Table 2.
Summary of double-blind studies assessing the efficacy of intermittent subcutaneous injections of apomorphine in patients with Parkinson’s disease
| Study | Pts (N) | Study duration | Study design | Primary efficacy endpoint | Mean injection dose/mean total daily dose, mg | Minutes to clinical onset | Duration of effect, minutes | Efficacy findings |
|---|---|---|---|---|---|---|---|---|
| Van Laar et al. [106] | 5 | 10 doses | Randomized, double-blind, placebo-controlled, crossover study | Columbia Parkinson’s Disease score | 2.7/NR | 7.3 | 96 | Significant efficacy of apomorphine in improving all scores of the Columbia scale |
| Ostergaard et al. [107] | 22 | 2 months | Double-blind, placebo-controlled study | “Off” time reduction | 3.4/NR | NR | NR | Mean daily “off” duration reduced by 58%; “off” severity also significantly reduced |
| Merello et al. [49] | 12 | Single dose | Double-blind, active comparator (dispersible levodopa) | Change in modified Webster disability scale score | 3/3 | 8.1 | 56.6 | Mean effect latency and duration for apomorphine vs. levodopa: 8.08 |
| Dewey et al. (APO202) [50] | Phase 1: 29 | Single dose | Placebo-controlled, parallel-group inpatient evaluation | Change in UPDRS motor score | 5.4/NR | NR | NR | Significant motor improvement (respectively − 23.9 vs. − 0.1 change in UPDRS motor score) |
| Phase 2: 26 | 1 month | Placebo-controlled, parallel-group outpatient evaluation | “Off” time reduction | 5.8/14.5 | 22 | NR | Significant reduction of reported “off” time (respectively 2.0 vs. 0.0 h) | |
| Pfeiffer et al. (APO302) [108] | 62 | Single dose | Prospective, placebo-controlled, parallel-group study | Change in UPDRS motor score after 20 min | TED or TED plus 2.0 mg | 7.3 | NR | Significant improvement for pooled apomorphine vs. placebo (− 24.2 vs. − 7.4 mean reduction in UPDRS) |
| Pahwa et al. (APO301) [56] | 56 | Single dose | Dose-escalation study, randomized, placebo-controlled, crossover evaluation | Change in UPDRS motor score after 20 min | 4.0–10.0 | NR | NR | Significant improvement in UPDRS motor scores in apomorphine group vs. placebo at 20, 40, 90 min |
| Hattori et al. [109] | 31 |
3 months (open label) Single dose (blinded evaluation) |
Placebo-controlled blinded efficacy assessment following a 12-week unblinded outpatient phase | Change in UPDRS motor score after 20 and 40 min | 1.55/4.49 | 14.2 | 62.6 | Significant improvement in UPDRS motors scores with apomorphine vs. placebo at 20 and 40 min |
NR not reported, pts patients, TED typically effective dose, UPDRS Unified Parkinson’s Disease Rating Scale