| Participants |
154 patients, 10 withdrawals due to adverse effects. 3 from placebo group, 2 from 50 mg tid tolcapone group, 1 from 200 mg tid tolcapone group and 4 from 400 mg tid tolcapone group.
95 men. Mean age 63 years, mean disease duration 11 years, mean levodopa dose 734 mg/day.
Inclusion criteria: Patients aged 40 or more with clinically idiopathic PD, and presented the 'wearing‐off' phenomenon despite 'optimal' antiparkinsonian therapy, with 'off' time comprising more than 25% of the waking day, despite at least 5 doses of levodopa. Have used levodopa for at least 2 years and have reached or almost reached the threshold of tolerability as shown by mild‐to‐moderate dyskinesia or newly occurring dyskinesia after slight increase in levodopa dose. Patients must have been receiving a stable dose of a standard levodopa/decarboxylase inhibitor formulation, in a 4:1 ratio, for at least 2 months prior to enrolment, although a bedtime dose of slow‐release formulation was permitted. Disease severity of no more than 3 on H&Y scale. Women had to have been amenorrhoeic for at least 1 year or surgically sterile for at least 6 months. Patients were required to keep reliable 'on/off' charts.
Exclusion criteria: Non‐idiopathic parkinsonism, predominately trembling symptomatology, unpredictable motor fluctuations, or diphasic dyskinesia in response to levodopa. Patients treated with levodopa alone, levodopa/carbidopa 10:1 ratio, levodopa in a controlled release formulation during the day, a total daily dose of greater than 1200 mg levodopa, fewer than 5 or more than 8 daily intakes. Treatment with neuroleptics, antidepressants (except low‐dose tricyclic antidepressants at bedtime), selegiline, or any investigational drug within preceding 2 months, apomorphine in the preceding week, antiemetics, high protein binding drugs(>90%), or moderately high protein‐binding drugs with a narrow therapeutic range. Patients with unstable medical problems, significant organic disease or related treatments, a history of alcoholism or drug abuse, or evidence of previous myocardial infarction, arrhythmia, or conductance defects on electrocardiography. |
