Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders
Condition: Conduct Disorder; Oppositional Defiant Disorder
MeSH terms: Mental Disorders; Problem Behavior; Conduct Disorder; Attention Deficit and Disruptive Behavior Disorders
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Ziprasidone Hydrochloride; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ziprasidone Hydrochloride oral solution, individual titration 5 mg o.d. or 10 mg to 40 mg b.i.d; Placebo as oral solution, individually titrated
Other intervention name(s): Zeldox 10mg/ml Suspension zum Einnehmen; Placebo Suspension zum Einnehmen
Intervention MeSH terms: Ziprasidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment