Single Center, Randomized, Placebo-Controlled Trial to Establish Maximum Tolerated Dose, Optimal Titration Schedule, Safety, Tolerability, and Pharmacokinetics of Org 26576 in Patients Diagnosed With Major Depressive Disorder (Protocol No. P174001)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 主要终点
- Part 1: Number of Participants With Serious Adverse Events (SAEs)
研究概览
简要总结
Trial to determine the maximum tolerated dose (MTD) based on safety and tolerability of MK-8777 (Org 26576, SCH 900777) in participants with major depressive disorder.
详细描述
This is a randomized, placebo-controlled, safety and tolerability study examining MK-8777 in participants with major depressive disorder. In Part I of the trial, four different cohorts of six participants each will receive multiple rising doses of MK-8777 (ranging from 100 mg twice a day [BID] to 300 mg BID) or placebo for up to 16 days. In Part 2, a new cohort of participants will be randomly assigned to receive 100 mg BID of MK-8777, 400 mg BID of MK-8777, or placebo. Following titration (3 days per step), participants will be maintained on the assigned BID dose until Day 27, followed by one day of once a day (QD) dosing, for a total of 28 days. There were 11 treatment arms in total for Part 1 and Part 2 (see Interventions).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female who is non-pregnant, nonlactating, using an acceptable method of birth control, or is not of child-bearing potential;
- •be diagnosed with current major depressive disorder either mild or severe, as evidenced by a score of at least 9 but not more than 20 on the Quick Inventory of Depression Symptomatology - Clinician Rated (QIDS-C);
- •be anti-depressant naïve;
- •be able to refrain from all use of grapefruit containing products from the time of admission until the last assessment is performed at discharge;
- •smokes less than or equal to 10 cigarettes or equivalent daily.
排除标准
- •has any current and primary Axis I disorder other than major depressive disorder;
- •has any history of bipolar I or II disorder, dysthymia, psychotic depression, psychotic disorders, posttraumatic stress disorder, borderline personality disorder, obsessive compulsive disorder, or eating disorder;
- •the duration of the current depressive episode is longer than 2 years at screening;
- •has any history of a significant suicide attempt, or poses a current risk of attempting suicide;
- •is known to be human immunodeficiency virus (HIV) positive, or positive for hepatitis B surface antigen or hepatitis A antibodies or hepatitis C total antibodies;
- •has any clinically significant concurrent endocrine, renal, respiratory, cardiovascular, hematological, immunological, cerebrovascular, neurological, malignancy, or any other concurrent medical condition, or has any history of diabetes mellitus;
- •donation of blood within 60 days prior to the anticipated first dose of trial medication.
研究组 & 干预措施
Part 1: Block A MK-8777
Participants receive MK-8777 initiated at 100 mg BID and titrated to a maximum of 600 mg BID. Participants receive MK-8777 for a total of 16 days.
干预措施: MK-8777 (Drug)
Part 1: Block A Placebo
Participants receive placebo BID for a total of 16 days.
干预措施: Placebo (Drug)
Part 1: Block B MK-8777
Participants receive MK-8777 initiated at 200 mg BID and titrated to a maximum of 600 mg BID. Participants receive MK-8777 for a total of 13 days.
干预措施: MK-8777 (Drug)
Part 1: Block B Placebo
Participants receive placebo BID for a total of 13 days.
干预措施: Placebo (Drug)
Part 1: Block C MK-8777
Participants receive MK-8777 initiated at 300 mg BID and titrated to a maximum of 600 mg BID. Participants receive MK-8777 for a total of 10 days.
干预措施: MK-8777 (Drug)
Part 1: Block C Placebo
Participants receive placebo BID for a total of 10 days.
干预措施: Placebo (Drug)
Part 1: Block D MK-8777
Participants receive MK-8777 initiated at 100 mg BID and titrated to a maximum dose determined by the results of Block A. Participants receive MK-8777 for a total of 13 days.
干预措施: MK-8777 (Drug)
Part 1: Block D Placebo
Participants receive placebo BID for a total of 13 days.
干预措施: Placebo (Drug)
Part 2: MK-8777 200 mg
Participants receive MK-8777 100 mg BID for 27 days followed by one day of 100 mg QD. Participants receive MK-8777 for a total of 28 days.
干预措施: MK-8777 (Drug)
Part 2: MK-8777 800 mg
Participants receive MK-8777 200 mg BID for 3 days followed by 400 mg BID for 24 days followed by one day of 400 mg QD. Participants receive MK-8777 for a total of 28 days.
干预措施: MK-8777 (Drug)
Part 2: Placebo
Participants receive placebo BID for 27 days followed by one day of placebo QD. Participants receive placebo for 28 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to 30 days following the last dose of study drug (Up to 46 days)
An SAE is defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Part 1: Number of Participants With Moderate Intensity Adverse Events (AEs)
时间窗: Up to 7 days following the last dose of study drug (Up to 23 days)
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 study drug, whether or not considered related to the use of the product. A moderate intensity AE is defined as an AE that causes no significant interference with functioning.
Part 1: Number of Participants With AEs Leading to Discontinuation of Study Drug
时间窗: Up to the last dose of study drug (Up to 16 days)
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 study drug, whether or not considered related to the use of the product. Discontinuation refers to discontinuation of study drug (MK-8777 or Placebo).
Part 2: Number of Participants With AEs
时间窗: Up to 7 days following the last dose of study drug (Up to 35 days)
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 study drug, whether or not considered related to the use of the product.
Part 2: Number of Participants With AEs Leading to Discontinuation of Study Drug
时间窗: Up to the last dose of study drug (Up to 28 days)
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 study drug, whether or not considered related to the use of the product. Discontinuation refers to discontinuation of study drug (MK-8777 or Placebo).
次要结局
- Part 1: Change From Baseline in the Montgomery-Ashberg Depression Rating Scale (MADRS)(Baseline and end of treatment (Up to Day 16))
- Part 2: Change From Baseline in the MADRS(Baseline and end of treatment (Up to Day 28))