Table 1.
Efficacy and safety of the newly approved drugs for treatment of PD.
| Drug Name | Author, Year, Reference Number | Study Design | Population Characteristics | Interventions | Primary Outcome Measured | Efficacy | Safety |
|---|---|---|---|---|---|---|---|
| Safinamide | Schapira A., et al., 2013 [88] |
Randomized, placebo-controlled, double-blind international Phase III trial. | Patients who had mid-to-late-stage idiopathic PD (>3 years of disease) and were treated with optimized, stable doses of L-dopa and DA, catechol-O-methyltransferase inhibitor, anticholinergic, and/or amantadine. | Safinamide 50 mg, Safinamide 100 mg, placebo. | Change in daily on time with no or non-troublesome dyskinesia. | Improved on time (without worsening the troublesome dyskinesia), off time, UPDRS part III, CGI-S, CGI-C, PDQ-39 and off time following the first morning L-dopa dose. | Major AEs: Back pain, headache, falls, dyskinesias, nausea, and urinary tract infections |
| Borgohain R., et al., 2014 [90] |
Randomized, placebo-controlled, double-blind Phase III trial. (Study 016) |
Patients aged 30–80 years, had been diagnosed with PD ≥3 years, had the presence of motor fluctuations with 1.5 h off a day. | Safinamide 50 mg, Safinamide 100 mg, placebo. | Change in mean daily on time with no or non-troublesome dyskinesias in the 18-h recording period. | Improved UPDRS part III in both safinamide 50 mg (p = 0.0138) and 100 mg (p = 0.0006) groups. Significant improvement in off time, CGI-C and CGI-S in both safinamide groups following the morning dose of levodopa. |
Major AEs: Back pain, headache, dyskinesia, depression, and hypertension |
|
| Borgohain R., et al., 2014 [91] |
Randomized, double-blind, placebo-controlled, 18-month extension study. (Study 018) |
Patients who had completed the 016 study or patients who had completed efficacy evaluation at weeks 12 and 24 of Study 016. | Safinamide 50 mg, Safinamide 100 mg, placebo. | Mean change from baseline at Study 016 to endpoint of the DRS score during on time. | Improved total daily on time without troublesome dyskinesia from baseline for safinamide 50 mg (p = 0.0031) and safinamide 100 mg (p = 0.0002). Improved off time, CGI-S, CGI-C (for SAF 50 mg), UPDRS part II, part III and part IV total scores and PDQ-39. | Major AEs: Back pain, insomnia, headache, and dyskinesia |
|
| Stocchi F., et al., 2004 [93] |
Randomized, placebo-controlled, double-blind, Phase II, dose finding study. | Early PD patients. | Safinamide 0.5 mg/kg, Safinamide 1.0 mg/kg, placebo as monotherapy or as adjunct therapy to a single DA. | Proportion of patients considered as treatment responders, for example 30% improvement in UPDRS part III compared with baseline. | Improved UPDRS part III as compared to baseline, more statistically significant between safinamide 1.0 mg/kg and placebo (p = 0.016). | Major AEs: Abdominal pain, dizziness, and musculoskeletal and connective tissue disorders |
|
| Stocchi F., et al., 2006 [94] | Single-center, open, pilot trial. | 25 PD patients with Hoehn and Yahr (H&Y) stages III–IV. | Safinamide 100 mg, Safinamide 150 mg, Safinamide 200 mg as adjunct therapy to stable single DA or LD. | Changes in UPDRS part II, part III, and part IV and CGI. | Improved motor performance (evaluated by UPDRS part III) for more than an 8-week period (p < 0.001). | Major AEs: - |
|
| Stocchi F., et al., 2012 [95] |
Randomized, placebo-controlled, double-blind Phase III trial. (Study 015) |
Early PD patients aged 30–80 years, who were diagnosed with idiopathic PD with <5 years of history and had Hoehn and Yahr (H&Y) stages I–II. | Safinamide 100 mg, Safinamide 200 mg, placebo as adjunct therapy to stable single DA. | Changes in UPDRS part III total score from baseline to endpoint (week 24). | Improved UPDRS part II, UPDRS part III and CGI-C total score in safinamide 100 mg group (p = 0.0419). | Major AEs: Nausea, vomiting, headache, dizziness, back pain, gastritis, and abdominal pain |
|
| Schapira A., et al., 2013. [96] |
Randomized, double-blind, placebo-controlled, 12-month extension study. (Study 017) | Patients who had completed Study 015 or patients who had completed efficacy evaluation at weeks 12 and 24 of Study 015. | Safinamide 100 mg, Safinamide 200 mg, placebo as adjunct therapy to stable single DA. | Time to intervention from baseline. | Lower rate of intervention in the safinamide 100 mg group compared with dopamine agonists monotherapy (p < 0.05). Improved UPDRS part II and part III was greater in safinamide 100 mg group. | Major AEs: Dizziness, nausea, back pain, nausea, and upper abdominal pain |
|
| Barone P., et al., 2013 [97] |
Randomized, placebo-controlled, double-blind international Phase III trial. | Patients with early idiopathic PD (<5 years) who were treated with a single DA. | Safinamide 50 mg, Safinamide 100 mg, placebo. | Change in UPDRS part III from baseline to week 24. | Improved UPDRS part III (p = 0.0396) and PDQ-39 in the safinamide 100 mg group. | Major AEs: Nausea, dizziness, headache, arthralgia, and back pain |
|
| Istradefylline | Mizuno Y., et al., 2013 [57] | Multicenter, placebo-controlled, randomized, double-blind, parallel-group study. | PD patients with motor complication. | Istradefylline 20 or 40 mg/day and placebo. | Change in daily off time. | The change in daily off time was significantly reduced in the istradefylline 20 mg/day (−0.99 h, p = 0.003) and istradefylline 40 mg/day (−0.96 h, p = 0.003) groups. | Major AEs: Dyskinesia, gait disturbance, gastric ulcer, and hallucinations |
| Pimavanserin | Espay A., et al., 2018 [99] | 6-week randomized, double-blind, placebo-controlled, phase 3 trial. | Patients with PD psychosis. | Pimavanserin 34 mg and placebo. | Change in the Scale for the Assessment of Positive Symptoms-PD. | Mean (pimavanserin vs. placebo) change from baseline was larger in the cognitively impaired (n = 50; −6.62 vs. −0.91; p = 0.002) versus the cognitively unimpaired (n = 135; −5.50 vs. −3.23; p = 0.046) group. The mean difference in SAPS-PD score change from baseline for pimavanserin versus placebo was −3.06 at day 43 (p = 0.001). | Major AEs: Urinary tract infection, fall, peripheral edema, hallucinations, nausea, and confusional state |
| Cummings J., et al., 2018 [109] | 6-week, randomized, double-blind, placebo-controlled study. | Patients with PD psychosis. | Pimavanserin 40 mg and placebo. | SAPS-PD score change from baseline to week 6. | Pimavanserin was associated with statistically significant 5.79 point improvement at week 6 as compared to placebo with 2.73 point (p = 0.001) | Major AEs: Nausea, headache, fall, urinary tract infection, peripheral edema, confusional state, and hallucinations |