Conduct DisorderPhase 2NCT00676429
Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders
A Phase 2 study testing Ziprasidone Hydrochloride in people with Conduct Disorder and Oppositional Defiant Disorder, run by University Hospital Freiburg at 1 site in Germany.
Trial summary
To investigate and compare the efficacy, safety and tolerability of ziprasidone versus placebo in the treatment of conduct disorder (CD), oppositional defiant disorder (ODD) and disruptive behavior disorder not otherwise specified (DBD-NOS) of older children and adolescents in an outpatient setting. Read more about this study
- Who is it for?
- Ages 7 to 17 years
- Conditions the study is for
- Conduct Disorder, Oppositional Defiant Disorder
- What is being tested?
- Ziprasidone Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2006to Jun 2008
- Phase
- Phase 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 7 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- The subject and the authorized legal representative must understand the nature of the study and be able to comply with protocol requirements. The representative must sign an Informed Consent Document and the subject must provide Written Assent.
- The subject (male or female) must be between 7-17 (inclusive) years of age at screening.
- The subject must have a primary diagnosis of Conduct Disorder [CD] (312.8), Oppositional Defiant Disorder [ODD] (313.81) or Disruptive Behavior Disorder not otherwise specified [DBD-NOS] (312.9) as defined by DSM-IV criteria and confirmed by the Kiddie-SADS-PL.
- At the screening visit (Visit 1), subjects must have a score of 21 or more on the sum of the scales for conduct problems and for oppositional behaviour in the NCBRF-TIQ.
- In the investigator's opinion, the subject must be likely to benefit from the therapy.
- The subject is willing and able to discontinue any medications that are prohibited in this study (see Concomitant Medications table, Section 3.5.1). Any such medications must be discontinued at least 5 half-lives prior to the administration of double-blinded study medication.
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- Patients who are receiving prohibited medications are to be considered for the protocol only If discontinuation of the medication does not compromise the welfare of the patient and/or alternative medication that is allowed by the protocol is available and appropriate for the patient. Psychotropic medications should be tapered down per accepted medical practice and the specific package insert instead of being abruptly discontinued.
- Females of childbearing potential may be included provided that they are not pregnant, not nursing, and are practicing effective contraception and meet all of the following criteria:
- Are instructed and agree to avoid pregnancy during the study.
- Have a negative pregnancy test (β-HCG) at screening and Visit 2.
- Use one of the following birth control methods:
- an oral contraceptive agent, an intrauterine device (ILTD), an implantable contraceptive (e.g. Norplant), transdermal hormonal contraceptive (e.g. Ortho-Evra), or an injectable contraceptive (e.g. Depo-Provera) for at least one month prior to entering the study and will continue its use throughout the study; or
- a barrier method of contraception, e.g., condom and / or diaphragm with spermicide while participating in the study.
- abstinence for at least 3 months before the start of the study and intention to abstain from sexual activity during the study period.
- Subjects must have an IQ > 55 best tested with the HAWIK-III, alternatively with the CFT-20 or K-ABC.
Who cannot join
None listed.
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: Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders in Children and Adolescents - a Placebo Controlled, Randomized, Double Blind Clinical Trial
To investigate and compare the efficacy, safety and tolerability of ziprasidone versus placebo in the treatment of conduct disorder (CD), oppositional defiant disorder (ODD) and disruptive behavior disorder not otherwise specified (DBD-NOS) of older children and adolescents in an outpatient setting.
Conduct and other behavior disorders are some of the most common forms of psychopathology in children and adolescents. The main characteristic of these disorders is a repetitive and persistent pattern of antisocial, aggressive or defiant behavior that involves major violations of age-appropriate expectations or norms. According to the guidelines of the German Society for Child \& Adolescent Psychiatry \& Psychotherapy (Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie und -psychotherapie DGKJPP), the European Society for Child and Adolescent Psychiatry (ESCAP), and the American Academy of Child and Adolescent Psychiatry (AACAP) currently no standard pharmacotherapy is established and recommended for children and adolescents. However Risperidone has been shown to be effective in the treatment of patients with disruptive behavior disorders and below average IQ.
Read the detailed description
Trial Design:
A placebo-controlled, parallel-group, randomized, double-blind, single center design that includes a 3-weekly baseline period for finding the best individual dose, a 6-weeks treatment period and a 2-weeks washout period.
Study Agent / Placebo - Dosage and Route of Administration:
Study medication will first be dispensed at Visit 2 (day 1). Treatment assignments will be made in accordance with the randomization sequence. At each medication visit (Visit 2 to Visit 7), subjects will receive one bottle for the following week (Visit 2 to Visit 4) resp. the following two weeks (Visit 5 to Visit 7). Only qualified personnel may dispense study medication.
The study population will be randomized equally to the verum or placebo group at Visit 2. All patients will receive an initial oral course starting with 5mg/d Ziprasidone Hydrochloride or placebo for patients with a body weight ≤ 50 kg and 10 mg/d Ziprasidone Hydrochloride or placebo for patients with a body weight > 50 kg for the first week in the study.
At Visit 3 the therapist can increase the dose to the double of the initial dose according to clinical response and tolerability. At Visit 4 the dose can be increased to the double of the last dose or reduced to the initial dose. At Visit 5 the most effective and best tolerated dose will be given for the 6 week fixed dose phase of the trial. Therefore the maximum daily dose is 20 mg (patients with body weight ≤ 50 kg) or 40 mg (patients with body weight > 50 kg). The total dose will be split and the half-dose will be given twice a day (morning and evening).
Planned Study Time Schedule:
The study ends 11 weeks after enrollment of the last patient (total study end). Study duration for each patient is 11 weeks (from inclusion) until the last visit (close-out visit). Patients with a pre-treatment of psychotropic drugs 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 3 week dose escalation phase with weekly visits. Then a 6 week stable drug dose phase will follow with visits every second week, followed by a two week washout period and a final visit.
Statistics:
Sample size calculation:
Sample size calculation is based on the assumption that treatment with Ziprasidone will show an effect size of ES=1 compared to treatment with placebo. In order to demonstrate this difference at a significance level of 5% and a power of 80%, 17 patients per group are required, and a drop-out rate of approximately 8 patients per group (with no data available to be analyzed according to the intention-to-treat principle) must be accounted for.
Analysis of efficacy:
The trial will be analyzed according to the intention-to-treat principle. The effect of treatment with Ziprasidone will be assessed by analyzing changes in the score of the scale described above. Changes calculated from the evaluations before and after treatment will be analyzed by means of analysis of covariance, considering the baseline measurement as a covariate. The difference between treatment groups will be estimated with a 95% confidence interval and will be tested within this model by the corresponding two-sided test at the 5% level of significance.
Analysis of safety:
Safety analyses will be performed for patients who received at least one dose of the investigational drug. Rates of adverse events and of serious adverse events will be calculated with corresponding 95% confidence intervals.
- Conditions
- Conduct Disorder, Oppositional Defiant Disorder
- Being tested
- Ziprasidone Hydrochloride, Placebo
- Medical subject headings
- Conduct Disorder, Oppositional Defiant Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ziprasidone HydrochlorideDrug
Also called Zeldox 10mg/ml Suspension zum Einnehmen
Ziprasidone Hydrochloride oral solution, individual titration 5 mg o.d. or 10 mg to 40 mg b.i.d
PlaceboDrug
Also called Placebo Suspension zum Einnehmen
Placebo as oral solution, individually titrated
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Ziprasidone Hydrochloride oral solution with individual titration from 5 mg to 40 mg per day Receives: Drug: Ziprasidone Hydrochloride |
| 2 | Placebo comparator | Placebo oral solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nisonger Child Behavior Rating Form for typical IQ (NCBRF-TIQ): Combined subscales "Conduct Problem" and "Oppositional Behavior"
Measured: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Secondary outcomes (5)
Assessment of the safety and tolerability by adverse event documentation.
Measured: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Assessment of the efficacy by the Clinical Global Impressions-Severity of Illness scale (CGI-S) and the Global Impressions-Improvement scale (CGI-I).
Measured: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Correlation between dosage, efficacy and adverse events.
Measured: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Ziprasidone serum levels
Measured: Visit 5 (week 3) and Visit 8 (week 8)
Correlation between serum level, efficacy and adverse events
Measured: Visit 5 (week 3) and Visit 8 (week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2008 (estimated)
- Study startJul 2006
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Conduct 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Investigators
- Eberhard Schulz, MD, Principal investigator, University Hospital Freiburg, Dep. for Child & Adolescent PsychiatryChristian Fleischhaker, MD, Study chair, University-Hospital Freiburg, Dep. for Child & Adolescent PsychiatryKlaus Hennighausen, MD, Study director, University Hospital Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00676429
- Sponsor's protocol ID
- NRA1280023
- Other IDs
- EudraCT: 2006-002207-13
- Status last verified
- Nov 2008
- First submitted
- 9 May 2008
- Last updated
- 18 Nov 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders in Children and Adolescents - a Placebo Controlled, Randomized, Double Blind Clinical Trial
- ClinicalTrials.gov ID
- NCT00676429
- Acronym / sponsor ID
- NRA1280023
- Conditions
- Conduct Disorder, Oppositional Defiant Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Jul 2006
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 13 May 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.
To investigate and compare the efficacy, safety and tolerability of ziprasidone versus placebo in the treatment of conduct disorder (CD), oppositional defiant disorder (ODD) and disruptive behavior disorder not otherwise specified (DBD-NOS) of older children and adolescents in an outpatient setting.
Conduct and other behavior disorders are some of the most common forms of psychopathology in children and adolescents. The main characteristic of these disorders is a repetitive and persistent pattern of antisocial, aggressive or defiant behavior that involves major violations of age-appropriate expectations or norms. According to the guidelines of the German Society for Child \& Adolescent Psychiatry \& Psychotherapy (Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie und -psychotherapie DGKJPP), the European Society for Child and Adolescent Psychiatry (ESCAP), and the American Academy of Child and Adolescent Psychiatry (AACAP) currently no standard pharmacotherapy is established and recommended for children and adolescents. However Risperidone has been shown to be effective in the treatment of patients with disruptive behavior disorders and below average IQ.
Detailed description
Trial Design:
A placebo-controlled, parallel-group, randomized, double-blind, single center design that includes a 3-weekly baseline period for finding the best individual dose, a 6-weeks treatment period and a 2-weeks washout period.
Study Agent / Placebo - Dosage and Route of Administration:
Study medication will first be dispensed at Visit 2 (day 1). Treatment assignments will be made in accordance with the randomization sequence. At each medication visit (Visit 2 to Visit 7), subjects will receive one bottle for the following week (Visit 2 to Visit 4) resp. the following two weeks (Visit 5 to Visit 7). Only qualified personnel may dispense study medication.
The study population will be randomized equally to the verum or placebo group at Visit 2. All patients will receive an initial oral course starting with 5mg/d Ziprasidone Hydrochloride or placebo for patients with a body weight ≤ 50 kg and 10 mg/d Ziprasidone Hydrochloride or placebo for patients with a body weight > 50 kg for the first week in the study.
At Visit 3 the therapist can increase the dose to the double of the initial dose according to clinical response and tolerability. At Visit 4 the dose can be increased to the double of the last dose or reduced to the initial dose. At Visit 5 the most effective and best tolerated dose will be given for the 6 week fixed dose phase of the trial. Therefore the maximum daily dose is 20 mg (patients with body weight ≤ 50 kg) or 40 mg (patients with body weight > 50 kg). The total dose will be split and the half-dose will be given twice a day (morning and evening).
Planned Study Time Schedule:
The study ends 11 weeks after enrollment of the last patient (total study end). Study duration for each patient is 11 weeks (from inclusion) until the last visit (close-out visit). Patients with a pre-treatment of psychotropic drugs 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 3 week dose escalation phase with weekly visits. Then a 6 week stable drug dose phase will follow with visits every second week, followed by a two week washout period and a final visit.
Statistics:
Sample size calculation:
Sample size calculation is based on the assumption that treatment with Ziprasidone will show an effect size of ES=1 compared to treatment with placebo. In order to demonstrate this difference at a significance level of 5% and a power of 80%, 17 patients per group are required, and a drop-out rate of approximately 8 patients per group (with no data available to be analyzed according to the intention-to-treat principle) must be accounted for.
Analysis of efficacy:
The trial will be analyzed according to the intention-to-treat principle. The effect of treatment with Ziprasidone will be assessed by analyzing changes in the score of the scale described above. Changes calculated from the evaluations before and after treatment will be analyzed by means of analysis of covariance, considering the baseline measurement as a covariate. The difference between treatment groups will be estimated with a 95% confidence interval and will be tested within this model by the corresponding two-sided test at the 5% level of significance.
Analysis of safety:
Safety analyses will be performed for patients who received at least one dose of the investigational drug. Rates of adverse events and of serious adverse events will be calculated with corresponding 95% confidence intervals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Ziprasidone HydrochlorideZiprasidone Hydrochloride oral solution with individual titration from 5 mg to 40 mg per day |
| 2 | Placebo comparator | Drug: PlaceboPlacebo oral solution |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- The subject and the authorized legal representative must understand the nature of the study and be able to comply with protocol requirements. The representative must sign an Informed Consent Document and the subject must provide Written Assent.
- The subject (male or female) must be between 7-17 (inclusive) years of age at screening.
- The subject must have a primary diagnosis of Conduct Disorder [CD] (312.8), Oppositional Defiant Disorder [ODD] (313.81) or Disruptive Behavior Disorder not otherwise specified [DBD-NOS] (312.9) as defined by DSM-IV criteria and confirmed by the Kiddie-SADS-PL.
- At the screening visit (Visit 1), subjects must have a score of 21 or more on the sum of the scales for conduct problems and for oppositional behaviour in the NCBRF-TIQ.
- In the investigator's opinion, the subject must be likely to benefit from the therapy.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Ziprasidone HydrochlorideAlso: Zeldox 10mg/ml Suspension zum EinnehmenZiprasidone Hydrochloride oral solution, individual titration 5 mg o.d. or 10 mg to 40 mg b.i.d | Drug | 1 |
| PlaceboAlso: Placebo Suspension zum EinnehmenPlacebo as oral solution, individually titrated | Drug | 2 |
Primary outcome
Nisonger Child Behavior Rating Form for typical IQ (NCBRF-TIQ): Combined subscales "Conduct Problem" and "Oppositional Behavior"
Time frame: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
5 secondary outcomes
Assessment of the safety and tolerability by adverse event documentation.
Time frame: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Assessment of the efficacy by the Clinical Global Impressions-Severity of Illness scale (CGI-S) and the Global Impressions-Improvement scale (CGI-I).
Time frame: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Correlation between dosage, efficacy and adverse events.
Time frame: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)
Ziprasidone serum levels
Time frame: Visit 5 (week 3) and Visit 8 (week 8)
Correlation between serum level, efficacy and adverse events
Time frame: Visit 5 (week 3) and Visit 8 (week 8)
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 18 Nov 2008.
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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.
Eberhard Schulz, MD principal investigator
University Hospital Freiburg, Dep. for Child & Adolescent Psychiatry
Christian Fleischhaker, MD study chair
University-Hospital Freiburg, Dep. for Child & Adolescent Psychiatry
Klaus Hennighausen, MD study director
University Hospital Freiburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ziprasidone Hydrochloride in people with Conduct Disorder and Oppositional Defiant 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 15 inclusion and 0 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 18 Nov 2008. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Nisonger Child Behavior Rating Form for typical IQ (NCBRF-TIQ): Combined subscales "Conduct Problem" and "Oppositional Behavior" (time frame: Visit 2 to Visit 9 (week 0, 1, 2, 3, 5, 7, 9 and 11)). 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 18 Nov 2008.