Clinical Trial Details
| Trial ID: | L5225 |
| Source ID: | NCT03429543 |
| Associated Drug: | Metformin |
| Title: | Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TM |
| Acronym: | |
| Status: | COMPLETED |
| Study Results: | YES |
| Results: | https://ClinicalTrials.gov/show/NCT03429543/results |
| Conditions: | Diabetes Mellitus, Type 2 |
| Interventions: | DRUG: Metformin|DRUG: Insulin|DRUG: Placebo|DRUG: Linagliptin|DRUG: Empagliflozin |
| Outcome Measures: | Primary: Change in Glycated Haemoglobin (HbA1c) (%) From Baseline to the End of 26 Weeks - DINAMOᵀᴹ, Adjusted means taken from the following three models, as pre-specified in the protocol: Treatment group 1 (TG1): \[Placebo\], \[Linagliptin 5mg\] and \[Empagliflozin pooled\] Treatment group 2 (TG2): \[Placebo\] and \[Empagliflozin 10mg and 10+25mg\] Treatment group 3 (TG3): \[Placebo\] and \[Empagliflozin 10mg\] ANCOVA with continuous covariate (baseline HbA1c) and categorical covariates (treatment \& age). Effect of linagliptin and of empagliflozin was compared with placebo at an overall α of 0.05 (2-sided) using the Hochberg method to account for multiple testing. After having obtained statistically significant results for both hypotheses of the primary family of hypotheses (TG1), the secondary hypotheses were to compare the individual empagliflozin doses versus placebo (TG2 \& TG3). ANCOVA utilized a weight of zero for patients who were not in the hypothesis test of interest, a value of 2 for re-randomised patients who were in the hypothesis test of interest and a value of 1 otherwise., Baseline (Day 1) and week 26 of treatment.|Percentage of Patients With Treatment Failure up to or at Week 26, Percentage of patients with treatment failure up to or at Week 26 as a binary endpoint, defined as meeting at least one of the following criteria: * Use of rescue medication at any time up to Week 26 * Increase from baseline in HbA1c by 0.5% at Week 26 . Increase from baseline in HbA1c to above 7.0% at Week 26 in patients with baseline HbA1c \<7.0%, Up to 26 weeks. | Secondary: Change in HbA1c (%) From Baseline to the End of 26 Weeks - DINAMOᵀᴹ Mono, Change in Glycated haemoglobin (HbA1c) (%) from baseline to the end of 26 weeks. Adjusted values came from a restricted maximum likelihood (REML) approach with mixed model for repeated measures (MMRM). Analyses included fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the categorical covariate age at randomisation and the continuous, fixed covariates of baseline of the response variable and baseline of the response variable-by-visit interaction. The covariate visit was treated as the repeated measure with an unstructured covariance structure used to model the within-patient measurements., Baseline (Day 1) and week 26 of treatment.|Time to Treatment Failure, Time to treatment failure was analysed by Kaplan-Meier estimates up to the end of the study (Week 52). Patients in the placebo group were censored after 26 weeks unless a prior treatment failure was observed., Up to 395 days.|Change in Fasting Plasma Glucose (FPG, mg/dL) From Baseline to the End of 26 Weeks, Change in fasting plasma glucose (FPG, Milligrams Per Deciliter (mg/dL)) from baseline to the end of 26 weeks. Adjusted values taken from analysis of covariance (ANCOVA) model with treatment as a fixed classification effect, baseline FPG as linear covariate and age at randomisation as categorical covariate. The random error was assumed to be normally distributed., Baseline (Day 1) and week 26.|Change in Body Weight (kg) From Baseline to the End of 26 Weeks, Change in body weight (kg) from baseline to the end of 26 weeks. Adjusted values taken from mixed model for repeated measures (MMRM) with the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the categorical covariate age at randomisation and the continuous, fixed covariates of baseline of the response variable and baseline of the response variable-by-visit interaction. The covariate visit was treated as repeated measure with an unstructured covariance structure used to model the within-patient measurements., Baseline (Day 1) and week 26.|Change in Systolic Blood Pressure (SBP, mmHg) From Baseline to the End of 26 Weeks, Change in systolic blood pressure (SBP, millimeters of mercury (mmHg)) from baseline to the end of 26 weeks. Adjusted values taken from mixed model for repeated measures (MMRM) with the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the categorical covariate age at randomisation and the continuous, fixed covariates of baseline of the response variable and baseline of the response variable-by-visit interaction. The covariate visit was treated as repeated measure with an unstructured covariance structure used to model the within-patient measurements., Baseline (Day 1) and week 26.|Change in Diastolic Blood Pressure (DBP, mmHg) From Baseline to the End of 26 Weeks, Change in diastolic blood pressure (DBP, millimeters of mercury (mmHg)) from baseline to the end of 26 weeks. Adjusted values taken from mixed model for repeated measures (MMRM) with the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the categorical covariate age at randomisation and the continuous, fixed covariates of baseline of the response variable and baseline of the response variable-by-visit interaction. The covariate visit was treated as repeated measure with an unstructured covariance structure used to model the within-patient measurements., Baseline (Day 1) and week 26.|Percentage of Patients Who Achieve HbA1c <6.5% at the End of 26 Weeks, Percentage of patients who achieve HbA1c \<6.5% at the end of 26 weeks., Baseline (Day 1) and week 26.|Percentage of Patients Who Achieve HbA1c <7.0% at the End of 26 Weeks, Percentage of patients who achieve HbA1c \<7.0% at the end of 26 weeks., Baseline (Day 1) and week 26. |
| Sponsor/Collaborators: | Sponsor: Boehringer Ingelheim |
| Gender: | ALL |
| Age: | CHILD |
| Phases: | PHASE3 |
| Enrollment: | 175 |
| Study Type: | INTERVENTIONAL |
| Study Designs: | Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT |
| Start Date: | 2018-03-20 |
| Completion Date: | 2023-05-31 |
| Results First Posted: | 2024-02-23 |
| Last Update Posted: | 2024-02-23 |
| Locations: | Phoenix Children's Hospital, Phoenix, Arizona, 85016, United States|University of Arizona, Tucson, Arizona, 85724, United States|CHOC Children's Hospital, Orange, California, 92868, United States|Stanford University Medical Center, Palo Alto, California, 94304, United States|Rady Children's Hospital - San Diego, San Diego, California, 92123, United States|University of California San Francisco, San Francisco, California, 94158, United States|Children's Hospital Colorado, Aurora, Colorado, 80045, United States|Yale University School of Medicine, New Haven, Connecticut, 06511, United States|Empire Clinical Research, LLC, Miami Lakes, Florida, 33016, United States|Oceane7 Clinical Research, Miami, Florida, 33144, United States|Pediatric and Adult Research Center, Orlando, Florida, 32825, United States|Nemours Clinic, Pensacola, Florida, 32514, United States|University of South Florida, Tampa, Florida, 33612, United States|AdventHealth Medical Group, Pediatric Diabetes and Endocrinology at Winter Park, Winter Park, Florida, 32789, United States|Children's Center for Advanced Pediatrics, Atlanta, Georgia, 30329, United States|Atlanta Center, Atlanta, Georgia, 30331, United States|Columbus Regional Research Institute, Columbus, Georgia, 31904, United States|Rocky Mountain Diabetes and Osteoporosis Center, Idaho Falls, Idaho, 83404, United States|University of Iowa Hospitals and Clinics, Iowa City, Iowa, 52242, United States|Novak Center for Children's Health, Louisville, Kentucky, 40202, United States|Johns Hopkins Hospital, Baltimore, Maryland, 21287, United States|Boston Children's Hospital, Boston, Massachusetts, 02115, United States|Joslin Diabetes Center, Boston, Massachusetts, 02215, United States|Integrative Biosciences Center, Detroit, Michigan, 48202, United States|University Of Mississippi Medical Center, Jackson, Mississippi, 39216-4505, United States|Children's Mercy Hospitals and Clinics, Kansas City, Missouri, 64108, United States|Advantage Clinical Trials, Bronx, New York, 10468, United States|UBMD Pediatrics, Buffalo, New York, 14203, United States|New York University Langone Medical Center, New York, New York, 10016, United States|SUNY Upstate Medical University, Syracuse, New York, 13210, United States|The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27514, United States|University Hospitals of Cleveland, Cleveland, Ohio, 44106, United States|University of Oklahoma, Oklahoma City, Oklahoma, 73104, United States|University of Oklahoma, Tulsa, Oklahoma, 74135, United States|Penn State College of Medicine, Hershey, Pennsylvania, 17033, United States|Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, United States|Monument Health Rapid City Hospital, Inc., Rapid City, South Dakota, 57701, United States|LifeDoc Research, PLLC, Memphis, Tennessee, 38119, United States|Vanderbilt University Medical Center, Nashville, Tennessee, 37232, United States|Office of Amir A. Hassan, MD, P.A., Houston, Texas, 77089, United States|Saenz Medical Center, La Joya, Texas, 78560, United States|Texas Diabetes Institute, San Antonio, Texas, 78207, United States|University of Virginia Health System, Charlottesville, Virginia, 22908, United States|Children's Hospital of Richmond at VCU, Richmond, Virginia, 23219, United States|Sanatorio Allende S.A., Nueva Córdoba, X5000JHQ, Argentina|Hospital de Clínicas Pte. Dr. Nicolás Avellaneda, San Miguel de Tucumán, 4000, Argentina|Instituto de Estudos e Pesquisas Clínicas IEP-CE, Fortaleza, 60160-230, Brazil|Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, 14048-900, Brazil|University of Manitoba - Health Sciences Centre, Winnipeg, Manitoba, R3E 3P4, Canada|The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada|The First Hospital of Jilin University, Changchun, 130021, China|Zhengzhou Children'S Hospital, Zhengzhou, 450017, China|Centro de Diabetes Cardiovascular IPS, Barranquilla, 80020, Colombia|Dexa-Diab IPS, Bogotá DC, 110221, Colombia|Universitätsklinikum Freiburg, Freiburg, 79106, Germany|Soroka Univ. Medical Center, Beer Sheva, 84101, Israel|Rambam Medical Center, Haifa, 31096, Israel|The Chaim Sheba Medical Center Tel HaShomer, Ramat-Gan, 5265601, Israel|Severance Hospital, Seoul, 03722, Korea, Republic of|Asan Medical Center, Seoul, 05505, Korea, Republic of|Ajou University Hospital, Suwon, 16499, Korea, Republic of|Investigación en Salud y Metabolismo S.C., Chihuahua, 31217, Mexico|CAIMED Investigacion en Salud, S.A. de C.V., Ciudad de México, 06760, Mexico|Centro de Estudios de Investigación Metabólicos y Cardiovasculares, S.C., Ciudad Madero, 89440, Mexico|Consultorio Medico, Puebla, 72190, Mexico|Investigacion Medica Sonora S.C., Sonora, 83280, Mexico|Centro de Investigación Médica de Ocidente, S.C., Zapopan, 45116, Mexico|San Juan Bautista School of Medicine, Caguas, 00726, Puerto Rico|Regional Clinical Hospital 'The Badge of Honor Order', Irkutsk, 664049, Russian Federation|Ivanovo Reg.Clin.Hosp., Ivanovo, 153040, Russian Federation|Rep.childrens clin.hosp., Izhevsk, 426009, Russian Federation|State Medical University, Kazan, Kazan, 420012, Russian Federation|Munic. Instit. of HC "Kirov clin. hosp.#7 n.a.V.I.Urlova", Kirov, 610014, Russian Federation|Endocrinology Scientific Center, MoH and Social Development, Moscow, 117036, Russian Federation|State Novosibirsk Regional Clinical Hospital, Novosibirsk, 630091, Russian Federation|Fed. State Budget Educational Instit. of Higher Education "Rostov State Med. Univ." of MoH of RF, Rostov-on-Don, 344022, Russian Federation|St. Petersburg State Pediatric University, St. Petersburg, 194100, Russian Federation|Siberian State Med.Uni,Faculty Therapy Dep.w/ Clin.Pharmacol, Tomsk, 634050, Russian Federation|Bahkir state med. Univ. of the Ministry Polyclinic Pediatric, Ufa, 450106, Russian Federation|Srinagarind Hospital, Khon Kaen, 40002, Thailand|Rajavithi Hospital, Krung Thep Maha Nakhon, 10400, Thailand|St George's Hospital, London, SW17 0QT, United Kingdom|Royal Berkshire Hospital, Reading, RG1 5AN, United Kingdom |
| URL: | https://clinicaltrials.gov/show/NCT03429543 |
