Drug therapy for Parkinson’s disease: An update

Table 2 Results of randomized, double-blind, placebo-controlled trials involving new antiparkinsonian drugs

Drug	Study objective	Outcomes	Adverse events	Ref.
Istradefylline	Evaluated the efficacy and safety of istradefylline, 20 and 40 mg once daily as adjunctive to L-dopa in patients with motor complications (12 wk)	↓ daily change in "off" time vs placebo	↑ dyskinesia	[203]
Istradefylline	Evaluated the efficacy and safety of istradefylline, 10, 20 and 40 mg once daily as adjunctive to L-dopa in patients with motor complications (12 wk)	No effect on "off" time duration Improved motor scores at 40 mg	-	[199]
Istradefylline	Evaluated the efficacy of istradefylline at an oral dose of 20 and 40 mg once daily for 12 wk in PD patients with motor complications on levodopa therapy	↓ "off" time vs placebo	↑ dyskinesia	[204]
Istradefylline	Evaluated the safety and efficacy of istradefylline 40 mg, as monotherapy in patients with PD	No significant effect in improving motor symptoms	-	[198]
Istradefylline	To evaluate efficacy, safety, and tolerability of istradefylline 20 mg once daily vs placebo as an adjunct to levodopa in PD subjects with motor fluctuations	↓ "off" time	Dyskinesia, lightheadedness, tremor, constipation, and weight decrease	[201]
Istradefylline	To evaluate safety and efficacy of istradefylline 20 or 60 mg/d in L-dopa-treated PD subjects with motor complications	↓ "off" time without an increase in “on” time	Dyskinesia, nausea, dizziness, and hallucinations	[200]
Istradefylline	To evaluate safety and efficacy of istradefylline 40 mg/d in L-dopa-treated PD subjects with prominent wearing-off motor fluctuations	↓ "off" time without increased troublesome dyskinesia	-	[202]
Istradefylline	To evaluate safety and efficacy of istradefylline 20 or 40 mg/d in patients with L-dopa-motor fluctuations and peak-dose dyskinesias	↓ "off" time	Severity of dyskinesia was unchanged, but "on" time with dyskinesia increased	[205]
Preladenant	To evaluate efficacy of using preladenant 5 mg twice a day as a levodopa adjunct in subjects with fluctuating PD	↓ "off" time ↑ "on" time throughout the 36-wk treatment relative to the baseline	Dyskinesia and constipation	[209]
Preladenant	To evaluate safety of single and multiple rising preladenant doses compared with placebo	Preladenant was generally well tolerated up to the maximum dose tested (200 mg/d)	Transient mild increases in blood pressure within a few hours after preladenant administration	[207]
Preladenant	To evaluate efficacy and safety of 1, 2, 5, or 10 mg oral preladenant twice daily in patients with PD and motor fluctuations on L-dopa	5 and 10 mg preladenant ↓ "off" time	Worsening of PD, dyskinesia, nausea, constipation, and insomnia	[208]
Safinamide	To evaluate efficacy and safety of safinamide 50 or 100 mg/d, as add-on to L-dopa in the treatment of PD patients with motor fluctuations	↑ total on time with no or nontroublesome dyskinesia, ↓ decreased off time, without worsening dyskinesia	-	[216]
Safinamide	To evaluate efficacy of safinamide 100 or 200 mg/d as add-on treatment to single dopaminergic receptor agonist single in early PD	Safinamide 100 mg/d may be effective as add-on treatment	-	[215]
Safinamide	To evaluate efficacy and safety of once-daily 100 or 200 mg safinamide in patients with early PD receiving a stable dose of a single dopaminergic receptor agonist	Safinamide 100 mg/d improved motor symptoms (UPDRS part III total score)	-	[214]
Zonisamide	To evaluate the efficacy, safety and tolerability of daily doses of 25, 50, and 100 mg of zonisamide as an adjunctive treatment in PD	Zonisamide 25 and 50 mg/d improved motor symptoms (UPDRS part III total score) Zonisamide 50 and 100 mg ↓ "off" time without ↑ dyskinesia	-	[221]
Isradipine	To establish a tolerable and efficacious dosage of isradipine controlled-release in subjects with early PD not requiring dopaminergic therapy	The tolerability of 5, 10, or 20 mg of isradipine was dose dependent No difference in change in UPDRS among dosages	Peripheral oedema and dizziness	[295]
Isradipine	To evaluate safety and tolerability of isradipine controlled release in patients with early PD	Tolerability of isradipine CR 5, 10, 15, or 20 mg was dose dependent Isradipine had no significant effect on blood pressure or PD motor disability	Leg oedema and dizziness	[294]

L-dopa: Levodopa; PD: Parkinson’s disease; UPDRS: Unified Parkinson’s disease rating scale; CR: Controlled release.