Open Label, Multicentre Extension Study of Protocol 42603ATT3002 to Evaluate Safety of Prolonged Release OROS Methlyphenidate in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Condition: Attention Deficit Disorder With Hyperactivity
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 3

Summary: 
      Trial 42603ATT3004 is an open-label extension study to clinical trial 42603ATT3002
      (NCT00246220). In trial 42603ATT3002 the efficacy and safety of OROS methylphenidate was
      assessed in adult subjects with Attention Deficit Hyperactivity Disease (ADHD). ADHD is a
      developmental disorder beginning in childhood and characterized by developmentally
      inappropriate inattention, hyperactivity and impulsiveness. Data on the number of adult
      patients with ADHD is limited, but it is estimated that approximately 50% of children with
      ADHD will have symptoms also in adhulthood. The drug tested in this trial is OROS
      methylphenidate. The active ingredient is methylphenidate and the tablet is designed to
      release the active ingredient gradually to ensure an effect, which lasts up to 12 hours.
      Trial 42603ATT3002 consisted of a 5-week period, where subjects were assigned to either
      receive placebo (empty drug) or one out of three different dosages of OROS methylphenidate.
      This 5-week period was followed by a 7-week period, where patients received OROS
      methylphenidate at their optimal dose. In study 42603ATT3004, subjects who complete
      42603ATT3002 are followed for a period of at least 52 weeks to evaluate safety and
      tolerability of OROS methylphenidate in patients who are treated with OROS methylphenidate
      over a long period of time.

      Amendment: At the end of the open-label period of the present study 42603ATT3004, patients
      are enrolled into a double-blind placebo-controlled period, which lasts an additional 4
      weeks. The purpose of this double-blind placebo-controlled period is to evaluate the
      maintenance of effect under continued treatment with OROS methlyphenidate in comparison to
      treatment cessation in those patients, who are randomized into the placebo-group.
    

Detailed description: 
      This is an open label, multicentre extension study to trial 42603ATT3002. Patients, who were
      enrolled to trial 42603ATT3002 must have had a diagnosis of ADHD with some symptoms already
      present at the age of 7 and continuing in adulthood. The patients must have had at least mild
      to moderate symptoms of ADHD. In trial 42603ATT3002 the efficacy and safety of three fixed
      dosages of the study drug OROS methlyphenidate (MPH) was compared with placebo in adult
      subjects with ADHD in a double-blind phase. This double-blind phase was followed by an
      open-label phase, which was designed to assess the safety and tolerabiltiy of the study drug
      OROS methylphenidate in these subjects, when they got a dose, which was optimal to control
      their symptoms. In trial 42603ATT3004 patients are enrolled who completed the open-label
      phase of trial 42603ATT3002. Trial 42603ATT3004 is designed to assess the long-term safety
      and tolerabilty of OROS methylphenidate over a period of 52 weeks at a dose, which is optimal
      to control the symptoms. Patients may enter the extension study 42603ATT3004 at Visit 8
      (End-of-Phase Visit, Open Label) of the 42603ATT3002 study as long as the patient has given
      informed consent prior to the visit being performed. Visit 8 data may then serve as baseline
      data for the extension study. These patients should continue treatment at the same optimal
      dosage of PR OROS methylphenidate as was attained during the open label phase of protocol
      42603ATT3002. Patients who complete the 42603ATT3002 study, including post-study visit, may
      enter the extensions study up to 30 calendar days from the last dosing of open label trial
      medication of the 42603ATT3002 study. Patients should be titrated accordingly to their
      optimal dose attained in study 42603ATT3002. Patients will be assessed at regular intervals
      for at least 52 weeks.

      Amendment: At completion of the open-label phase, patients can participate in a double-blind
      placebo-controlled phase, provided that they are giving written informed consent. At
      inclusion to the double-blind placebo-controlled phase, patients are assigned to one of two
      treatment arms by chance. One treatment arm will continue taking the same treatment at the
      same daily dose as during the open-label period. The other treatment arm will receive placebo
      treatment. As placebo, an inactive formulation or an empty treatment will be used. During the
      double-blind placebo-controlled phase, patients are asked to return to their doctor's office
      every other week. During these visits, physical examinations will be made, efficacy measures
      will be taken by means of questionnaires, that need to be completed either by the treating
      physician or the patient and any unwanted side effect will be recorded and treated if needed.
      One week after the end of the double-blind, placebo-controlled phase, patients have to return
      one more time to their doctor's office for the so called post-study visit, during which an
      additional physical examination will be performed and additional safety and efficacy
      parameters will be assessed.Patients will be assessed at regular intervals for at least 52
      weeks. Daily oral dosages of 18, 36, 54, 72 and 90mg will be available and may be increased
      or decreased by 18mg increments based on clinical observations of response and tolerability
      for at least 52 weeks. Amendment: During the double-blind, placebo-controlled phase, patients
      will receive either active treatment at the previously assessed optimal dose or placebo
      tablets for a total of 4 weeks. Both treatments (active or placebo) are taken by mouth once
      per day in the morning.
    

Intervention name(s): double blind placebo; double blind PR OROS methylphenidate; open label PR OROS methylphenidate
Intervention type(s): Drug; Drug; Drug
Intervention description(s): matching placebo tablets once daily for 4 weeks; 18, 36, 54,72 or 90 mg/day once daily for 4 weeks; Flexible dosage MPH (18 to 90 mg/day) for 72 weeks (108 weeks for Germany)
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Attention Deficit Hyperactivity Disorder; Adult; Long term safety; Efficacy; Quality of life