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Trial record 1 of 1 for:    8835-059
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Ertugliflozin Type 2 Diabetes Mellitus (T2DM) Pediatric Study (MK-8835/PF-04971729) (MK-8835-059)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04029480
Recruitment Status : Recruiting
First Posted : July 23, 2019
Last Update Posted : May 9, 2023
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Ertugliflozin 5 mg Drug: Ertugliflozin 15 mg Drug: Placebo to ertugliflozin 15 mg Drug: Placebo to ertugliflozin 5 mg Biological: Insulin Drug: Metformin Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 8, 2019
Estimated Primary Completion Date : July 10, 2025
Estimated Study Completion Date : July 10, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Ertugliflozin 5 mg/5 mg

All participants will initially receive ertugliflozin (ERTU) 5 mg once daily (QD) and placebo to ERTU 15 mg QD for 12 weeks. At the second randomization at Week 12 (WK12), all participants that do not meet the up-titration criteria will remain on ERTU 5 mg and placebo to ERTU 15 mg from WK12 to WK54. Approximately half the participants who meet the up-titration criteria at the second randomization at WK12 will also remain on ERTU 5 mg and placebo to ERTU 15 mg from WK12 to WK54.

Note: For participants not on insulin, the up-titration criterion at the second randomization at WK12 is HbA1C ≥7.0% (53 mmol/mol) and for participants on insulin, a fasting fingerstick glucose (FFSG) of ≥110 mg/dL (6.1 mmol/L) will be required in addition to HbA1C ≥7.0% (53 mmol/mol). Participants will remain on their background metformin with/without insulin treatment throughout the study.

 Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg, oral, 1 tablet QD
Other Name: MK-8835

Drug: Placebo to ertugliflozin 15 mg
Placebo to ertugliflozin 15 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.
Experimental: Ertugliflozin 5 mg/15 mg

All participants will initially receive ERTU 5 mg QD and placebo to ERTU 15 mg QD for 12 weeks. At the second randomization at WK12, approximately half the participants who meet the up-titration criteria at the second randomization will up-titrate to ERTU 15 mg and placebo to ERTU 5 mg from WK12 to WK54.

Note: For participants not on insulin, the up-titration criterion at the second randomization at WK12 is HbA1C ≥7.0% (53 mmol/mol) and for participants on insulin, a FFSG of ≥110 mg/dL (6.1 mmol/L) will be required in addition to HbA1C ≥7.0% (53 mmol/mol). Participants will remain on their background metformin with/without insulin treatment throughout the study.

 Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg, oral, 1 tablet QD
Other Name: MK-8835

Drug: Ertugliflozin 15 mg
Ertugliflozin 15 mg, oral, 1 tablet QD
Other Name: MK-8835

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

Drug: 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.
Placebo Comparator: Placebo
At the first randomization, participants receive placebo to ERTU 5 mg and placebo to ERTU 15 mg QD for 12 weeks. Participants in the placebo group with HbA1C ≥7.0% (53 mmol/mol) at WK12 will be mock titrated. Note: The up-titration criteria for participants on insulin will include a FFSG of ≥110 mg/dL (6.1 mmol/L) in addition to HbA1C ≥7.0% (53 mmol/mol) at WK12. Participants will continue to receive placebo to ERTU 5 mg and placebo to ERTU 15 mg QD from WK24 to WK54. Participants will remain on their background metformin with/without insulin treatment throughout the study.
 Drug: Placebo to ertugliflozin 15 mg
Placebo to ertugliflozin 15 mg, oral, 1 tablet QD

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


Outcome Measures
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Primary Outcome Measures :
  1. Change from Baseline in Hemoglobin A1C (HbA1C) at 24 weeks (pooled ertugliflozin 5 mg and 15 mg versus placebo) [ Time Frame: Baseline and 24 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 24 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 24 minus HbA1C at baseline).

  2. Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to 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.

  3. Number of Participants Who Experience an AE [ Time Frame: Up to 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.

  4. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to 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.

  5. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to 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.


Secondary Outcome Measures :
  1. Change from Baseline in Hemoglobin A1C at Week 24 (dose-optimized ertugliflozin versus placebo) [ Time Frame: Baseline and 24 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 24 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 24 minus HbA1C at baseline).

  2. Change from Baseline in Hemoglobin A1C at Week 24 (ertugliflozin 5 mg versus placebo) [ Time Frame: Baseline and 24 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 24 to determine the least squares mean HbA1C change from baseline (i.e., HbA1C at Week 24 minus HbA1C at baseline).

  3. Change from Baseline in Fasting Plasma Glucose (FPG) at 24 Weeks [ Time Frame: Baseline and 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).

  4. Change from Baseline in Hemoglobin A1C at 54 Weeks [ Time Frame: Baseline and 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).

  5. Change from Baseline in FPG at 54 Weeks [ Time Frame: Baseline and 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).


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04029480


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Pfizer
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04029480    
Other Study ID Numbers: 8835-059
MK-8859-059 ( Other Identifier: Merck Protocol Number )
PHRR190913-002184 ( Registry Identifier: PHRR )
2022-501085-21-00 ( Registry Identifier: EU CT )
First Posted: July 23, 2019    Key Record Dates
Last Update Posted: May 9, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
 Ertugliflozin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action