Clinical trial NCT02477748: The MEASURE Study - A Phase 3 Study of MDX 1400 mg Daily Compared With Placebo in Adults With ADHD
Official title: A 10-week Randomized, Multicenter, Double-blind, Parallel, Fixed-dose Study of MDX (Metadoxine Immediate-release/Slow-release, Bilayer Tablet) 1400 mg Compared With Placebo in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Lead sponsor: Alcobra Ltd.
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 283
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multi-center, randomized, double-blind, placebo-controlled, phase 3 study of MDX (1400 mg daily) for 10 weeks compared with placebo in adults with ADHD.

The study will be comprised of Screening, Washout (if required), Treatment (total of 10 weeks) and Follow-up periods. Approximately 750 patients will be enrolled and undergo initial eligibility assessments.

Detailed description: * A 10-week randomized, multi-center, double-blind, placebo-controlled, phase 3 study of MDX (1400 mg daily) for 10 weeks compared with placebo in adults with ADHD.
* The study will be comprised of Screening, Washout (if required), Treatment (total of 10 weeks) and Follow-up periods. Approximately 750 patients will be enrolled and undergo initial eligibility assessments.
* Subjects requiring a washout will undergo a Washout period where ADHD medication is discontinued (21 days for atomoxetine, 14 days for other ADHD medications). These subjects will have an Interim Visit (off drug) on or about Day -10 (Day -10 to Day -3) for CAARS-Inv assessment at the end of the Washout period.
* Subjects will be randomly assigned to placebo/MDX for a total treatment duration of up to ten weeks.

There will be a one week Follow-up period after the last dose of study treatment or early termination.

Eligibility criteria: Inclusion Criteria:

1. Subject is a man or a non-pregnant, non-lactating woman 18 to 55 years of age, inclusive, at the Screening visit.
2. Subject has a diagnosis of ADHD based on criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM5) as assessed by the Adult ADHD Clinician Diagnostic Scale, (ACDS Version 1.2) modified for DSM-IV and DSM5 diagnoses; a diagnosis of ADHD not otherwise specified is unacceptable.
3. Male and Female subjects of childbearing potential must agree to use an effective contraceptive throughout the study
4. Subject is able to attend the clinic regularly and reliably.
5. Subject is able to swallow tablets and capsules.
6. Subject is able to understand, read, write, and speak the local language fluently to complete the study-related materials.
7. Subject is able to understand and sign an informed consent form to participate in the study.

Exclusion criteria

1. Subject has any current major psychiatric condition (e.g., schizophrenia, bipolar or personality disorder) or autism spectrum disorder.
2. Subject has any clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation.
3. Subject has used an investigational medication/treatment or was enrolled in another clinical trial in the 30 days before the Screening visit.
4. Subject has used any medication or food supplement that the investigator or the medical monitor consider unacceptable during the 14-day period before the Baseline visit.
5. Subject's alcohol and caffeine intake will be assessed.
6. Subject has current suicidality, defined as active ideation, intent or plan, or any significant lifetime suicidal behavior (actual attempt, aborted attempt, interrupted attempt, or act or preparation towards imminently making a suicide attempt). Subjects exhibiting history (within previous 12 months) of non-suicidal self-injurious behavior will be excluded.
7. Subject has taken any prescription or non-prescription medication for ADHD during the 14 days (or 21 days for atomoxetine) before the Baseline visit. Subjects will not be allowed to take any other medications for ADHD besides the study medication (when prescribed) after the washout period and for the duration of the study, up to and including the safety Follow-up visit. (Other ADHD medications should NOT be prescribed to subjects before completion of the Follow-up visit or Early Termination Visit).
8. Subject is significantly visually impaired to an extent that is not able to be corrected by prescription glasses or contact lenses.
9. Subject is closely related to the sponsor, investigator, or study staff. Eligibility of subjects with any relationship to the sponsor, investigator, or study staff will be discussed with the medical monitor before study entry, and the medical monitor will decide on the eligibility of these cases.
10. Subject has previously been enrolled in an MDX clinical trial.
11. Subject lives in the same household as another subject in this clinical trial or in another on-going trial with MDX. Subject lives in the same household as someone who has previously participated in a trial with MDX.
12. Subject has any condition that, in the principal investigator's opinion, would place the subject at risk or influence the conduct of the study or interpretation of results, including (but not limited to) abnormally low intellectual capacity as judged by the investigator.
13. Subject cannot fully comprehend the implications of the protocol, cannot comply with its requirements, or is incapable of following the study schedule for any reason.
14. Subject is pregnant, lactating, or using an inadequate contraceptive method. Complete entry criteria will be reviewed and evaluated individually by a protocol trained delegate.

Primary outcomes:
measure: 18-item total ADHD symptom score of the Conners Adult ADHD Rating Scale:O-SV (with the investigator as observer) with adult ADHD prompts (CAARS investigator).
timeFrame: 10 weeks
Secondary outcomes:
measure: Questionnaires of Clinical Global Severity of Illness (CGI-S) and Clinical Global Improvement (CGI-I).
timeFrame: 10 weeks
measure: Adult ADHD Self Report Scale (ASRS-Self) v1.1 Symptom Checklist - expanded version
timeFrame: 10 weeks
measure: Test of Variables of Attention (TOVA)
timeFrame: 10 weeks
measure: Test of Variables of Attention (TOVA)
timeFrame: 10 weeks
measure: Test of Variables of Attention (TOVA)
timeFrame: 10 weeks
measure: Test of Variables of Attention (TOVA)
timeFrame: 10 weeks
measure: Test of Variables of Attention (TOVA)
timeFrame: 10 weeks
measure: Test of Variables of Attention (TOVA)
timeFrame: 10 weeks
measure: Safety as assessed by adverse events (AEs)
timeFrame: 10 weeks
measure: Safety as assessed by body temperature measurements
timeFrame: 10 weeks
measure: Safety as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: 10 weeks
measure: Safety as assessed by laboratory tests; blood and urine
timeFrame: 10 weeks
measure: Safety as assessed by neurological evaluation
timeFrame: 10 weeks
measure: Safety as assessed by Electrocardiogram (ECG) test
timeFrame: 10 weeks
measure: Safety as assessed by physical examinations
timeFrame: 10 weeks
measure: Safety as assessed by discontinuations due to AEs
timeFrame: 10 weeks
measure: Safety as assessed by heart rate measurements
timeFrame: 10 weeks
measure: Safety as assessed by respiratory rate measurements
timeFrame: 10 weeks
measure: Safety as assessed by supine blood pressure
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex, Inc.
state: Alabama
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers
state: Colorado
city: Cromwell
country: United States
facility: Connecticut Clinical Research
state: Connecticut
city: New London
country: United States
facility: Coastal Connecticut Research
state: Connecticut
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Orlando
country: United States
facility: CNS Healthcare
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Alpharetta
country: United States
facility: Institute for Advanced Medical Research
state: Georgia
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research
state: Indiana
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Rochester Hills
country: United States
facility: Rochester Center For Behavioral Medicine
state: Michigan
city: St. Charles
country: United States
facility: St. Charles Psychiatric Associates - Midwest Research Group
state: Missouri
city: Lincoln
country: United States
facility: Premier Psychiatric Research Institute
state: Nebraska
city: Cherry Hill
country: United States
facility: Center for Emotional Fitness
state: New Jersey
city: Princeton
country: United States
facility: Global Medical Institutes, LLC, Princeton Medical Institute
state: New Jersey
city: New York
country: United States
facility: The Medical Research Network
state: New York
city: Raleigh
country: United States
facility: Richard H Weisler, MD, PA
state: North Carolina
city: Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Oklahoma
country: United States
facility: Village Clinical Research Inc
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Carolina Clinical Research, Inc.
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions
state: Tennessee
city: Austin
country: United States
facility: BioBehavioral Research of Austin at Specialty Clinic of Austin
state: Texas
city: Houston
country: United States
facility: Bayou City Research
state: Texas
city: Salt Lake City
country: United States
facility: Psychiatric & Behavioral Solutions
state: Utah
city: Herndon
country: United States
facility: NeuroScience, Inc. (NSI)
state: Virginia
city: Seattle
country: United States
facility: Summit Research Network(Seattle)LLC
state: Washington
city: Middleton
country: United States
facility: Dean Foundation - Middleton
state: Wisconsin
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petah Tiqva
country: Israel
facility: Geha Medical Centre
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey Newcorn, MD
role: PRINCIPAL_INVESTIGATOR
References: