A Phase IIa, Multicenter, Randomized, Placebo- and Active-Comparator Controlled, Cross-Over Clinical Trial to Study the Safety and Efficacy of MK-3577 in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 118
- 主要终点
- Number of Participants With At Least One Adverse Event (AE) in the Treatment or Post-Treatment Periods
研究概览
简要总结
This study assessed the safety and efficacy of MK-3577. The primary efficacy hypothesis was that, after 4 weeks of treatment, either the morning (AM) administration or the evening (PM) administration of MK-3577 provides superior reduction of 24-hour weighted mean glucose (WMG) levels compared to placebo (PLA). The primary safety hypothesis was that MK-3577 is well tolerated compared to placebo.
详细描述
This was a 4-period/5-treatment crossover study. Each period was 4 weeks. The 5 treatments consisted of MK-3577 10 mg once daily (QD) in the AM, MK-3577 6 mg QD in the evening (PM), MK-3577 25 mg twice daily (BID), metformin 1000 mg BID, and placebo to MK-3577/placebo to metformin. Participants were to be randomized to one of 14 treatment sequence arms. A subset of participants in each group was to domicile (stay overnight) at selected clinical sites at Baseline, Week 4 (end of Period 1), and Week 8 (end of Period 2) to undergo 24-hr blood sample.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has type 2 diabetes
- •Participant is either not taking antihyperglycemic medications for the last 10 weeks OR is taking a single oral antihyperglycemic medication (but not a Peroxisome Proliferator-Activated Receptor gamma [PPARg] agonist) OR is taking a low-dose combination oral antihyperglycemic medication (not a PPARg agonist) at dose less than or equal to 50% of the maximum dose
- •Female participant is unable to have children
排除标准
- •Participant has a history of type 1 diabetes or ketoacidosis
- •Participant has been treated with a PPARg agonist in the last 12 weeks
- •Participant has been treated with insulin in the last 12 weeks
- •Participant has had prescription lipid-modifying drug therapy in the last 12 weeks
- •Participant has a history of coronary artery disease
- •Participant has had a stroke or transient ischemic attack
- •Participant has congestive heart failure
研究组 & 干预措施
MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: MK-3577 (Drug)
PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to MK-3577 (Drug)
PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to Metformin (Drug)
MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: MK-3577 (Drug)
MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to Metformin (Drug)
MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed MK- 3577 25 mg BID for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed MK- 3577 25 mg BID for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4)
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8)
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: MK-3577 (Drug)
PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to MK-3577 (Drug)
PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9)
Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to Metformin (Drug)
MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10)
Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)
Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: MK-3577 (Drug)
MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to MK-3577 (Drug)
MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11)
Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2.
干预措施: Placebo to Metformin (Drug)
MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.
干预措施: MK-3577 (Drug)
MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12)
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4.
干预措施: Placebo to MK-3577 (Drug)
PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)
Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2.
干预措施: MK-3577 (Drug)
PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)
Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2.
干预措施: Metformin (Drug)
PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13)
Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2.
干预措施: Placebo to Metformin (Drug)
METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)
Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2.
干预措施: MK-3577 (Drug)
METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)
Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2.
干预措施: Placebo to MK-3577 (Drug)
METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)
Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2.
干预措施: Metformin (Drug)
METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14)
Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2.
干预措施: Placebo to Metformin (Drug)
结局指标
主要结局
Number of Participants With At Least One Adverse Event (AE) in the Treatment or Post-Treatment Periods
时间窗: From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks).
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Change From Baseline (BL) After 4-Week Treatment in Weighted Mean Glucose (WMG)
时间窗: Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit
The primary efficacy outcome in this study was the assessment of 24-hour weighted mean glucose (WMG) levels for domiciled participants after 4-week treatment (Periods 1 and 2 only). At selected study sites, a subset of participants domiciled (stayed) overnight and underwent 24-hour blood sampling at the Week 0 Visit (Baseline), Week 4 Visit (end of Period 1), and Week 8 Visit (end of Period 2). Domiciled participants were not expected to follow a weight-maintaining diet while receiving standard meals from a dietician or licensed healthcare professional. WMG was calculated as the weighted average value of the glucose from the 24-hour blood sample (for Baseline, Week 4, and Week 8) and analyzed using a Longitudinal Data Analysis (LDA) model. Results were expressed as the change from baseline after 4-week treatment in 24-hour WMG.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: From first dose of study treatment (Week 0 Visit) to Week 16 Visit (up to 16 weeks).
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
次要结局
- Change From BL After 4-Week Treatment in 2-hour Post-Meal Glucose (PMG) Levels(Week 0 Visit (Baseline), Week 4 Visit, Week 8 visit)
- Change From Baseline (BL) After 4-Week Treatment in Fasting Plasma Glucose (FPG)(Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit)
- Percentage Change From Baseline (BL) After 4-Week Treatment in Low-Density Lipoprotein C (LDL-C) Levels(Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit)