Clinical trial NCT00610441: Dose Finding Study in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)(174007/P05805/MK-8777-003)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: randomized
double blind
placebo controlled
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-02-08
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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;

Primary outcomes:
measure: Change From Baseline in Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Investigator Symptom Rating Scale (AISRS) Score
timeFrame: Baseline (BL) and Day 7, Day 14, Day 21
Secondary outcomes:
measure: Percentage of Participants With at Least a 30% Reduction From Baseline in AISRS Score
timeFrame: Baseline and Day 21
measure: Percentage of Participants With at Least a 50% Reduction From Baseline in AISRS Score
timeFrame: Baseline and Day 21
measure: Percentage of Participants Who Experience At Least One Adverse Event (AE)
timeFrame: Up to 7 days after last dose of study drug (Up to 63 days)
measure: Percentage of Participants Who Discontinue Study Drug Due to an AE
timeFrame: Up to last dose of study drug (Up to 56 days)
measure: Percentage of Participants With Clinician Global Impression Scale - Severity (CGI-S) Category Scores
timeFrame: Days 14-21
measure: Percentage of Participants With Clinician Global Impression Scale - Improvement (CGI-I) Scores
timeFrame: Days 14-21
measure: Change From Baseline in Epworth Sleepiness Scale (ESS) Score
timeFrame: Baseline and Day 7, Day 14, Day 21
measure: Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score
timeFrame: Baseline and Day 7, Day 14, Day 21
measure: Change From Baseline in Quick Inventory of Depression Symptomology - Clinician Rating (QIDS-C) Score
timeFrame: Baseline and Day 7, Day 14, Day 21
measure: Change From Baseline in Time-Sensitive ADHD Symptom Scale (TASS) Score
timeFrame: Baseline and Day 7, Day 14, Day 21
measure: Computerized Cognition Assessment: Cognitive Flexibility
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Complex Attention
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Composite Memory
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Executive Functioning
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Speed of Processing
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Reaction Time
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Reasoning
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Sustained Attention
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Verbal Memory
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Visual Memory
timeFrame: Baseline, Day 21
measure: Computerized Cognition Assessment: Working Memory
timeFrame: Baseline, Day 21
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: