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

Type 1 Diabetes Mellitus Clinical Trial

— PRONTO-Peds  

Official title:

A Prospective, Randomized, Double-Blind Comparison of LY900014 to Humalog With an Open-Label Postprandial LY900014 Treatment Group in Children and Adolescents With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03740919
• Other study ID #: 16698
• Secondary ID: I8B-MC-ITSB2018-
• Status: Completed
• Phase: Phase 3
• Start date: April 7, 2019
• Est. completion date: July 2, 2021

Study information

• Verified date: December 2021
• 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) in children and adolescents with type 1 diabetes (T1D).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 751
• Est. completion date: July 2, 2021
• Est. primary completion date: July 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• LY900014
Administered SC
• Insulin Lispro
Administered SC
• Insulin Glargine
Administered SC
• Insulin Degludec
Administered SC

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  China,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at 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.	Baseline, Week 26
Secondary	Change From Baseline in HbA1c (Postprandial) at 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.	Baseline, Week 26
Secondary	Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose	Documented post-dose hypoglycemia <54 milligrams per deciliter (mg/dL) and = 70 mg/dL that occurred 1 and 2 hours after prandial dose.	Baseline through Week 26
Secondary	Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose	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.	Baseline through Week 26
Secondary	Percentage of Participants With Documented Hypoglycemic Events	Documented hypoglycemia is defined as <54 mg/dL and =70 mg/dL, respectively.	Baseline through Week 26
Secondary	Rate of Documented Hypoglycemia Events	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.	Week 0 through Week 26
Secondary	Rate of Severe Hypoglycemia	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.	Week 0 through Week 26
Secondary	Change From Baseline in Insulin Dose at 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.	Baseline, Week 26
Secondary	Percentage of Participants With HbA1c < 7.0% and <7.5%	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.	Week 26
Secondary	Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at 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.	Baseline, Week 26

External Links

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