A 14 Week, Randomized, Placebo-Controlled Cross-Over Stud... | NCT03785223

NCT03785223

Status Module

Name	Class
Purdue Pharma, Canada	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Methylphenidate Hydrochloride Controlled-Release Capsules	Experimental	Flexibly dosed at 25-100 mg per day	Drug: Methylphenidate Hydrochloride Controlled-Release Capsules
Placebo Capsules	Placebo Comparator	1-4 capsules daily	Drug: Placebo Capsule

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Methylphenidate Hydrochloride Controlled-Release Capsules	Drug	25 mg methylphenidate hydrochloride- titrated as tolerated up to a maximum 4 capsules daily (25 mg- 100 mg total dose) At Week 0 or Week 7, dosing will start at 1 capsule/day for one week, and be titrated to 2 capsules/day for Week 2. 50 mg of methylphenidate hydrochloride per day (i.e. 2 capsules/day) is the minimum dose that must be achieved. The dose may be titrated to 75 mg/day for Week 3 and to 100 mg/day for Week 4 if participants are tolerating their current dose, are experiencing no adverse events, and have not fully responded. By Week 4 or Week 11, no further dose changes will occur.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Attention Deficit and Hyperactivity Rating Scale - 5	The ADHD-RS-5 is a scale for children and adolescents that assesses the frequency and severity of ADHD symptoms and impairments based on criteria from the Diagnostic Statistics Manual 5. The measure will be adapted for use with adults as a clinician rated scale in this study. It consists of 18 items, rated on a 4-point scale from 0 (never or rarely) to 3 (very often). The items can be summed to obtain a total score (range: 0-54), an Inattention subscore (range:0-27), and a Hyperactivity-Impulsivity subscore (range: 0-27), with higher scores indicating greater frequency and severity of symptoms.	Change from baseline to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Hamilton Anxiety Rating Scale (HAM-A)	The 14-item HAM-A was developed to assess general anxiety symptoms in a clinical population and has proven sensitive to change with treatment. It is a clinician-rated measure and will be administered by a trained, blinded rater, using the Structured Interview Guide for the HAM-A. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) are summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Outpatient men and women between 18 and 65 years who meet criteria for Current DSM-5 ADHDalone or with one of the following DSM-5 diagnoses: GAD, SAD,PD or Agoraphobia. Major Depressive Disorder or Persistent Depressive Disorder will be allowed, providing the severity is considered moderate or less, as defined by a score on the Montgomery Depressive Rating Scale-MADRS score of ≤ 25.
ADHD rating scale for DSM-5 (ADHD-5-RS) score ≥ 24.
Concomitant treatment with selective serotonin reuptake inhibitors (SSRI's), serotonin noradrenaline reuptake inhibitors (SNRI's), benzodiazepines, beta-blockers, atypical anti-psychotics, anti-epileptics is allowed, provided the dose has been stable for 8 weeks prior to study entry. Dose changes of allowed concomitant medication should be avoided during the treatment phases of the study.
The ability to comprehend and satisfactorily comply with protocol requirements.
Written informed consent given prior to entering the baseline period of the study.
All women of child bearing potential must have a negative screening visit serum or urine pregnancy test and be using adequate contraception for the duration of the study. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices or properly used barrier contraception. Additionally, the use of condoms is suggested as an adjunct to the methods previously addressed to provide additional protection against accidental pregnancy.

Exclusion Criteria:

Participants who currently fulfill criteria for a lifetime history of bipolar disorder, schizophrenia or other psychotic disorders, delirium, dementia and amnesic and other cognitive disorders, severe head injury, autism spectrum disorders, or are in a current agitated state.
Participants with a history of seizure disorders, or an unstable medical condition will also be excluded.
Participants with significant suicidal ideation (MADRS item 10 score > 3) or who have enacted suicidal behaviours within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
Current treatment with a stimulant.
A history of > 2 failed trials of adequately dosed psychostimulants for Adult ADHD.
Patients receiving current psychotherapy, including cognitive behavioural therapy for either ADHD or an anxiety disorder, within 4 weeks prior to the baseline period.
Patients who are known to be allergic to methylphenidate or components of methylphenidate hydrochloride, have known hypersensitivity or idiosyncrasy to methylphenidate hydrochloride.
Patients who have thyroid pathology, treatment of which has not been stabilized for at least 3 months.
MAO inhibitors within 3 weeks of the start of the baseline.
Individuals meeting criteria for current cannabis use disorder or substance use disorder will be excluded.
Current use of bupropion or tri-cyclic antidepressants, with the exception of clomipramine.
Current use of clonidine, modafinil or atomoxetine.
Previous intolerance or failure to respond to an adequate trial of methylphenidate hydrochloride controlled release capsules (defined as a minimum of 55mg per day for at least 4 weeks).
Patients who have a history or evidence of a medical condition that would expose them to an increase or significant adverse event or interfere with assessments of safety and efficacy during the course of the trial including: advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, or other pre-existing cardiac abnormalities or other serious cardiac problems.
Patients with a history of Glaucoma.
Sleep medications during the study period are excluded with the exception of zopiclone and zolpidem and melatonin.
Patients using any herbal psychoactive treatments, eg; St.John's Wort, Valerian, Kava Kava, or Chamomile Extract within 14 days prior to randomization.
Patients who have received electroconvulsive therapy within the previous 6 months.
Patients with any condition or on any therapy that in the investigator's opinion or as indicated in the methylphenidate hydrochlorideproduct label, that may pose a risk to the subject or interfere with the study objective.
Patients having clinically significant abnormal laboratory or ECG findings not resolved by the baseline examination.
Patients with a proximal family history of sudden, unexplained cardiac death.

ID	Term
D001289	Attention Deficit Disorder with Hyperactivity
D000098647	Generalized Anxiety Disorder
D000072861	Phobia, Social
D016584	Panic Disorder
D000379	Agoraphobia
D001008	Anxiety Disorders

ID	Term
D019958	Attention Deficit and Disruptive Behavior Disorders
D065886	Neurodevelopmental Disorders
D001523	Mental Disorders
D010698	Phobic Disorders