A 14 Week, Randomized, Placebo-Controlled Cross-Over Study of Methylphenidate Hydrochloride Controlled Release Capsules in Adult ADHD With and Without Anxiety Disorder Comorbidity

NCT03785223 | Completed Phase 4

• 1 other identifier: 5748
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Other psychiatric disorders, including anxiety, often co-occur with adult ADHD; with 85% of ADHD patients having at least one other psychiatric condition. The presence of a co-occurring anxiety disorder has been associated with additive clinical effects, leading to more global impairment, poorer outcome, greater resistance to treatment and increased costs of illness. Stimulants are effective first-line treatments for adult ADHD patients, however the literature has mostly examined these treatments in pure ADHD populations (i.e. without other psychiatric disorders). Thus, there is little information to guide physicians in making treatment decisions for patients with ADHD and a co-occurring condition. This trial aims to evaluate the efficacy and safety of methylphenidate hydrochloride controlled release capsules (Foquest) in treating adults aged 18-65 years with DSM-5 ADHD with and without a co-occurring anxiety disorder.The study uses a 14-week, randomized, placebo-controlled, cross-over design.

Conditions

Attention Deficit Hyperactivity Disorder; Generalized Anxiety Disorder; Social Anxiety Disorder; Panic Disorder; Agoraphobia

Keywords

ADHD; Anxiety Disorders; Stimulants; Methylphenidate

Outcome Measures

Primary Outcomes (1)

• 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 (21)

• Hamilton Anxiety Rating Scale (HAM-A)

  Change from baseline to Week 12

• Clinical Global Impression - Severity (CGI-S)

  Change from baseline to Week 12

• Clinical Global Impression - Improvement (CGI-I)

  Change from baseline to Week 12

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  Change from baseline to Week 12

• Barkley Adult ADHD Rating Scale (BAARS-IV)

  Change from baseline to Week 12

Study Arms (2)

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

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.

Also known as: Foquest

Methylphenidate Hydrochloride Controlled-Release Capsules

Placebo Capsule DRUG

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. 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.

Placebo Capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• McMaster University: lead
• Purdue Pharma, Canada: collaborator

Study Sites (1)

MacAnxiety Research Center

Hamilton, Ontario, L8S 1B7, Canada

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Generalized Anxiety Disorder; Phobia, Social; Panic Disorder; Agoraphobia; Anxiety Disorders

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Phobic Disorders

Study Officials

• Michael Van Ameringen, MD, FRCPC

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 24, 2018
• Study Start: April 20, 2019
• Primary Completion: September 30, 2022
• Study Completion: October 31, 2022
• Last Updated: October 26, 2023

Record last verified: 2023-10

Locations

CA (1)