Attention Deficit Hyperactivity DisorderPhase 1/2MPH-KineticsNCT00772161
Pharmacokinetics of Two Extended-Release Formulations of Methylphenidate in Children With Attention Deficit Hyperactivity Disorder (ADHD)
A Phase 1/2 study testing Methylphenidate in people with Attention Deficit Hyperactivity Disorder, run by University Hospital Freiburg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 14 years, men only
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- Methylphenidate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2008to Dec 2008
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 14 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Freiburg, Dep. for Child & Adolescent Psychiatry
Freiburg im Breisgau, D-79104
About this study
Official title: A Single-Center, Single-Blind, Randomized, Oral Dose Cross-Over Study in Prepuberal Boys With ADHD to Investigate Efficacy and Bioequivalence of 20 mg Ritalin LA Compared to 20 mg Medikinet Retard After Treatment With o.d. Doses Over 7 Days Each.
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.
Read the detailed description
Study Design
This is a single center, Phase I, prospective, randomized, single blind, two-treatment cross-over study. 24 patients will be enrolled. Study duration for each patient is approximately 4 weeks (from screening/inclusion). Based on the assumption of 5 months recruitment, the total study duration will be approximately 6 month.
Target Population
A number of 24 prepubertal boys aged 8 - 14 years with Diagnosis of ADHD according to DSM IV will be enrolled in this study to ensure that 18 subjects will complete all assessments. The prepuberal status will be determined by Tanner stages ≤ 2. Diagnosis will be confirmed by the K-SADS-PL.
Patients will only be allowed to enter the trial if subject and subject´s parents/legal guardians provide informed consent about participation (following full explanation of the trial) and a written informed consent document is signed. In addition, it has to be verified by a physician that the patient meets all of the Inclusion Criteria and none of the Exclusion Criteria.
Study Treatment
Study medications will be either Ritalin LA 20 mg or Medikinet ret. 20 mg. Patients with a pre-treatment of psychotropic drugs other than Methylphenidate will have an individual washout period before inclusion to the study. This individual washout period will last 5 elimination half-life of the taken drug.
After randomization the patients will enter a 2 week treatment phase with a crossover at day 8. Patients randomized to Sequence 1 will be treated with Ritalin LA for the first week (day 1 to day 7) and with Medikiniet ret. for the second week (day 8 to day 14); patients randomized to Sequence 2 will be treated with Medikinet ret. for the first week (day 1 to day 7) and with Ritalin LA for the second week (day 8 to day 14). The study population will be randomized equally to the Sequence 1 or Sequence 2 group at Visit 2. The study ends 5 weeks after enrollment of the last patient (total study end).
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- Methylphenidate
- Keywords
- ADHD, Attention Deficit Disorder, Attention Deficit an Disruptive Behavior Disorders, Children, Central Nervous System Stimulants, Methylphenidate, Pharmacokinetics, Area Under Curve, Therapeutic Equivalency, Psychopharmacology
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called Ritalin LA, Medikinet retard
Comparison of two extended-release formulations of 20mg Methylphenidate in a cross-over design.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
C-max: Concentration of the Peak in the Plasma Concentration Curve
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: Visite 2 ( Baseline, day 0), Visit 3 (day 7), Visit 4 (day 14)
Assessment of Adverse Events
Measured: Visite 2 (Baseline, day 0), Visit 3 (day 7) and Visit 4 (day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Investigators
- Christian Fleischhaker, MD, Study director, University Hospital FreiburgEberhard Schulz, Prof. Dr., Principal investigator, University Hospital FreiburgKlaus Hennighausen, MD, Study chair, University Hospital Freiburg, Dep. for Child & Adoslecent Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00772161
- Sponsor's protocol ID
- CRIT124DDE03
- Other IDs
- EudraCT Number: 2008-000227-25
- Acronym
- MPH-Kinetics
- Status last verified
- Jan 2009
- First submitted
- 14 Oct 2008
- Last updated
- 21 Jan 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Center, Single-Blind, Randomized, Oral Dose Cross-Over Study in Prepuberal Boys With ADHD to Investigate Efficacy and Bioequivalence of 20 mg Ritalin LA Compared to 20 mg Medikinet Retard After Treatment With o.d. Doses Over 7 Days Each.
- ClinicalTrials.gov ID
- NCT00772161
- Acronym / sponsor ID
- MPH-Kinetics / CRIT124DDE03
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Oct 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 15 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Design
This is a single center, Phase I, prospective, randomized, single blind, two-treatment cross-over study. 24 patients will be enrolled. Study duration for each patient is approximately 4 weeks (from screening/inclusion). Based on the assumption of 5 months recruitment, the total study duration will be approximately 6 month.
Target Population
A number of 24 prepubertal boys aged 8 - 14 years with Diagnosis of ADHD according to DSM IV will be enrolled in this study to ensure that 18 subjects will complete all assessments. The prepuberal status will be determined by Tanner stages ≤ 2. Diagnosis will be confirmed by the K-SADS-PL.
Patients will only be allowed to enter the trial if subject and subject´s parents/legal guardians provide informed consent about participation (following full explanation of the trial) and a written informed consent document is signed. In addition, it has to be verified by a physician that the patient meets all of the Inclusion Criteria and none of the Exclusion Criteria.
Study Treatment
Study medications will be either Ritalin LA 20 mg or Medikinet ret. 20 mg. Patients with a pre-treatment of psychotropic drugs other than Methylphenidate will have an individual washout period before inclusion to the study. This individual washout period will last 5 elimination half-life of the taken drug.
After randomization the patients will enter a 2 week treatment phase with a crossover at day 8. Patients randomized to Sequence 1 will be treated with Ritalin LA for the first week (day 1 to day 7) and with Medikiniet ret. for the second week (day 8 to day 14); patients randomized to Sequence 2 will be treated with Medikinet ret. for the first week (day 1 to day 7) and with Ritalin LA for the second week (day 8 to day 14). The study population will be randomized equally to the Sequence 1 or Sequence 2 group at Visit 2. The study ends 5 weeks after enrollment of the last patient (total study end).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Experimental | Drug: MethylphenidateFirst treatment week (day 1 to day 7) 20mg Ritalin LA; second treatment week (day 8 to day 14) 20mg Medikinet retard. |
| Sequence 2 | Experimental | Drug: MethylphenidateFirst treatment week (day 1 to day 7) 20mg Medikinet retard; second treatment week (day 8 to day 14) 20mg Ritalin LA. |
Who may qualify
- Ages
- 8 to 14 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylphenidateAlso: Ritalin LA, Medikinet retardComparison of two extended-release formulations of 20mg Methylphenidate in a cross-over design. | Drug | Sequence 1, Sequence 2 |
Primary outcome
C-max: Concentration of the Peak in the Plasma Concentration Curve
Time frame: 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
Time frame: 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
4 secondary outcomes
Efficacy measure: SKAMP Combined rating, SKAMP-Attention subscale, SKAMP-Deportment subscale in a laboratory classroom setting.
Time frame: 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.
Time frame: 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
Time frame: Visite 2 ( Baseline, day 0), Visit 3 (day 7), Visit 4 (day 14)
Assessment of Adverse Events
Time frame: Visite 2 (Baseline, day 0), Visit 3 (day 7) and Visit 4 (day 14)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Fleischhaker, MD study director
University Hospital Freiburg
Eberhard Schulz, Prof. Dr. principal investigator
University Hospital Freiburg
Klaus Hennighausen, MD study chair
University Hospital Freiburg, Dep. for Child & Adoslecent Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Methylphenidate in people with Attention Deficit Hyperactivity Disorder, run by University Hospital Freiburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
C-max: Concentration of the Peak in the Plasma Concentration Curve (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2009.