Pharmacokinetics of Two Extended-Release Formulations of Methylphenidate in Children With Attention Deficit Hyperactivity Disorder (ADHD)

NCT00772161 | Completed Phase 1

• 2 other identifiers: CRIT124DDE03EudraCT Number: 2008-000227-25
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to provide pharmacokinetic data for the assessment of bioequivalence of Ritalin LA formulation compared to Medikinet ret. concerning plasma levels and efficacy measures. The primary objective of the study is to determine the pharmacokinetic parameters and bioequivalence of Ritalin LA compared to Medikinet retard, both given as oral o.d. doses of 20 mg over 7 days in children with ADHD. The secondary objectives are to assess the efficacy, safety and tolerability of Ritalin LA and Medikinet retard and the association of these parameters with plasma levels.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

ADHD; Attention Deficit Disorder; Attention Deficit an Disruptive Behavior Disorders; Children; Central Nervous System Stimulants; Methylphenidate; Pharmacokinetics; Area Under Curve; Therapeutic Equivalency; Psychopharmacology

Outcome Measures

Primary Outcomes (2)

• C-max: Concentration of the Peak in the Plasma Concentration Curve

  In Visit 3 (day 7) and Visit 4 (day 14): Repeated Assessment 1:00 h before and 0:30 h, 1:15 h, 2:15 h, 3:15 h, 4:15 h, 4:50 h, 5:30 h, 6:15 h, 8:00 h after medication intake

• AUC-(0-inf): Area under the plasma concentration versus time curve extrapolated to infinity time

  In Visit 3 (day 7) and Visit 4 (day 14): Repeated Assessment 1:00 h before and 0:30 h, 1:15 h, 2:15 h, 3:15 h, 4:15 h, 4:50 h, 5:30 h, 6:15 h, 8:00 h after medication intake

Secondary Outcomes (4)

• Efficacy measure: SKAMP Combined rating, SKAMP-Attention subscale, SKAMP-Deportment subscale in a laboratory classroom setting.

  In Visit 3 (day 7) and Visit 4 (day 14): Repeated Assessment at 0:25 h before and 0:50 h, 1:50 h, 2:50 h, 3:50 h, 5:50 h, 7:20 h after medication intake

• Efficacy measure: Nisonger Child Behavior Rating Form - typical IQ Version (NCBRF-TIQ)from the primary caregiver.

  Visite 2 ( Baseline, day 0), Visit 3 (day 7), Visit 4 (day 14)

• Clinical Global Impressions - Severity of Illness scale (CGI-S) and Clinical Global Impressions - Improvement scale (CGI-I) by a child & adolescent psychiatrist

  Visite 2 ( Baseline, day 0), Visit 3 (day 7), Visit 4 (day 14)

• Assessment of Adverse Events

  Visite 2 (Baseline, day 0), Visit 3 (day 7) and Visit 4 (day 14)

Study Arms (2)

Sequence 1

EXPERIMENTAL

First treatment week (day 1 to day 7) 20mg Ritalin LA; second treatment week (day 8 to day 14) 20mg Medikinet retard.

Drug: Methylphenidate

Sequence 2

EXPERIMENTAL

First treatment week (day 1 to day 7) 20mg Medikinet retard; second treatment week (day 8 to day 14) 20mg Ritalin LA.

Drug: Methylphenidate

Interventions

Methylphenidate DRUG

Comparison of two extended-release formulations of 20mg Methylphenidate in a cross-over design.

Also known as: Ritalin LA, Medikinet retard

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 8 Years - 14 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The patient and the parents/authorized legal representatives must understand the nature of the study and be able to comply with protocol requirements.
• Male patients aged 8-14 with Tanner stages 0 to 2 and a BMI between the 10th and 90th age percentile
• Patients having a diagnosis of ADHD of any type according to DSM-IV criteria, as established by history, psychiatric examination and a structured diagnostic interview (Kiddie-SADS-Present and Lifetime Version)
• Patients, whose symptoms are adequately controlled by a stable and well-tolerated dose of immediate release methylphenidate equivalent of 15 mg to 30 mg for at least one month before screening.
• Patients with parents or a legal guardian, who will give written informed consent for the child to participate in the study. Additionally, assent to participate must be obtained from all children entering the study. Assent will be documented by the child's signature on the consent form.
• Health status: Patients must have no clinically significant diseases or clinically significant abnormal laboratory values as assessed during medical history and physical exam.
• Patients meeting minimum intelligence requirements: In the opinion of the investigator the patient must generally be functioning at age-appropriate levels academically, which should take into account any prior cognitive or academic testing (basic knowledge of reading, writing and calculating).
• Patients already receiving behavioral therapies for ADHD may continue to do so during the course of the trial.

You may not qualify if:

• Patients with co-morbid psychiatric conditions with symptoms requiring current pharmacological treatment (e.g. major depression, psychosis).
• Patients with co-morbid psychiatric or somatic conditions that may contraindicate treatment or confound efficacy or safety assessments.
• Patients who are taking any concomitant medications likely to interfere with the study drug or confound efficacy or safety assessments, e.g. Tricyclic antidepressants, SSRIs except Fluoxetine, bupropion, clonidine, buspirone 2 weeks before randomization; Atomoxetine 2 weeks before randomization; Fluoxetine or antipsychotics 1 month before randomization; Pemoline and amphetamines 1 week before randomization.
• Patients with a known non-response to methylphenidate.
• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
• Patients who are judged by the investigator as likely to be non-compliant with study procedures, including those with a suspected history of substance abuse, or patients living with a person diagnosed with a substance abuse disorder.
• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
• Patients with warnings, mentioned in the German Basic Prescribing Information of Ritalin LA (SmPC in the current version) or Medikinet retard (SmPC in the current version): anorexia, severe depression, anxiety disorder, Gilles de la Tourette-Syndrome, other tic disorder, hypertension, occlusive arterial diseases, severe stenocardia, tachycardiac arrhythmia, stroke, hyperthyroidism, increased intra-ocular pressure, hypertrophy of the prostate, known hypersensitivity to sympathomimetics, MAO-inhibitors.
• Patients with a history of seizure disorder.
• History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.

Sponsors & Collaborators

• University Hospital Freiburg: lead
• Novartis: collaborator

Study Sites (1)

University Hospital Freiburg, Dep. for Child & Adolescent Psychiatry

Freiburg im Breisgau, D-79104, Germany

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christian Fleischhaker, MD

  Universitätsklinikum Freiburg

  STUDY DIRECTOR

• Eberhard Schulz, Prof. Dr.

  Universitätsklinikum Freiburg

  PRINCIPAL INVESTIGATOR

• Klaus Hennighausen, MD

  University Hospital Freiburg, Dep. for Child & Adoslecent Psychiatry

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 14, 2008
• First Posted: October 15, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: January 21, 2009

Record last verified: 2009-01

Locations

DE (1)