Open Label, Multicentre Extension Study of Protocol 42603ATT3002 to Evaluate Safety of Prolonged Release OROS Methlyphenidate in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
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.
|Attention Deficit Disorder With Hyperactivity||Drug: double blind placebo Drug: double blind PR OROS methylphenidate Drug: open label PR OROS methylphenidate||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||An Open International Multicentre Long-Term Follow Up Study to Evaluate Safety of Prolonged Release OROS Methlyphenidate in Adults With Attention Deficit Hyperactivity Disorder|
- Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Treatment duration for OL extended from 52 wks to 72 wks (International Amendment 2) or 108 wks in Germany. Treatment duration for double-blind (DB) randomized withdrawal: 4 weeks ]To evaluate the long term safety and tolerability of PR OROS MPH (18, 36, 54, 72 and 90 mg/day) in adults with Attention Deficit Hyperactivity Disorder (ADHD)
- Change From DB Baseline in Conners' Adult ADHD Rating Scale (CAARS) Total Score at DB Endpoint [ Time Frame: DB baseline, DB endpoint ]
To evaluate maintenance of treatment effects of PR OROS MPH vs. placebo as measured on CAARS.
CAARS assesses ADHD symptoms and behaviors in adults. best value: 0 worst value: 54
Endpoint: last available post-baseline assessment.
- Change From OL Baseline to OL Endpoint in Conners' Adult ADHD Rating Scale (CAARS) Total and Subscale Scores [ Time Frame: OL baseline, OL endpoint ]
Long term efficacy of PR OROS MPH as assessed by investigator-rated CAARS total score, hyperactivity/impulsivity subscale score and inattention subscale score.
Subscale scores: best value: 0, worst value: 27
- Change From OL Baseline in Clinical Global Impression Scale (CGI-S) Score at OL Endpoint [ Time Frame: OL baseline, OL endpoint ]Assessment of the long term effect on overall functioning measured by CGI-S best score: 1 worst score: 7
- Change From OL Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Score at OL Endpoint [ Time Frame: OL baseline, OL endpoint ]Quality of life measured by Q-LES-Q best score: 100 worst score: 0
- Change From DB Baseline to DB Endpoint in CGI-S Score [ Time Frame: DB baseline, DB endpoint ]evaluation of treatment effects as rated by the investigator on the CGI-S scale. CGI-S is used to rate the severity of a subject's illness on a 7- point scale ranging from 1 (not ill) to 7 (extremely severe).
- Change From DB Baseline to DB Endpoint in CAARS Self Rated Scale (CAARS-S:S) Total Score [ Time Frame: DB baseline, DB endpoint ]Evaluation of treatment effects as rated by the subjects on the CAARS-S:S. best score: 0 worst score: 104
|Study Start Date:||January 2006|
|Study Completion Date:||July 2008|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
open label PR OROS methylphenidate Flexible dosage MPH (18 to 90 mg/day) for 72 weeks (108 weeks for Germany)
Drug: open label PR OROS methylphenidate
Flexible dosage MPH (18 to 90 mg/day) for 72 weeks (108 weeks for Germany)
double blind PR OROS methylphenidate 18 36 54 72 or 90 mg/day once daily for 4 weeks
Drug: double blind PR OROS methylphenidate
18, 36, 54,72 or 90 mg/day once daily for 4 weeks
Placebo Comparator: 003
double blind placebo matching placebo tablets once daily for 4 weeks
Drug: double blind placebo
matching placebo tablets once daily for 4 weeks
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00307684
|Freiburg I. Br., Germany|
|Porto N/A, Portugal|
|Basel Bs, Switzerland|
|Study Director:||Janssen-Cilag International NV Clinical Trial||Janssen-Cilag International NV|