Study of MK-8242 Alone and in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia (P07649)
2018年7月26日 更新者：Merck Sharp & Dohme LLC
A Phase I Study to Evaluate the Safety and Tolerability and Pharmacokinetic/Pharmacodynamics of MK-8242 Administered Alone and in Combination With Chemotherapy in Subjects With Refractory or Recurrent Acute Myelogenous Leukemia (Protocol No. P07649 (005))
This is a study of MK-8242 alone and in combination with cytarabine in adult participants with refractory or recurrent acute myelogenous leukemia (AML).
The study will have 2 Arms.
Arm A is for participants with refractory or recurrent AML who are considered ineligible for standard chemotherapy.
In Part 1 of Arm A, participants will receive MK-8242 monotherapy in escalating doses to determine the recommended phase 2 dose [RP2D].
In Part 2, participants will receive monotherapy with MK-8242 to confirm the RP2D and assess preliminary efficacy.
Arm B is for participants with recurrent AML following an initial complete remission (CR) or CR with incomplete marrow recovery (CRi) of 6 to 12 months duration.
In Part 1 of Arm B, participants will receive MK-8242 in escalating doses + cytarabine to determine the RP2D in combination with cytarabine.
In Part 2, participants will receive MK-8242 + cytarabine to confirm the RP2D and assess preliminary efficacy.
The pharmacokinetics of MK-8242 will be studied in both arms.
With Amendment 4 (22 August 2013) a 21-day dosing cycle is added, with MK-8242 being given on Days 1-7 of each 21-day cycle in both the monotherapy and combination therapy arms; data from Arm A will be used to determine whether a participant receives 21-day or 28-day therapy in Arm B.
研究概览
研究类型
介入性
注册 (实际的)
26
阶段
- 阶段1
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion criteria:
- For Arm A Part 1 (monotherapy/dose escalation): refractory or recurrent AML, not an appropriate candidate for standard therapy
- For Arm A Part 2 (monotherapy/dose confirmation/cohort expansion): refractory or recurrent AML, not an appropriate candidate for standard therapy, and have wild type p53 gene mutation analysis
- For Arm B Part 1 (combination therapy/dose escalation): recurrent AML having achieved an initial CR or CRi of 6-12 months duration and age ≥18 years old and <70 years old
- For Arm B Part 2 (combination therapy/dose confirmation/cohort expansion): recurrent AML having achieved an initial CR or CRi of 6-12 months duration, age ≥18 years old and <70 years old, and have wild type P53 gene mutation analysis
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 for all Arm A, or 0 or 1 for all Arm B
- Negative pregnancy test within 72 hours of the first dose of study medication
- Female participants and male participants and their partners who are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of study therapy
- Adequate organ function
- Recovered from the effects of any prior surgery, radiotherapy or anti-neoplastic treatment, with the exception of alopecia
- Must be able to swallow, retain, and absorb oral medications and oral nutrition
- Must follow the appropriate washout period for prohibited treatments
Exclusion criteria:
- Active malignancy other than AML
- Leptomeningeal leukemia requiring intrathecal therapy
- For Arm A and B, Part 1 only: history of myelodysplastic syndrome (MDS)
- For Arm A and B, Part 2: AML in the background of MDS may be included
- Isolated extramedullary leukemia without also meeting bone marrow criteria for acute leukemia
- AML blast crisis of chronic myelogenous leukemia (CML)
- Bone marrow transplant with active graft-versus host disease (GVHD) or who receives immunosuppressive therapy
- Uncontrolled active infection that requires systemic treatment
- Clinically significant hepatitis at Screening, or hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive
- Persistent, unresolved, drug-related toxicity
- Breast-feeding, pregnant, intends to become pregnant or intends to breast feed during the study or has a positive pregnancy test at Screening
- A person participating in any other clinical study with a potentially therapeutic agent or who has received another investigational product within 5 half-lives (if the half-life is known) or 28 days (if the half-life is unknown) prior to Day 1 of cycle 1
- A participant who, within the past 6 months, has had any of the following: myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or uncontrolled seizure disorder (i.e., seizures within the past 6 months)
- A participant who, at the time of Screening, presents with: unstable or uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality
- Known bleeding disorder, e.g. hemophilia or disseminated intravascular coagulopathy or on anti-coagulation therapy
- For Arm B only: Known hypersensitivity to cytarabine
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Pt 1 Arm A: MK-8242 30 mg QD
Participants received MK-8242 30 mg once daily (QD) monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
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实验性的：Pt 1 Arm A: MK-8242 60 mg QD
Participants received MK-8242 60 mg QD monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
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实验性的：Pt 1 Arm A: MK-8242 120 mg QD
Participants received MK-8242 120 mg QD monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
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实验性的：Pt 1 Arm A: MK-8242 250 mg QD
Participants received MK-8242 250 mg QD monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
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实验性的：Pt 1 Arm A: MK-8242 120 mg BID
Participants received MK-8242 120 mg twice daily (BID) monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles (except Cycle 1 Day 7 on which MK-8242 120 mg was administered QD in the morning) in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
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实验性的：Pt 1 Arm A: MK-8242 170 mg BID
Participants received MK-8242 170 mg BID monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles (except Cycle 1 Day 7 on which MK-8242 170 mg was administered QD in the morning) in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
|
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实验性的：Pt 1 Arm A: MK-8242 210 mg BID
Participants received MK-8242 210 mg BID monotherapy on Days 1-7 of a 21-day cycle up to a maximum of 12 cycles (except Cycle 1 Day 7 on which MK-8242 210 mg was administered QD in the morning) in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
|
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实验性的：Pt 1 Arm A: MK-8242 250 mg BID
Participants received MK-8242 250 mg BID monotherapy on Days 1-7 and Days 15-21 of a 28-day cycle up to a maximum of 12 cycles (except Cycle 1 Day 7 on which MK-8242 250 mg was administered QD in the morning) in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
|
|
实验性的：Pt 1 Arm A: MK-8242 300 mg BID
Participants received MK-8242 300 mg BID monotherapy on Days 1-7 of a 21-day cycle up to a maximum of 12 cycles (except Cycle 1 Day 7 on which MK-8242 300 mg was administered QD in the morning) in Part 1 Arm A.
|
MK-8242 capsules, orally, once per day on Days 1-7 and Days 15-21 of each 28-day cycle (except Cycle 1 Day 7) up to a maximum of 12 cycles.
Starting dose will be 30 mg and will be escalated in successive cohorts until maximum tolerated dose (MTD) is established.
Beginning at a dose level of ≥120 mg total daily dose (TDD), the dosing regimen will switch to twice daily (BID).
Amendment 4 added a 21-day dosing cycle in which MK-8242 would be given BID on Days 1-7 of each cycle, at the assigned dose level.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Number of Participants With Dose Limiting Toxicities (DLTs)
大体时间：Up to 28 days (Cycle 1) for non-hematologic toxicities and 42 days (Cycle 1) for hematologic toxicities
|
DLTs were identified using Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 for toxicities attributable to the study drug.
Hematologic DLTs were defined in the absence of morphological evidence of acute leukemia in the marrow if 1) bone marrow: aplastic marrow with <5% cellularity without erythroid, myeloid, or megakaryocytic precursors and 2) peripheral blood: absolute neutrophil count (ANC) <100/µL, platelet count <10,000/µL, and transfusion-dependent anemia.
Non-hematologic DLTs were defined as any ≥Grade 3 toxicity with the following exceptions/clarifications: 1) infection, fatigue, anorexia, or alopecia are not included in determination of the DLT 2) Grade 3 nausea, vomiting, diarrhea, or dehydration occurring in a setting of inadequate treatment 3) any abnormal non-hematological laboratory value ≥Grade 3 will be considered a DLT after 72 hours of appropriate medical intervention if not related to an underlying disease or not attributable to another event.
|
Up to 28 days (Cycle 1) for non-hematologic toxicities and 42 days (Cycle 1) for hematologic toxicities
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Number of Participants With Complete Remission (CR) at RP2D
大体时间：End of Treatment (up to 198 days)
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Clinical activity of MK-8242 given as monotherapy in participants with refractory or recurrent AML measured as participants who achieved CR according to Cheson (2003) criteria at the RP2D.
The outcome analysis was not performed since the RP2D for MK-8242 monotherapy could not be established due to early termination of the study.
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End of Treatment (up to 198 days)
|
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Number of Participants With Complete Remission With Incomplete Marrow Recovery (CRi) at RP2D
大体时间：End of Treatment (up to 198 days)
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Clinical activity of MK-8242 given as monotherapy in participants with refractory or recurrent AML measured as participants who achieved CRi according to Cheson (2003) criteria at the RP2D.
The outcome analysis was not performed since the RP2D for MK-8242 monotherapy could not be established due to early termination of the study.
|
End of Treatment (up to 198 days)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of Participants With CR at Dose Levels Other Than RP2D
大体时间：End of Treatment (up to 198 days)
|
Clinical activity of MK-8242 given as monotherapy in participants with refractory or recurrent AML measured as participants who achieved CR according to Cheson (2003) criteria at dose levels other than RP2D.
CR is defined as a morphologic leukemia-free state with a neutrophil count ≥1,000/µL, a platelet count ≥100,000/µL, no extramedullary disease, and RBC transfusion independence.
Presented outcome values are not stratified for dose levels other than RP2D; the RP2D for MK-8242 monotherapy could not be established due to early termination of the study.
|
End of Treatment (up to 198 days)
|
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Number of Participants With CRi at Dose Levels Other Than RP2D
大体时间：End of Treatment (up to 198 days)
|
Clinical activity of MK-8242 given as monotherapy in participants with refractory or recurrent AML measured as participants who achieved CRi according to Cheson (2003) criteria at dose levels other than RP2D.
CRi is defined as fulfillment of all CR criteria with exceptions for residual neutropenia (<1,000/µL), thrombocytopenia (<100,000/µL), and RBC transfusion dependence.
Presented outcome values are not stratified for dose levels other than RP2D; the RP2D for MK-8242 monotherapy could not be established due to early termination of the study.
|
End of Treatment (up to 198 days)
|
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Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24hr) for MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, and 24 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], and 24 [Day 7 only] hrs postdose)
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AUC(0-24hr) defined as AUC from time zero to 24 hours was determined for Cycle 1 Days 1 and 7 of MK-8242 QD and BID dosing using the trapezoidal up/log trapezoidal down method.
For the BID arms, a projection beyond the last sampled time was made if a linear terminal elimination phase half-life was identified with three time-points after Tmax.
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, and 24 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], and 24 [Day 7 only] hrs postdose)
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Area Under the Concentration-time Curve From Time 0 to Last (AUC0-last) for MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 [Day 7 only] hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
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AUC(0-last) defined as AUC from time zero to the time of last quantifiable sample was determined for Cycle 1 Days 1 and 7 of MK-8242 QD and BID dosing using the trapezoidal up/log trapezoidal down method.
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 [Day 7 only] hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
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Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) for MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1 Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24, 48 hrs postdose)
|
AUC0-∞ defined as AUC from time zero to infinity was determined for Cycle 1 Day 7 of MK-8242 QD and BID dosing using the trapezoidal up/log trapezoidal down method.
Projection beyond the last sampled time was made if a linear terminal elimination phase half-life was identified with three time-points after Tmax (condition not met for 60 QD and 120 BID dose groups).
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1 Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24, 48 hrs postdose)
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Maximum Plasma Concentration (Cmax) of MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 [Day 7 only] hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
|
Cmax was determined for Cycle 1 Days 1 and 7 of MK-8226 QD and BID dosing.
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 [Day 7 only] hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
|
|
Time to Maximum Concentration (Tmax) of MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 [Day 7 only] hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
|
Tmax was determined for Cycle 1 Days 1 and 7 of MK-8226 QD and BID dosing.
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1, Day 1 and Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 [Day 7 only] hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
|
|
Apparent Terminal Half-life (t1/2) for MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1 Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24, 48 hrs postdose)
|
Elimination phase t1/2 was determined for Cycle 1 Day 7 of MK-8242 QD and BID dosing.
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1 Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24, 48 hrs postdose)
|
|
Accumulation Ratio (R) of MK-8242 Alone and in Combination With Cytarabine
大体时间：Cycle 1 Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
|
The accumulation ratio (R) at steady state (based on dosing interval and apparent terminal half-life (t1/2)) for MK-8242 alone was not determined due to confounding of results by significant concentrations of a drug metabolite (M16).
Analysis for the combination therapy was not performed due to early termination of the study (Study Arm B was not performed).
|
Cycle 1 Day 7 (QD arms: predose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 24, and 48 hrs postdose; BID arms: predose and 0.5, 1, 2, 4, 6, 8, 12 [optional], 24 [Day 7 only], 48 [Day 7 only] hrs postdose)
|
|
Urine Concentration of MK-8242 (Part 2 Arm A Only)
大体时间：Day 1 (predose and postdose) and Day 7 (postdose)
|
The urine concentration of MK-8242 assessed as a measure of drug bioavailability was not determined due to early termination of the study (Study Part 2 was not performed).
|
Day 1 (predose and postdose) and Day 7 (postdose)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2011年11月18日
初级完成 (实际的)
2014年9月5日
研究完成 (实际的)
2014年9月5日
研究注册日期
首次提交
2011年10月11日
首先提交符合 QC 标准的
2011年10月11日
首次发布 (估计)
2011年10月13日
研究记录更新
最后更新发布 (实际的)
2018年8月27日
上次提交的符合 QC 标准的更新
2018年7月26日
最后验证
2018年7月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.