A Double Blind, Placebo Controlled, Randomized, Two Period 4-Arm Trial to Investigate the Dose-Related Efficacy and Safety of Org 26576 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 主要终点
- Change From Baseline in Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Score
研究概览
简要总结
This is a Phase 2 multicenter, randomized, double-blind trial of MK-8777 (Org 26576, SCH 900777) in adult subjects with Attention-Deficit/Hyperactivity Disorder (ADHD). MK-8777 or placebo will be administered in a crossover fashion for two 3-week treatment periods. The two 3-week treatment periods will be separated by a 2-week placebo washout period.
The primary objective is to compare the efficacy of various doses of MK-8777 to that of placebo in the treatment of ADHD symptoms in adults.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •are between 18-50 years, inclusive;
- •are male; or female who are non-pregnant, non-lactating and using an acceptable method of birth control (intrauterine device, double-barrier method, hormonal contraceptives); or female of non-childbearing potential if they are a) surgically sterile (tubal ligation, hysterectomy and/or bilateral oophorectomy) and provide documentation of the procedure by operative report or ultrasound scan, or b) post-menopausal for greater than one year with follicle stimulating hormone (FSH) level greater than or equal to 40 mIU/mL at screening. All females must have a negative serum pregnancy test at screening;
- •are outpatients;
- •provide written informed consent
- •are fluent in the language of the investigator,
- •are able to discontinue the use of any psychotropic medications for the treatment of ADHD symptoms at screening;
- •meet strict operational criteria for adult ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TRTM)
- •have a Clinical Global Impression ADHD score of 4 or higher at screening
排除标准
- •have any clinically significant concurrent medical condition (endocrine, renal, respiratory, cardiovascular, hematological, immunological, cerebrovascular, neurological, anorexia, obesity or malignancy) that has become unstable and may interfere with the interpretation of safety and efficacy evaluations.
- •have any clinically significant abnormal laboratory, vital sign, physical examination, or electrocardiogram (ECG) findings at screening that, in the opinion of the investigator, may interfere with the interpretation of safety or efficacy evaluations.
- •have any history of liver disease (e.g., cirrhosis, hepatitis), or liver injury;(history of hepatitis A greater than one year prior to screening is acceptable); any abnormal clinically significant findings at screening on liver laboratory parameters (serum glutamic-pyruvic transaminase [SGPT], serum glutamic oxaloacetic transaminase [SGOT], gamma-glutamyltransferase [GGT], lactate dehydrogenase [LDH], bilirubin, albumin, protein, alkaline phosphatase);
- •have a seizure disorder beyond childhood or are taking any anticonvulsants to prevent seizures;
- •have known serological evidence of human immunodeficiency virus (HIV) antibody;
- •have a positive test result at screening on hepatitis B surface antigen or hepatitis A immunoglobulin M (IgM) antibodies or hepatitis C total antibodies;
- •are pregnant as confirmed by a positive serum pregnancy test at screening;
- •have QTc values >450 msec at screening using Fridericia's QTc formula;
- •have a confirmed positive result in the alcohol/drug screen test for alcohol, illegal or non-prescribed drugs at screening (except marijuana/ tetrahydrocannabinol [THC]);
- •have a confirmed positive result in the alcohol/drug screen re-test for marijuana/THC;
- •have current or lifetime history of bipolar and psychotic disorders;
- •have a current major depression disorder, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder and eating disorder (also if treated but not currently symptomatic);
- •have a current comorbid dysthymia or social anxiety disorder that is currently treated with psychotropic medication;
- •have a current untreated social anxiety disorder that may interfere with the assessment of ADHD in the investigator's opinion;
- •present an imminent risk of self-harm or harm to others;
- •have any history of a significant suicide attempt, or possess a current risk of attempting suicide, in the investigator's opinion, based on clinical interview and responses provided on the Beck Scale for Suicidal Ideation (BSS);
- •have a history of jailing or imprisonment in the past 6 months due to worsening of symptoms of ADHD;
研究组 & 干预措施
MK-8777 FD→PBO
Participants receive a fixed dose (FD) of MK-8777 100 mg twice each day (BID) for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive a fixed dose of placebo (PBO) BID for 3 weeks (Treatment Period 2).
干预措施: MK-8777 (Drug)
MK-8777 FD→PBO
Participants receive a fixed dose (FD) of MK-8777 100 mg twice each day (BID) for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive a fixed dose of placebo (PBO) BID for 3 weeks (Treatment Period 2).
干预措施: Placebo (Drug)
PBO→MK-8777 FD
Participants receive a fixed dose of placebo BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive a fixed dose of MK-8777 100 mg BID for 3 weeks (Treatment Period 2).
干预措施: MK-8777 (Drug)
PBO→MK-8777 FD
Participants receive a fixed dose of placebo BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive a fixed dose of MK-8777 100 mg BID for 3 weeks (Treatment Period 2).
干预措施: Placebo (Drug)
MK-8777 RD→PBO
Participants receive rising doses (RD) of MK-8777 100-300 mg BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive rising doses of placebo BID for 3 weeks (Treatment Period 2).
干预措施: MK-8777 (Drug)
MK-8777 RD→PBO
Participants receive rising doses (RD) of MK-8777 100-300 mg BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive rising doses of placebo BID for 3 weeks (Treatment Period 2).
干预措施: Placebo (Drug)
PBO→MK-8777 RD
Participants receive rising doses of placebo BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive rising doses of MK-8777 100-300 mg BID for 3 weeks (Treatment Period 2).
干预措施: MK-8777 (Drug)
PBO→MK-8777 RD
Participants receive rising doses of placebo BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive rising doses of MK-8777 100-300 mg BID for 3 weeks (Treatment Period 2).
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Score
时间窗: Baseline (BL) and Day 7, Day 14, Day 21
The AISRS is an 18-item clinician-rated instrument for assessing the 18 core symptoms of ADHD corresponding to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnostic symptoms for adults. Based on the clinician's rating for each of the symptoms using a 4-point scale (0=None to 3=Severe), the AISRS total score is derived by summing the score assigned to each of the 18 symptoms. Scores can range from 0 to 54, with a higher score indicating a more severe ADHD symptoms. Baseline was defined as the score at the baseline visit prior to starting dosing for Period 1 and as the last score in the 2-week placebo wash-out period for Period 2. For the statistical analyses, the average score from Day 14 and Day 21 was used.
次要结局
- Percentage of Participants With at Least a 30% Reduction From Baseline in AISRS Score(Baseline and Day 21)
- Percentage of Participants With at Least a 50% Reduction From Baseline in AISRS Score(Baseline and Day 21)
- Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score(Baseline and Day 7, Day 14, Day 21)
- Percentage of Participants Who Experience At Least One Adverse Event (AE)(Up to 7 days after last dose of study drug (Up to 63 days))
- Percentage of Participants Who Discontinue Study Drug Due to an AE(Up to last dose of study drug (Up to 56 days))
- Percentage of Participants With Clinician Global Impression Scale - Severity (CGI-S) Category Scores(Days 14-21)
- Percentage of Participants With Clinician Global Impression Scale - Improvement (CGI-I) Scores(Days 14-21)
- Change From Baseline in Epworth Sleepiness Scale (ESS) Score(Baseline and Day 7, Day 14, Day 21)
- Change From Baseline in Quick Inventory of Depression Symptomology - Clinician Rating (QIDS-C) Score(Baseline and Day 7, Day 14, Day 21)
- Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Score(Baseline and Day 7, Day 14, Day 21)
- Computerized Cognition Assessment: Cognitive Flexibility(Baseline, Day 21)
- Computerized Cognition Assessment: Composite Memory(Baseline, Day 21)
- Computerized Cognition Assessment: Executive Functioning(Baseline, Day 21)
- Computerized Cognition Assessment: Reasoning(Baseline, Day 21)
- Computerized Cognition Assessment: Sustained Attention(Baseline, Day 21)
- Computerized Cognition Assessment: Verbal Memory(Baseline, Day 21)
- Computerized Cognition Assessment: Visual Memory(Baseline, Day 21)
- Computerized Cognition Assessment: Complex Attention(Baseline, Day 21)
- Computerized Cognition Assessment: Speed of Processing(Baseline, Day 21)
- Computerized Cognition Assessment: Reaction Time(Baseline, Day 21)
- Computerized Cognition Assessment: Working Memory(Baseline, Day 21)