Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders

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Brief Title

Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders

Official Title

Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders in Children and Adolescents - a Placebo Controlled, Randomized, Double Blind Clinical Trial

Brief 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.

      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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Nisonger Child Behavior Rating Form for typical IQ (NCBRF-TIQ): Combined subscales "Conduct Problem" and "Oppositional Behavior"

Secondary Outcome

 Assessment of the safety and tolerability by adverse event documentation.

Condition

Conduct Disorder

Intervention

Ziprasidone Hydrochloride

Study Arms / Comparison Groups

 1
Description:  Ziprasidone Hydrochloride oral solution with individual titration from 5 mg to 40 mg per day

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

51

Start Date

July 2006

Completion Date

June 2008

Primary Completion Date

June 2008

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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.
      

Gender

All

Ages

7 Years - 17 Years

Accepts Healthy Volunteers

No

Contacts

Eberhard Schulz, MD, , 

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT00676429

Organization ID

NRA1280023

Secondary IDs

EudraCT: 2006-002207-13


Study Sponsor

University Hospital Freiburg

Collaborators

 Pfizer

Study Sponsor

Eberhard Schulz, MD, Principal Investigator, University Hospital Freiburg, Dep. for Child & Adolescent Psychiatry


Verification Date

November 2008