital
🇬🇧
Leeds, West Yorkshire, United Kingdom
St. George's University Hospitals NHS Foundation Trust
🇬🇧
London, United Kingdom
University of Alabama Birmingham
🇺🇸
Birmingham, Alabama, United States
Barbara Davis Center
🇺🇸
Aurora, Colorado, United States
University of South Florida Diabetes & Endocrinology Center
🇺🇸
Tampa, Florida, United States
Diabetes and Glandular Disease Research Associates PA
🇺🇸
San Antonio, Texas, United States
CHUS - Hospital Clinico Universitario
🇪🇸
La Coruña, Spain
Soroka Medical Center - Pediatric Outpatient Clinic
🇮🇱
Beer-Sheva, Israel
Osaka City University Hospital
🇯🇵
Osaka, Japan
Siberian State Medical University of Roszdrav
🇷🇺
Tomsk, Russian Federation
Tokyo Women's Medical University Hospital
🇯🇵
Shinjuku-ku, Tokyo, Japan
St. Luke's Children's Endocrinology
🇺🇸
Boise, Idaho, United States
Schneider Children's Medical Center
🇮🇱
Petah Tikva, Israel
Samarskiy Regional Children's Clinical Hospital
🇷🇺
Samara, Russian Federation
Centro de Inv. Medica de Occidente, SC
🇲🇽
Zapopan, Jalisco, Mexico
Cli-nica Hospital Cemain
🇲🇽
Tampico, Tamaulipas, Mexico
Endocrinology Services NorthWest
🇺🇸
Bend, Oregon, United States
Universitätsklinikum Graz
🇦🇹
Graz, Steiermark, Austria
Shiba Medical Center
🇮🇱
Ramat-gan, Israel
Hiroshima Prefectural Hospital
🇯🇵
Hiroshima, Japan
Hospital Angeles Puebla
🇲🇽
Puebla, Mexico
Gdanski Uniwersytet Medyczny
🇵🇱
Gdansk, Poland
Uniwersytecki Szpital Kliniczny
🇵🇱
Lodz, Poland
San Jorge Children and Women's Hospital- Shipping Location
🇵🇷
San Juan, Puerto Rico
Saratov State Medical University
🇷🇺
Saratov, Russian Federation
St.Petersburg Children's City Polyclinic #44
🇷🇺
St.Petersburg, Russian Federation
Institute of the Health Care of Children & Adolescents
🇺🇦
Kharkiv, Ukraine
Unidad de Investigacion Clinica Cardiometabolica de Occidente
🇲🇽
Guadalajara, Jalisco, Mexico
Rambam Medical Center - Department of Pediatrics A, Ruth Rappaport Children's Hospital
🇮🇱
Haifa, Israel
Pediatric Endocrine Research Associates
🇵🇷
Rio Piedras, Puerto Rico
Morozovsky Children's City Clinical Hospital
🇷🇺
Moscow, Russian Federation
Center of Excellence in Diabetes & Endocrinology
🇺🇸
Sacramento, California, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
Texas Diabetes & Endocrinology, P.A.
🇺🇸
Austin, Texas, United States
Children's Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
Universitätsklinik Innsbruck
🇦🇹
Innsbruck, Tyrol, Austria
MultiCare Institute for Research & Innovation
🇺🇸
Tacoma, Washington, United States
Hopital Robert Debre
🇫🇷
Paris, France