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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 104
- 主要终点
- Change From Baseline in Hemoglobin A1C (HbA1C) at Week 24 (Combined Ertugliflozin Versus Placebo)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •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.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •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.
研究组 & 干预措施
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.
干预措施: Ertugliflozin 5 mg (Drug)
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.
干预措施: Placebo to ertugliflozin 15 mg (Drug)
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.
干预措施: Insulin (Biological)
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.
干预措施: Metformin (Drug)
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.
干预措施: Ertugliflozin 5 mg (Drug)
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.
干预措施: Placebo to ertugliflozin 15 mg (Drug)
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.
干预措施: Insulin (Biological)
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.
干预措施: Metformin (Drug)
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.
干预措施: Ertugliflozin 5 mg (Drug)
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.
干预措施: Ertugliflozin 15 mg (Drug)
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.
干预措施: Placebo to ertugliflozin 15 mg (Drug)
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.
干预措施: Placebo to ertugliflozin 5 mg (Drug)
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.
干预措施: Insulin (Biological)
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.
干预措施: Metformin (Drug)
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.
干预措施: Placebo to ertugliflozin 15 mg (Drug)
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.
干预措施: Placebo to ertugliflozin 5 mg (Drug)
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.
干预措施: Insulin (Biological)
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.
干预措施: Metformin (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin A1C (HbA1C) at Week 24 (Combined Ertugliflozin Versus Placebo)
时间窗: Baseline and Week 24
Hemoglobin A1C is a measure of the percentage of glycated HbA1C in the blood. Participant whole blood samples were collected at baseline and Week 24 to determine the A1C change from baseline (i.e., % A1C at Week 24 minus % A1C at baseline). A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. The Bayesian mean change from baseline for each combined ertugliflozin and placebo are reported. Per protocol, the ertugliflozin arms are combined for this analysis.
Number of Participants Who Experienced an Adverse Event (AE) Up to Week 24
时间窗: Up to Week 24
An adverse event -- Select --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. Per protocol, the ertugliflozin arms are combined for this analysis.
Number of Participants Who Experienced an AE Up to Week 54
时间窗: Up to Week 54
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. Per protocol, the ertugliflozin arms are combined for this analysis.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 24
时间窗: Up to Week 24
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. Per protocol, the ertugliflozin arms are combined for this analysis.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to Week 54
时间窗: Up to Week 54
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. Per protocol, the ertugliflozin arms are combined for this analysis.
次要结局
- Change From Baseline in Hemoglobin A1C at Week 24 (Dose-optimized Ertugliflozin Versus Placebo)(Baseline and Week 24)
- Change From Baseline in Hemoglobin A1C at Week 24 (5 mg Ertugliflozin Versus Placebo)(Baseline and Week 24)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24(Baseline and Week 24)
- Change From Baseline in Hemoglobin A1C at Week 54(Baseline and Week 54)
- Change From Baseline in FPG at Week 54(Baseline and Week 54)