Ertugliflozin Type 2 Diabetes Mellitus (T2DM) Pediatric Study (MK-8835/PF-04971729) (MK-8835-059)

NCT ID: NCT04029480

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-08
• Study Completion Date: 2025-04-11

Brief Summary

This study evaluated the safety and efficacy of ertugliflozin (MK-8835) in pediatric participants with T2DM on metformin with/without insulin. The primary hypothesis of the study was that the addition of ertugliflozin reduces hemoglobin A1C (HbA1C) more than the addition of placebo after 24 weeks of treatment.

Detailed Description

Participants were randomized on Day 1 to the following arms:

• 5 mg ERTU and placebo to 15 mg ERTU (5 mg Ertugliflozin)
• placebo to 5 mg ERTU and placebo to 15 mg ERTU (Placebo)

At Week 12, participants who met the up-titration criteria were re-randomized to the following arms for Weeks 12 to 54:

• 5 mg ERTU and placebo to 15 mg ERTU (5 mg/5 mg Ertugliflozin)
• 15 mg ERTU and placebo to 5 mg ERTU (5 mg/15 mg Ertugliflozin) Participants who did not meet the up-titration criteria remained on 5 mg ERTU and placebo to 15 mg ERTU from Week 12 to Week 54.

The placebo arm continued receiving placebo from Week 12 to Week 54.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ertugliflozin 5 mg

All participants initially received 5 mg ertugliflozin (ERTU) once daily (QD) and placebo to 15 mg ERTU QD until Week 54 (WK54). At Week 12 (WK12), participants who did not meet the up-titration criteria remained on 5 mg ERTU and placebo to 15 mg ERTU. Participants remained on their background metformin with/without insulin treatment throughout the study.

Group Type: EXPERIMENTAL

Ertugliflozin 5 mg

Intervention Type: DRUG

Ertugliflozin 5 mg, oral, 1 tablet QD

Placebo to ertugliflozin 15 mg

Intervention Type: DRUG

Placebo to ertugliflozin 15 mg, oral, 1 tablet QD

Insulin

Intervention Type: BIOLOGICAL

Participants on insulin at screening continued to receive a stable dose of background insulin. The initiation and titration of insulin for rescue therapy was at the discretion of the investigator, based on local/regional/country guidelines.

Metformin

Intervention Type: DRUG

Participants received stable dose of background metformin.

Ertugliflozin 5 mg/5 mg

All participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until Week 12. Participants remained on their background metformin with/without insulin treatment throughout the study. Participants who met the up-titration criteria at the WK12 second randomization were re-randomized to remain on 5 mg ERTU and placebo to 15 mg ERTU from WK12 to WK54.

Group Type: EXPERIMENTAL

Ertugliflozin 5 mg

Intervention Type: DRUG

Ertugliflozin 5 mg, oral, 1 tablet QD

Placebo to ertugliflozin 15 mg

Intervention Type: DRUG

Placebo to ertugliflozin 15 mg, oral, 1 tablet QD

Insulin

Intervention Type: BIOLOGICAL

Participants on insulin at screening continued to receive a stable dose of background insulin. The initiation and titration of insulin for rescue therapy was at the discretion of the investigator, based on local/regional/country guidelines.

Metformin

Intervention Type: DRUG

Participants received stable dose of background metformin.

Ertugliflozin 5 mg/15 mg

All participants initially received 5 mg ERTU QD and placebo to 15 mg ERTU QD until Week 12. Participants remained on their background metformin with/without insulin treatment throughout the study. Participants who met the up-titration criteria at the WK12 second randomization were up-titrated to 15 mg ERTU and placebo to 5 mg ERTU from WK12 to WK54.

Group Type: EXPERIMENTAL

Ertugliflozin 5 mg

Intervention Type: DRUG

Ertugliflozin 5 mg, oral, 1 tablet QD

Ertugliflozin 15 mg

Intervention Type: DRUG

Ertugliflozin 15 mg, oral, 1 tablet QD

Placebo to ertugliflozin 15 mg

Intervention Type: DRUG

Placebo to ertugliflozin 15 mg, oral, 1 tablet QD

Placebo to ertugliflozin 5 mg

Intervention Type: DRUG

Placebo to ertugliflozin 5 mg, oral, 1 tablet QD

Insulin

Intervention Type: BIOLOGICAL

Participants on insulin at screening continued to receive a stable dose of background insulin. The initiation and titration of insulin for rescue therapy was at the discretion of the investigator, based on local/regional/country guidelines.

Metformin

Intervention Type: DRUG

Participants received stable dose of background metformin.

Placebo

All participants received matched placebo to 5 mg ERTU and 15 mg ERTU from baseline to WK54. Participants remained on their background metformin with/without insulin treatment throughout the study.

Group Type: PLACEBO_COMPARATOR

Placebo to ertugliflozin 15 mg

Intervention Type: DRUG

Placebo to ertugliflozin 15 mg, oral, 1 tablet QD

Placebo to ertugliflozin 5 mg

Intervention Type: DRUG

Placebo to ertugliflozin 5 mg, oral, 1 tablet QD

Insulin

Intervention Type: BIOLOGICAL

Participants on insulin at screening continued to receive a stable dose of background insulin. The initiation and titration of insulin for rescue therapy was at the discretion of the investigator, based on local/regional/country guidelines.

Metformin

Intervention Type: DRUG

Participants received stable dose of background metformin.

Interventions

Ertugliflozin 5 mg

Ertugliflozin 5 mg, oral, 1 tablet QD

Intervention Type: DRUG

Ertugliflozin 15 mg

Ertugliflozin 15 mg, oral, 1 tablet QD

Intervention Type: DRUG

Placebo to ertugliflozin 15 mg

Placebo to ertugliflozin 15 mg, oral, 1 tablet QD

Intervention Type: DRUG

Placebo to ertugliflozin 5 mg

Placebo to ertugliflozin 5 mg, oral, 1 tablet QD

Intervention Type: DRUG

Insulin

Participants on insulin at screening continued to receive a stable dose of background insulin. The initiation and titration of insulin for rescue therapy was at the discretion of the investigator, based on local/regional/country guidelines.

Intervention Type: BIOLOGICAL

Metformin

Participants received stable dose of background metformin.

Intervention Type: DRUG

Other Intervention Names

MK-8835; PF-04971729; MK-8835; PF-04971729

Eligibility Criteria

Inclusion Criteria

• Be ≥10 years and ≤17 years of age, when the informed consent is signed
• Has diabetes diagnosed by one of the American Diabetes Association (ADA) criteria.
• Has body mass index (BMI) ≥85th percentile at screening OR participant has a history of being overweight or obese at time of diagnosis of Type 2 diabetes mellitus (T2DM).
• T2DM for ≥2 years, OR T2DM for <2 years and a fasting C-peptide value >0.6 ng/mL at Screening.
• On stable metformin monotherapy (≥1500 mg/day, for ≥8 weeks prior to Screening, OR on a stable metformin dose (≥1500 mg/day, for ≥8 weeks prior to Screening and a stable dose of insulin for ≥8 weeks prior to Screening.
• Contraceptive use by male participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Is a non-sterilized female who is currently not sexually active OR who agrees to abstain from heterosexual activity OR who agrees to start contraception prior to initiating sexual activity and who agrees to use an adequate method of contraception. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Have a family member or adult who, along with the participant, will be closely involved in the participant's daily activities (in the opinion of the investigator) and in the participant's treatment and study procedures.

Exclusion Criteria

• Has known type 1 diabetes mellitus or documented evidence of positive diabetes autoantibodies performed when participant was diagnosed with diabetes.
• Has known monogenic diabetes, or secondary diabetes.
• Has symptomatic hyperglycemia and/or moderate to large ketonuria requiring immediate initiation of another antihyperglycemic agent, including insulin.
• Has a known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2) inhibitor.
• Is pregnant, or breast feeding or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study medication.
• Has previously taken an SGLT2 inhibitor (such as canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) or was enrolled in a study for these agents.
• Has a history of idiopathic acute pancreatitis or chronic pancreatitis.
• Has a history of severe hypoglycemia while on insulin.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

The University of Alabama at Birmingham ( Site 2207)

Birmingham, Alabama, United States

Children's Hospital - Los Angeles ( Site 2201)

Los Angeles, California, United States

Center of Excellence in Diabetes and Endocrinology ( Site 2203)

Sacramento, California, United States

Memorial Regional Hospital-Joe DiMaggio Children's Hospital Division of Pediatric Endocrinology ( Si

Hollywood, Florida, United States

ICCT Research International, Inc. ( Site 2211)

Chicago, Illinois, United States

Barry J. Reiner MD LLC ( Site 2204)

Baltimore, Maryland, United States

William Beaumont Hospital ( Site 2219)

Royal Oak, Michigan, United States

CHEAR Center LLC ( Site 2200)

The Bronx, New York, United States

Coastal Children''s Services ( Site 2202)

Wilmington, North Carolina, United States

The Children's Hospital of Philadelphia ( Site 2205)

Philadelphia, Pennsylvania, United States

Southern Endocrinology and Associates PA ( Site 2218)

Mesquite, Texas, United States

Cliniques Universitaires Saint-Luc ( Site 2300)

Brussels, Bruxelles-Capitale, Region de, Belgium

London Health Sciences Centre ( Site 0002)

London, Ontario, Canada

Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0001)

Montreal, Quebec, Canada

Centro De Diabetes Cardiovascular IPS Ltda ( Site 0101)

Barranquilla, Atlántico, Colombia

MedPlus Medicina Prepagada S.A. ( Site 0102)

Bogotá, Bogota D.C., Colombia

Clinica Los Yoses ( Site 0200)

San José, , Costa Rica

Hospital Infantil Dr. Robert Reid Cabral ( Site 0300)

Santo Domingo, Nacional, Dominican Republic

CHU du BOCAGE ( Site 0407)

Dijon, Cote-d Or, France

CHU Amiens Hopital Sud ( Site 0413)

Amiens, Picardie, France

Consultorio Privado Dr. Geraldine Utrilla ( Site 0501)

Chiquimula, , Guatemala

Endopedia ( Site 0503)

Guatemala City, , Guatemala

Private Practice - Dr. Flor de Maria Ranchos Monterroso ( Site 0502)

Guatemala City, , Guatemala

Pecsi Tudomanyegyetem Klinikai Kozpont Gyermekgyogyaszati Klinika ( Site 0708)

Pécs, Baranya, Hungary

Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház-Gyermekosztály ( Site 0705)

Békéscsaba, Bekescsaba, Hungary

Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0701)

Miskolc, Borsod-Abauj Zemplen county, Hungary

Vita Verum Medical Egeszsegugyi Szolgaltato Bt ( Site 0706)

Székesfehérvár, Fejér, Hungary

Petz Aladar Megyei Oktato Korhaz ( Site 0709)

Győr, Győr-Moson-Sopron, Hungary

Szabolcs Szatmár Bereg Vármegyei Oktatókórház ( Site 0704)

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0702)

Budapest, , Hungary

Semmelweis Egyetem II. sz. Gyermekgyogyaszati Klinika ( Site 0703)

Budapest, , Hungary

Soroka University Medical Center ( Site 0802)

Beersheba, , Israel

Armon M.C ( Site 0803)

Haifa, , Israel

Rambam Medical Center ( Site 0801)

Haifa, , Israel

Hadassah Mount Scopus ( Site 0800)

Jerusalem, , Israel

The Edmond and Lily Safra Children s Hospital ( Site 0804)

Ramat Gan, , Israel

A.O.Universitaria Meyer ( Site 0901)

Florence, Tuscany, Italy

U.O. di Diabetologia dell'Eta Evolutiva - AUSL 2 ( Site 0904)

Caltanissetta, , Italy

IRCCS G. Gaslini ( Site 0900)

Genova, , Italy

AOU Federico II di Napoli ( Site 0902)

Napoli, , Italy

IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0903)

Roma, , Italy

Ospedale Regina Margherita ( Site 0905)

Torino, , Italy

Hospital Universiti Sains Malaysia ( Site 1102)

Kubang Kerian, Kelantan, Malaysia

Hospital Taiping ( Site 1104)

Taiping, Perak, Malaysia

Hospital Pulau Pinang. ( Site 1101)

George Town, Pulau Pinang, Malaysia

Hospital Putrajaya ( Site 1103)

Putrajaya, Putrajaya, Malaysia

University Malaya Medical Centre ( Site 1100)

Kuala Lumpur, , Malaysia

Life Nova+ ( Site 1203)

Forbach, Pamplemousses District, Mauritius

Wellkin Hospital ( Site 1200)

Moka, , Mauritius

Unidad de Investigacion Clinica Cardiometabolica de Occidente ( Site 1007)

Guadalajara, Jalisco, Mexico

Centro de Investigacion Medica de Occidente S.C. ( Site 1001)

Guadalajara, Jalisco, Mexico

CAIMED Investigación en Salud S.A de C.V ( Site 1008)

Mexico City, Mexico City, Mexico

Bio Investigación AMARC, S.C. ( Site 1006)

Mexico City, Mexico City, Mexico

Unidad Biomedica Avanzada Monterrey S. A. ( Site 1005)

Monterrey, Nuevo León, Mexico

Unidad de Medicina Especializada SMA ( Site 1004)

San Juan del Río, Querétaro, Mexico

Consultorio Medico de Endocrinologia Pediatrica ( Site 1002)

Culiacán, Sinaloa, Mexico

Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 1003)

Madero, Tamaulipas, Mexico

Centro de Investigacion Medica Aguascalientes ( Site 1000)

Aguascalientes, , Mexico

Centro de Atencion e Investigacion Clinica SC ( Site 1009)

Aguascalientes, , Mexico

Davao Doctors Hospital ( Site 1400)

Davao City, Davao Del Sur, Philippines

Institute for Studies on Diabetes Foundation Inc. ( Site 1402)

Marikina City, National Capital Region, Philippines

West Visayas State University Medical Center ( Site 1401)

Iloilo City, , Philippines

IN VIVO ( Site 1501)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Poradnia Chorob Metabolicznych. Centrum Zdrowia Tuchow ( Site 1500)

Wierzchosławice, Lesser Poland Voivodeship, Poland

Instytut Diabetologii Sp z o o ( Site 1512)

Warsaw, Masovian Voivodeship, Poland

Clinical Medical Research Sp. z o.o. ( Site 1511)

Katowice, Silesian Voivodeship, Poland

Bashkir State Medical University Hospital ( Site 1603)

Ufa, Baskortostan, Respublika, Russia

Federal State Budget Institution Endocrinological Research Center ( Site 1611)

Moscow, Moscow, Russia

Children's City Clinical Hospital #1 ( Site 1604)

Novosibirsk, Novosibirsk Oblast, Russia

Rostov Scientific Research Institution of Obstetrics and Pediatry ( Site 1606)

Rostov-on-Don, Rostov Oblast, Russia

Samara City Pediatric Clinical Hospital n.a. N.N. Ivanova ( Site 1610)

Samara, Samara Oblast, Russia

St.Petersburg State Pediatric Medical University ( Site 1600)

Saint Petersburg, Sankt-Peterburg, Russia

Kazan State Medical University ( Site 1601)

Kazan', Tatarstan, Respublika, Russia

Siberian State Medical University ( Site 1602)

Tomsk, Tomsk Oblast, Russia

Voronezh State Medical University named after N.N.Burdenko ( Site 1608)

Voronezh, Voronezskaja Oblast, Russia

Hera General Hospital ( Site 1725)

Mecca, Al Bahah Region, Saudi Arabia

King Abdul Aziz Medical City. National Guard Health Affairs ( Site 1715)

Jeddah, Makkah Al Mukarramah, Saudi Arabia

King Abdulaziz Medical City - Al Ahsa ( Site 1730)

Al Ahsa, Riyadh Region, Saudi Arabia

King Abdul Aziz Medical City - AlRiyadh ( Site 1700)

Riyadh, Riyadh Region, Saudi Arabia

King Abdul Aziz Medical City - AlRiyadh ( Site 1705)

Riyadh, Riyadh Region, Saudi Arabia

King Salman bin Abdulaziz hospital - Al Riyadh ( Site 1720)

Riyadh, Riyadh Region, Saudi Arabia

King Salman bin Abdulaziz hospital Al Riyadh ( Site 1710)

Riyadh, Riyadh Region, Saudi Arabia

I. U. Cerrahpasa Tip Fakultesi ( Site 2406)

Istanbul, Istanbul, Turkey (Türkiye)

Cukurova Uni. Tip Fakultesi ( Site 2403)

Adana, , Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi-Çocuk Hastanesi, Çocuk Endokrinoloji ( Site 2407)

Ankara, , Turkey (Türkiye)

Marmara Üniversitesi Prof. Dr. Asaf Ataseven Hospital ( Site 2400)

Istanbul, , Turkey (Türkiye)

Chernivtsi Regional Children Clinical Hospital No. 1-Department of Pediatrics and Medical Genetics (

Chernivtsi, Chernivetska Oblast, Ukraine

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1914)

Dnipro, Dnipropetrovsk Oblast, Ukraine

MHI Regional Childrens Clinical Hospital ( Site 1908)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Institute of Children and Adolescents Health Care of the Academy of Medical Sciences ( Site 1915)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Ukr Center of Endocrine Surgery and Transplatation MOH Ukraine ( Site 1903)

Kyiv, Kyivska Oblast, Ukraine

Medical Center Verum ( Site 1913)

Kyiv, Kyivska Oblast, Ukraine

Institute of Endocrinology and Metabolism n.a. Komissarenko ( Site 1905)

Kyiv, Kyivska Oblast, Ukraine

Odessa Regional Children Clinical Hospital ( Site 1912)

Odesa, Odesa Oblast, Ukraine

Vinnitsa Regional Endocrinology Dispensary, VNMU n.a. M.I.Pyrogov ( Site 1901)

Vinnytsia, Vinnytsia Oblast, Ukraine

Dubai Diabetes Center ( Site 2002)

Dubai, Dubayy, United Arab Emirates

Mustafa Al Qaysi Medical Centre ( Site 2010)

Dubai, Dubayy, United Arab Emirates

Mediclinic City Hospital ( Site 2005)

Dubai, Dubayy, United Arab Emirates

Al Jalila Children s Specialty Hospital ( Site 2004)

Dubai, Dubayy, United Arab Emirates

Thumbay University Hospital ( Site 2001)

Ajman, , United Arab Emirates

Rashid Center For Diabetes and Research ( Site 2006)

Ajman, , United Arab Emirates

Royal London Hospital (Whitechapel) ( Site 2100)

London, London, City of, United Kingdom

Chelsea and Westminster Hospital ( Site 2103)

London, London, City of, United Kingdom

West Middlesex University Hospital ( Site 2104)

London, London, City of, United Kingdom

Countries

United States; Belgium; Canada; Colombia; Costa Rica; Dominican Republic; France; Guatemala; Hungary; Israel; Italy; Malaysia; Mauritius; Mexico; Philippines; Poland; Russia; Saudi Arabia; Turkey (Türkiye); Ukraine; United Arab Emirates; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://msd.trialsummaries.com/Study/StudyDetails?id=26199&tenant=MT_MSD_9011

Plain Language Summary

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

PHRR190913-002184

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-501085-21-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1279-3984

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-8835-059

Identifier Type: OTHER

Identifier Source: secondary_id

2017-003455-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8835-059

Identifier Type: -

Identifier Source: org_study_id