The P-I-E-N-O Parkinsn's List Drug Database

Mail converted by MHonArc 2.6.10

PIENO Google Custom Search

Site Hosting donated by & Grant from The Parkinson Alliance

ropinerole / Requip^TM Insert Page 3

Statistically significant differences between the percentage of responders on Requip^TM compared to placebo were seen after 8 weeks of treatment.

In addition, the mean percentage improvement from baseline in the Total Motor Score was 43% in Requip^TM treated patients compared with 21% in placebo treated patients (p=0.018).

Statistically significant differences in UPDRS motor score between Requip^TM and placebo were seen after 2 weeks of treatment. The median daily dose at which a 30% reduction in UPDRS motor score was sustained was 4 mg. The second trial in early Parkinson's disease (without L-dopa) patients was a double-blind, randomized, placebo-controlled 6-month study. Patients were essentially similar to those in the study described above; concomitant use of selegiline was allowed, but patients were not permitted to use anticholinergics or amantadine during the study. Paitents had a mean disease duration of 2 years and limited (not more that a 6-week period) or no prior exposure to L-dopa. The starting dose of Requip^TM in this trial was 0.25 mg t.i.d. The dose was titrated at weekly intervals by increments of 0.25 mg t.i.d. to a dose of 3.0 mg t.i.d. and then weekly at increments of 1.0 mg t.i.d. Patients were to be titrated to a dose of at least 1.5 mg t.i.d. and then to their maximally tolerated dose, up to a maximum of 8.0 mg t.i.d. The mean dose attained in patients at study endpoint was 15.7 mg/day.

The primary measure of effectiveness was the mean percent reduction (improvement) from baseline in the UPDRS Motor Score. In this study 241 patients were enrolled. At the end of the 6-month study, Requip^TM treated patients had 22% improvement in motor score, compared with a 4% worsening in the placebo group (p<0.001).

Statistically significant differences in UPDRS motor score improvement between Requip^TM and placebo were seen after 12 weeks of treatment.

Study in Patients with Advanced Parkinson's Disease (with L-dopa)

This double-blind, randomized, placebo-controlled 6-month trial evaluated 148 patients (Hoehn & Yahr II-IV) who were not adequately controlled on L-dopa. Patients in this study had a mean disease duration of approximately 9 years, had been exposed to L-dopa for approximately 7 years, and had experienced "on-off" periods with L-dopa therapy. Patients previously receiving stable doses of selegiline, amantadine and/or anticholinergic agents could continue on these agents during the study. Patients were started at a Requip^TM dose of 0.25 mg t.i.d. and titrated upward by weekly intervals until an optimal therapeutic response was achieved. The maximum dose of study medication was 8 mg t.i.d. All patients had to be titrated to at least a dose of 2.5 mg t.i.d. Patients could then be maintained on this dose level or higher for the remaineder of the study. Once a dose of 2.5 mg t.i.d. was achieved, patients underwent a mandatory reduction in their L-dopa dose, to be followed by additional mandatory reductions with continued escalation of the Requip^TM dose. Reductions in the dosage of L-dopa were also allowed if patients experienced adverse events that the investigator considered related to dopaminergic therapy. The mean dose attained at study endpoint was 16.3 mg/day. The primary outcome was the proportion of responders, defined as patients who were able both to achieve a decrease (compared to baseline) of a least 20% in their L-dopa dose and a decrease of at least 20% in the proportion of the time awake in the "off" condition (a period of time during the day when patients are particularly immobile), as determined by patient diary. In addition, the mean percent change from baseline in daily L-dopa dose was examined.

At the end of 6 months, 28% of Requip-treated patients were classified as responders (based on combined endpoint) while 11% of placebo-treated patients were responders (p=0.02). Based on the protocol-mandated reductions in L-dopa dosage with escalating Requip^TM doses, Requip-treated patients had a 19.4% mean reduction in L-dopa dose while placebo treated patients had a 3% reduction (p<0.001)L-dopa dosage reduction was also allowed during the study if dyskinesias or other dopaminergic effects occurred. Overall, reduction of L-dopa dose was sustained in 87% of Requip-treated patients and in 57% of patients on placebo. On average, the L-dopa dose was reduced by 31% in Requip-treated patients.

The mean number of "off" hours per day during baseline was 6.4 hours for Requip-treated patients and 7.3 hours for patients treated with placebo. At the end of the 6-month study, patients treated with Requip^TM had a mean of 4.9 hours per day of "off" time, while placebo-treated patients had a mean of 6.4 hours per day of "off time.

INDICATIONS AND USAGE

Requip^TM (ropinirole hydrochloride) is indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.

The effectiveness of Requip^TM was demonstrated in randomized, controlled trials in patients with early Parkinson's disease who were not receiving concomitant L-dopa therapy as well as in patients with advanced disease on concomitant L-dopa (see CLINICAL PHARMACOLOGY, Clinical Trials).

CONTRAINDICATIONS

Requip^TM is contraindicated for patients known to have hypersensitivity to the product.

WARNING

Syncope

Syncope, sometimes associated with bardycardia, was observed in association with ropinirole in both early Parkinson's disease (without L-dopa) patients and advanced Parkinson's disease (with L-dopa) patients. In the two double-blind placebo-controlled studies of Requip^TM in patients with Parkinson's disease who were not being treated with L-dopa, 11.5% (18 of 157) of patients on Requip^TM had syncope compared to 1.4% (2 of 147) of patients on placebo. Most of these cases occurred more than 4 weeks after initiation of therapy with Requip, and were usually associated with a recent increase in dose.

Of 208 patients being treated with both L-dopa and Requip^TM in placebo-controlled advanced Parkinson's disease trials, there were reports of syncope in 6 (2.9%) compared to 2 of 120 (1.7%) of placebo/L-dopa patients.

Because the studies of Requip^TM excluded patients with significant cardiovascular disease, it is not known to what extent the estimated incidence figures apply to Parkinson's disease patients as a whole.

Two of 47 Parkinson's disease patient volunteers enrolled in phase 1 studies had syncope following a 1 mg dose. In phase 1 studies including 110 healthy volunteers, one patient developed hypotension, bradycardia, and sinus arrest of 26 second accompanied by syncope, the patient recovered spontaneously without intervention. One other healthy volunteer reported syncope.

Next Page of ropinerole/Requip^TM Insert

Parkinsn's Archive Treasures Page

John Cottingham is the webmaster of this site.