Dose Finding Study in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)(174007/P05805/MK-8777-003)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Attention Deficit Hyperactivity Disorder

Treatments: Drug: MK-8777; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00610441

174007 (Other Identifier)

P05805

Details and patient eligibility

About

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.

Enrollment: 67 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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67 participants in 4 patient groups, including a placebo group

MK-8777 FD→PBO

Experimental group

Description:

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).

Treatment:

Drug: Placebo

Drug: MK-8777

PBO→MK-8777 FD

Experimental group

Description:

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).

Treatment:

Drug: Placebo

Drug: MK-8777

MK-8777 RD→PBO

Experimental group

Description:

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).

Treatment:

Drug: Placebo

Drug: MK-8777

PBO→MK-8777 RD

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

Drug: MK-8777