Adjuvant therapies for Parkinson’s disease: critical evaluation of safinamide

Figures & data

Table 1 Clinical trials performed in PD population

Trial	Authors	Study design	Type of intervention	Population	Primary outcomes
A Phase II, dose-finding study to investigate the efficacy and safety of SAF in patients with early PD (NW-1015/009/II/2001)	Stocchi et al^Citation10	Randomized, double-blind, placebo-controlled, dose-finding study	Monotherapy or adjunct therapy to stable single DA	172 early PD patients (56 per group of treatment)	Proportion of patients considered as treatment responders, ie, ≥30% improvement in UPDRS part III compared with baseline
An open-label, dose-titration study to investigate the safety and clinical tolerability of SAF as add-on therapy followed by 24-month follow-up period (NW-1015/012/II/2003)	Stocchi et al^Citation11	Pilot, open-label, single-center study	Adjunct therapy to stable single DA or LD	25 PD patients with H&Y III–IV: Group 1: eleven with motor fluctuations and stable LD dosage Group 2: 14 with single DA	Changes in UPDRS part II, part III, and part IV and CGI
A Phase III trial to determine the efficacy and safety of low-dose (50–100 mg/d) and high-dose (150–200 mg/d) range of SAF in early PD patients (NW-1015/015/III/2003)	Stocchi et al^Citation12	Randomized, double-blind, placebo-controlled trial	Adjunct therapy to stable single DA	269 early PD patients. Randomization 1:1:1 (low-dose, high-dose and placebo); 90 patients per group	Changes in UPDRS part III total score from baseline to endpoint (week 24)
A Phase III, 12-month extension study to investigate the efficacy and safety of dose range of SAF (50–200 mg/d) in early PD patients (NW-1015/017/III/2003)	Schapira et al^Citation16	Double-blind, placebo-controlled trial	Adjunct therapy to stable single DA	227 early PD patients participating in the 015 study^Citation12	Time from baseline (randomization in 015 study) to intervention defined as an increase in the dose of DA; addition of another DA, LD, or other PD treatment; or discontinuation due to the lack of efficacy
A Phase III trial to determine the efficacy and safety of low (50 mg/day) and high (100 mg/d) doses of SAF in PD patients with motor fluctuations (NW-1015/016/III/2006)	Borgohain et al^Citation19	Randomized, double-blind, placebo-controlled, parallel group trial	Adjunct therapy to stable LD dosage plus stable DA and/or anticholinergic	669 fluctuating PD patients	Change from baseline to endpoint in daily on time (on time without dyskinesias and on time with minor dyskinesias) in the 18-hour recording period
A Phase III, double-blind, placebo-controlled, 18-month extension study of long-term efficacy and safety of 50 mg/d and 100 mg/d doses of safinamide, as add-on therapy, in idiopathic PD patients with motor fluctuations, treated with levodopa, who may be receiving DA and/or anticholinergic	Borgohain et al^Citation20	Randomized, double-blind, placebo-controlled, parallel group extension study to Study 016^Citation19	Adjunct therapy to LD	544 PD patients who had completed the 016 study or completed efficacy evaluation at Weeks 12 and 24 during the 016 study	Mean change from baseline at Study 016 to endpoint of the total score of the dyskinesia rating scale during on time

Abbreviations: PD, Parkinson’s disease; SAF, safinamide; DA, dopamine agonist; UPDRS, Unified Parkinson’s Disease Rating Scale; LD, levodopa; CGI, clinical global impression; H&Y, Hoehn and Yahr.

Figure 1 Percentage of patients showing decreasing, no change, and increasing DRS scores (analysis for population with DRS ≥0 and no change in the l-dopa dosage during the 24-month study).

Note: Adapted from Cattaneo et al.²¹
Abbreviations: DRS, Dyskinesia Rating Scale; l-dopa, levodopa; SAF, safinamide.

Table 2 Study 015: TEAEs reported by at least 5% of patients in any treatment groups

	Placebo (n=90)	Safinamide 50–100 mg (n=90)	Safinamide 150–200 mg (n=89)
At least one AE	47 (52.2)	57 (63.3)	47 (52.8)
Nausea	6 (6.7)	7 (7.8)	8 (9.0)
Cough	4 (4.4)	6 (6.7)	5 (5.6)
Pyrexia	6 (6.7)	5 (5.6)	5 (5.6)
Gastritis	2 (2.2)	4 (4.4)	5 (5.6)
Nasopharyngitis	1 (1.1)	4 (4.4)	5 (5.6)
Hypertension	3 (3.3)	0 (0.0)	5 (5.6)
Dizziness	2 (2.2)	5 (5.6)	4 (4.5)
Abdominal pain	4 (4.4)	6 (6.7)	1 (1.1)
Peripheral edema	4 (4.4)	5 (5.6)	3 (3.4)
Back pain	3 (3.3)	5 (5.6)	3 (3.4)
Headache	8 (8.9)	4 (4.4)	4 (4.5)
Tremor	1 (1.1)	5 (5.6)	3 (3.4)
Vomiting	6 (6.7)	5 (5.6)	2 (2.2)
Blurred vision	4 (4.4)	5 (5.6)	2 (2.2)

Note: Total safety population (N=269).

Abbreviations: TEAE, treatment emergent adverse event; AE, adverse event.

Table 3 Study 016: most common AE reported by at least 5% of patients in any treatment groups

	Placebo (n=222)	Safinamide 100 mg (n=224)	Safinamide 50 mg (n=223)
Dyskinesia	28 (12.6)	41 (18.3)	47 (21.1)
Worsening PD	18 (8.1)	9 (4.0)	12 (5.4)
Cataract	13 (5.9)	14 (6.3)	11 (4.9)
Back pain	13 (5.9)	12 (5.4)	10 (4.5)
Depression	12 (5.4)	4 (1.8)	2 (0.9)
Headache	10 (4.5)	11 (4.9)	13 (5.8)
Hypertension	8 (3.6)	10 (4.5)	13 (5.8)

Abbreviations: AE, adverse event; PD, Parkinson’s disease.

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