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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Study to Evaluate the Safety and Efficacy of Ertugliflozin (MK-8835/PF-04971729) in Pediatric Participants (Ages 10 to 17 Years, Inclusive) With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04029480
• Other study ID #: 8835-059
• Secondary ID: MK-8859-059PHRR1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 8, 2019
• Est. completion date: April 23, 2025

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 165
• Est. completion date: April 23, 2025
• Est. primary completion date: April 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Has diabetes diagnosed by one of the American Diabetes Association (ADA) criteria.

2. 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).

3. T2DM for =2 years, OR T2DM for <2 years and a fasting C-peptide value >0.6 ng/mL at Screening.

4. 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.

5. Contraceptive use by male participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

6. 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.

7. 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:

1. Has known type 1 diabetes mellitus or documented evidence of positive diabetes autoantibodies performed when participant was diagnosed with diabetes.

2. Has known monogenic diabetes, or secondary diabetes.

3. Has symptomatic hyperglycemia and/or moderate to large ketonuria requiring immediate initiation of another antihyperglycemic agent, including insulin.

4. Has a known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2) inhibitor.

5. 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.

6. Has previously taken an SGLT2 inhibitor (such as canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) or was enrolled in a study for these agents.

7. Has a history of idiopathic acute pancreatitis or chronic pancreatitis.

8. Has a history of severe hypoglycemia while on insulin.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Ertugliflozin 5 mg
Ertugliflozin 5 mg, oral, 1 tablet QD
• Ertugliflozin 15 mg
Ertugliflozin 15 mg, oral, 1 tablet QD
• Placebo to ertugliflozin 15 mg
Placebo to ertugliflozin 15 mg, oral, 1 tablet QD
• Placebo to ertugliflozin 5 mg
Placebo to ertugliflozin 5 mg, oral, 1 tablet QD

Biological:
• Insulin
The initiation and titration of insulin will be at the discretion of the investigator, based on local/regional/country guidelines.

Drug:
• Metformin
Participants will receive stable dose of background metformin.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc ( Site 2300)	Brussels	Bruxelles-Capitale, Region De
Canada	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
Colombia	Centro De Diabetes Cardiovascular IPS Ltda ( Site 0101)	Barranquilla	Atlantico
Colombia	MedPlus Medicina Prepagada S.A. ( Site 0102)	Bogota	Distrito Capital De Bogota
Costa Rica	Clinica Los Yoses ( Site 0200)	San Jose
Dominican Republic	Hospital Infantil Dr. Robert Reid Cabral ( Site 0300)	Santo Domingo	Distrito Nacional
France	CHU Amiens Hopital Sud ( Site 0413)	Amiens	Picardie
France	CHU du BOCAGE ( Site 0407)	Dijon	Cote-d Or
Guatemala	Consultorio Privado Dr. Geraldine Utrilla ( Site 0501)	Chiquimula
Guatemala	Endopedia ( Site 0503)	Guatemala
Guatemala	Private Practice - Dr. Flor de Maria Ranchos Monterroso ( Site 0502)	Guatemala City
Hungary	Békés Megyei Központi Kórház Dr. Réthy Pál Tagkórház-Gyermekosztály ( Site 0705)	Békéscsaba	Bekescsaba
Hungary	Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0702)	Budapest
Hungary	Semmelweis Egyetem II. sz. Gyermekgyogyaszati Klinika ( Site 0703)	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 0709)	Gyor	Gyor-Moson-Sopron
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0701)	Miskolc	Borsod-Abauj-Zemplen
Hungary	Szabolcs Szatmár Bereg Vármegyei Oktatókórház ( Site 0704)	Nyiregyhaza	Szabolcs-Szatmar-Bereg
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont Gyermekgyogyaszati Klinika ( Site 0708)	Pecs	Baranya
Hungary	Vita Verum Medical Egeszsegugyi Szolgaltato Bt ( Site 0706)	Székesfehérvár	Fejer
Israel	Soroka University Medical Center ( Site 0802)	Beer Sheva
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
Italy	U.O. di Diabetologia dell'Eta Evolutiva - AUSL 2 ( Site 0904)	Caltanissetta
Italy	A.O.Universitaria Meyer ( Site 0901)	Firenze	Toscana
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
Malaysia	Hospital Pulau Pinang. ( Site 1101)	Georgetown	Pulau Pinang
Malaysia	University Malaya Medical Centre ( Site 1100)	Kuala Lumpur
Malaysia	Hospital Universiti Sains Malaysia ( Site 1102)	Kubang Kerian	Kelantan
Malaysia	Hospital Putrajaya ( Site 1103)	Putrajaya	Wilayah Persekutuan Putrajaya
Malaysia	Hospital Taiping ( Site 1104)	Taiping	Perak
Mauritius	Life Nova+ ( Site 1203)	Forbach	Pamplemousses
Mauritius	Wellkin Hospital ( Site 1200)	Moka
Mexico	Centro de Atencion e Investigacion Clinica SC ( Site 1009)	Aguascalientes
Mexico	Centro de Investigacion Medica Aguascalientes ( Site 1000)	Aguascalientes
Mexico	Bio Investigación AMARC, S.C. ( Site 1006)	Ciudad de México	Distrito Federal
Mexico	Consultorio Medico de Endocrinologia Pediatrica ( Site 1002)	Culiacan	Sinaloa
Mexico	Centro de Investigacion Medica de Occidente S.C. ( Site 1001)	Guadalajara	Jalisco
Mexico	Unidad de Investigacion Clinica Cardiometabolica de Occidente ( Site 1007)	Guadalajara	Jalisco
Mexico	Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 1003)	Madero	Tamaulipas
Mexico	CAIMED Investigación en Salud S.A de C.V ( Site 1008)	Mexico	Distrito Federal
Mexico	Unidad Biomedica Avanzada Monterrey S. A. ( Site 1005)	Monterrey	Nuevo Leon
Mexico	Unidad de Medicina Especializada SMA ( Site 1004)	San Juan del Río	Queretaro
Philippines	Davao Doctors Hospital ( Site 1400)	Davao City	Davao Del Sur
Philippines	West Visayas State University Medical Center ( Site 1401)	Iloilo
Philippines	Institute for Studies on Diabetes Foundation Inc. ( Site 1402)	Marikina	National Capital Region
Poland	IN VIVO ( Site 1501)	Bydgoszcz	Kujawsko-pomorskie
Poland	Clinical Medical Research Sp. z o.o. ( Site 1511)	Katowice	Slaskie
Poland	Instytut Diabetologii Sp z o o ( Site 1512)	Warszawa	Mazowieckie
Poland	Poradnia Chorob Metabolicznych. Centrum Zdrowia Tuchow ( Site 1500)	Wierzchoslawice	Malopolskie
Russian Federation	Kazan State Medical University ( Site 1601)	Kazan	Tatarstan, Respublika
Russian Federation	Federal State Budget Institution Endocrinological Research Center ( Site 1611)	Moscow	Moskva
Russian Federation	Children's City Clinical Hospital #1 ( Site 1604)	Novosibirsk	Novosibirskaya Oblast
Russian Federation	Rostov Scientific Research Institution of Obstetrics and Pediatry ( Site 1606)	Rostov-on-Don	Rostovskaya Oblast
Russian Federation	St.Petersburg State Pediatric Medical University ( Site 1600)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Samara City Pediatric Clinical Hospital n.a. N.N. Ivanova ( Site 1610)	Samara	Samarskaya Oblast
Russian Federation	Siberian State Medical University ( Site 1602)	Tomsk	Tomskaya Oblast
Russian Federation	Bashkir State Medical University Hospital ( Site 1603)	Ufa	Baskortostan, Respublika
Russian Federation	Voronezh State Medical University named after N.N.Burdenko ( Site 1608)	Voronezh	Voronezskaja Oblast
Saudi Arabia	King Abdulaziz Medical City - Al Ahsa ( Site 1730)	Al Ahsa	Ar Riyad
Saudi Arabia	King Abdul Aziz Medical City. National Guard Health Affairs ( Site 1715)	Jeddah	Makkah Al Mukarramah
Saudi Arabia	Hera General Hospital ( Site 1725)	Mecca	Al BaHah
Saudi Arabia	King Abdul Aziz Medical City - AlRiyadh ( Site 1700)	Riyadh	Ar Riyad
Saudi Arabia	King Abdul Aziz Medical City - AlRiyadh ( Site 1705)	Riyadh	Ar Riyad
Saudi Arabia	King Salman bin Abdulaziz hospital - Al Riyadh ( Site 1720)	Riyadh	Ar Riyad
Saudi Arabia	King Salman bin Abdulaziz hospital Al Riyadh ( Site 1710)	Riyadh	Ar Riyad
Turkey	Cukurova Uni. Tip Fakultesi ( Site 2403)	Adana
Turkey	Ankara Bilkent Sehir Hastanesi-Çocuk Hastanesi, Çocuk Endokrinoloji ( Site 2407)	Ankara
Turkey	I. U. Cerrahpasa Tip Fakultesi ( Site 2406)	Istambul	Istanbul
Turkey	Marmara Üniversitesi Prof. Dr. Asaf Ataseven Hospital ( Site 2400)	Istanbul
Ukraine	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	Dnipropetrovska Oblast
Ukraine	Institute of Children and Adolescents Health Care of the Academy of Medical Sciences ( Site 1915)	Kharkiv	Kharkivska Oblast
Ukraine	MHI Regional Childrens Clinical Hospital ( Site 1908)	Kharkiv	Kharkivska Oblast
Ukraine	Institute of Endocrinology and Metabolism n.a. Komissarenko ( Site 1905)	Kyiv	Kyivska Oblast
Ukraine	Medical Center Verum ( Site 1913)	Kyiv	Kyivska Oblast
Ukraine	Ukr Center of Endocrine Surgery and Transplatation MOH Ukraine ( Site 1903)	Kyiv	Kyivska Oblast
Ukraine	Odessa Regional Children Clinical Hospital ( Site 1912)	Odesa	Odeska Oblast
Ukraine	Vinnitsa Regional Endocrinology Dispensary, VNMU n.a. M.I.Pyrogov ( Site 1901)	Vinnytsia	Vinnytska Oblast
United Arab Emirates	Rashid Center For Diabetes and Research ( Site 2006)	Ajman
United Arab Emirates	Thumbay University Hospital ( Site 2001)	Ajman
United Arab Emirates	Al Jalila Children s Specialty Hospital ( Site 2004)	Dubai	Dubayy
United Arab Emirates	Dubai Diabetes Center ( Site 2002)	Dubai	Dubayy
United Arab Emirates	Mediclinic City Hospital ( Site 2005)	Dubai	Dubayy
United Arab Emirates	Mustafa Al Qaysi Medical Centre ( Site 2010)	Dubai	Dubayy
United Kingdom	Chelsea and Westminster Hospital ( Site 2103)	London	London, City Of
United Kingdom	Royal London Hospital (Whitechapel) ( Site 2100)	London	London, City Of
United Kingdom	West Middlesex University Hospital ( Site 2104)	London	London, City Of
United States	Barry J. Reiner MD LLC ( Site 2204)	Baltimore	Maryland
United States	The University of Alabama at Birmingham ( Site 2207)	Birmingham	Alabama
United States	CHEAR Center LLC ( Site 2200)	Bronx	New York
United States	ICCT Research International, Inc. ( Site 2211)	Chicago	Illinois
United States	Memorial Regional Hospital-Joe DiMaggio Children's Hospital Division of Pediatric Endocrinology ( Si	Hollywood	Florida
United States	Children's Hospital - Los Angeles ( Site 2201)	Los Angeles	California
United States	Southern Endocrinology and Associates PA ( Site 2218)	Mesquite	Texas
United States	The Children's Hospital of Philadelphia ( Site 2205)	Philadelphia	Pennsylvania
United States	William Beaumont Hospital ( Site 2219)	Royal Oak	Michigan
United States	Center of Excellence in Diabetes and Endocrinology ( Site 2203)	Sacramento	California
United States	Coastal Children''s Services ( Site 2202)	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Colombia,  Costa Rica,  Dominican Republic,  France,  Guatemala,  Hungary,  Israel,  Italy,  Malaysia,  Mauritius,  Mexico,  Philippines,  Poland,  Russian Federation,  Saudi Arabia,  Turkey,  Ukraine,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Hemoglobin A1C (HbA1C) at 24 weeks (pooled ertugliflozin 5 mg and 15 mg versus placebo)	Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples are collected at baseline and Week 24 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 24 minus HbA1C at baseline).	Baseline and 24 weeks
Primary	Number of Participants Who Experience an Adverse Event (AE) over 24 weeks	An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.	Up to 24 weeks
Primary	Number of Participants Who Experience an AE over 54 weeks	An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.	Up to 54 weeks
Primary	Number of Participants Who Discontinue Study Treatment Due to an AE over 24 weeks	An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.	Up to 24 weeks
Primary	Number of Participants Who Discontinue Study Treatment Due to an AE over 54 weeks	An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.	Up to 54 weeks
Secondary	Change from Baseline in Hemoglobin A1C at Week 24 (dose-optimized ertugliflozin versus placebo)	Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples are collected at baseline and Week 24 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 24 minus HbA1C at baseline).	Baseline and 24 weeks
Secondary	Change from Baseline in Hemoglobin A1C at Week 24 (ertugliflozin 5 mg versus placebo)	Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples are collected at baseline and Week 24 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 24 minus HbA1C at baseline).	Baseline and 24 weeks
Secondary	Change from Baseline in Fasting Plasma Glucose (FPG) at 24 Weeks	Blood glucose is measured on a fasting basis. FPG is expressed as mg/dL. Blood is drawn at predose on Day 1 and after 24 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 24 minus FPG at baseline).	Baseline and 24 weeks
Secondary	Change from Baseline in Hemoglobin A1C at 54 Weeks	Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples are collected at baseline and Week 54 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 54 minus HbA1C at baseline).	Baseline and 54 weeks
Secondary	Change from Baseline in FPG at 54 Weeks	Blood glucose is measured on a fasting basis. FPG is expressed as mg/dL. Blood is drawn at predose on Day 1 and after 54 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 54 minus FPG at baseline).	Baseline and 54 weeks

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary