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PRODUODOPA has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with advanced PD. 1
A Phase 3, single-arm, open-label study evaluating the safety, tolerability, and efficacy of 24-hour daily exposure with a continuous subcutaneous infusion of PRODUODOPA in patients with advanced PD (N=244) at 52 weeks. Of 244 enrolled patients, 107 (44%) discontinued treatment and 137 completed treatment with PRODUODOPA. 1
Safety and tolerability were the primary endpoints. The proportion of patients reporting adverse events, changes in laboratory parameters, vital sign measurements, and electrocardiogram values from baseline. Local skin tolerability was additionally assessed by the Infusion Site evaluation scale. 1
Secondary endpoints included change from baseline in the average daily normalised ‘Off’ time and ‘On’ time as assessed by the PD diary and normalised to a 16-hour waking day, MDS-UPDRS Parts I-IV (with Part III measured in the patient’s best on state), Parkinson’s Disease Sleep Scale-2 (PDSS-2), 39-Item Parkinson’s Disease Questionnaire (PDQ-39), EuroQol 5-Dimension Questionnaire (EQ-5D-5L) and the proportion of patients with morning akinesia. Morning akinesia was defined as reporting ‘Off’ status in PD diary as the predominant PD status during the first half-hour period upon awakening. 1
The safety analysis set included all patients who received at least one infusion of PRODUODOPA at any given time during the study. Efficacy was assessed in the full analysis set.
Overview of treatment-emergent adverse events (safety analysis set)1
| At 52 weeks | PRODUODOPA (N=244) |
AEs, n (%) | 230 (94.3) |
AEs associated with study drug, n (%) | 224 (91.8) |
Severe AEs,* n (%) | 63 (25.8) |
Serious AEs,* n (%) | 63 (25.8) |
AEs leading to discontinuation of study drug, n (%) | 64 (26.2) |
Deaths,†‡ n (%) | 3 (1.2) |
Adapted from Aldred J, et al. 2023.
Preferred terms classified using the Medical Dictionary for Regulatory Activities, version 24.0.
*While the values for severe AEs and serious AEs were the same, the patients reporting these events were not the same for each event. †There were a total of five deaths in the safety population; two were non-treatment-emergent (did not occur during study treatment or within 30 days of the last PRODUODOPA infusion); all were determined by investigators to be unrelated to the study drug. ‡Treatment-emergent deaths include subdural hematoma (most likely related to traumatic injury from an accidental fall) and cerebral mass effect, cardiorespiratory arrest, and cerebrovascular accident.
AEs of special interest1
| At 52 weeks | PRODUODOPA (N=244) |
Infusion site reactions, n (%) | 200 (82.0) |
Infusion site-related infections, n (%) | 86 (35.2) |
Falls and associated injuries, n (%) | 74 (30.3) |
Hallucinations/psychosis, n (%) | 61 (25.0) |
Weight loss, n (%) | 27 (11.1) |
Somnolence, n (%) | 12 (4.9) |
Polyneuropathy (narrow SMQ), n (%) | 8 (3.3) |
Adapted from Aldred J, et al. 2023.
Preferred terms classified using the Standardized Medical Dictionary for Regulatory Activities query (SMQ).
Most frequent (>10%) AEs1
| At 52 weeks | PRODUODOPA (N=244) |
Infusion site erythema, n (%) | 127 (52.0) |
Infusion site nodule, n (%) | 70 (28.7) |
Infusion site cellulitis, n (%) | 56 (23.0) |
Infusion site oedema, n (%) | 47 (19.3) |
Hallucination, n (%) | 42 (17.2) |
Fall, n (%) | 41 (16.8) |
Infusion site pain, n (%) | 38 (15.6) |
Infusion site reaction, n (%) | 30 (12.3) |
Anxiety, n (%) | 29 (11.9) |
Infusion site abscess, n (%) | 27 (11.1) |
Dizziness, n (%) | 25 (10.2) |
Adapted from Aldred J, et al. 2023.
SAEs occurring in >2 patients1
| At 52 weeks | PRODUODOPA (N=244) |
Infusion site cellulitis, n (%) | 10 (4.1) |
Infusion site abscess, n (%) | 8 (3.3) |
Hallucination, n (%) | 7 (2.9) |
Parkinson’s disease, n (%) | 6 (2.5) |
Psychotic disorder, n (%) | 6 (2.5) |
Urinary tract infection, n (%) | 4 (1.6) |
Sepsis, n (%) | 3 (1.2) |
Pneumonia, n (%) | 3 (1.2) |
Adapted from Aldred J, et al. 2023.
AE: Adverse Event
Efficacy endponts1
Efficacy endpoints were summarised using descriptive statistics. P values throughout this study are nominal and therefore no clinical conclusions can be drawn from this data. 1
Average daily normalised ‘Off’ time and ‘On’ time
The mean daily normalised ‘Off’ time for patients on PRODUODOPA was 5.9 hours (SD 2.2) at baseline. The mean daily normalised ‘On’ time without dyskinesia was 6.5 hours (SD 3.4) at baseline. The mean daily normalised ‘On’ time with non-troublesome dyskinesia was 2.6 hours (SD 2.6) at baseline. The mean daily normalised ‘On’ time with troublesome dyskinesia was 1.0 hours (SD 1.7) at baseline. The mean daily normalised ‘On’ time without troublesome dyskinesia was 9.1 hours (SD 2.5) at baseline.
CI=confidence interval; EQ-5D-5L=EuroQol 5-Dimension Questionnaire; IR=immediate release; LD/CD=levodopa/carbidopa; LS=least squares; MDS-UPDRS=Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; PDQ-39=39-Item Parkinson’s Disease Questionnaire; PD=Parkinson’s disease; PDSS-2=Parkinson’s Disease Sleep Scale-2; SD=standard deviation; SE=standard error; SMQ=Standardized Medical Dictionary for Regulatory Activities query.
References
- Aldred J, et al. Neurol Ther. 2023 Aug 26. doi: 10.1007/5. s40120-023-00533
IL-PRODD-240009. Date of preparation: July 2024.
Study design1
Duration: 52 weeks.
Study type: 52-week, phase 3, open-label, single-arm, multicentre study conducted at 60 sites across 13 countries (Australia, Belgium, Canada, Denmark, Germany, Italy, Japan, Netherlands, Russia, Spain, Sweden, United Kingdom, and United States of America).
Patient population: Patients aged at ≥30 years with a diagnosis of idiopathic and levodopa-responsive Parkinson’s disease (PD). Before initiation of PRODUODOPA, patients must have had symptoms that, in the investigator’s opinion, were not adequately controlled by their current therapy, and must have experienced an average of ≥2.5 hours of ‘Off’ time per day, as assessed by the electronic PD diary over two consecutive days prior to day 1 (study enrollment).
Aim: To assess to assess the safety, tolerability, and efficacy of PRODUODOPA administered as a 24-hour/day continuous subcutaneous infusion (CSCI) in patients with PD whose motor symptoms were inadequately controlled by their current treatment.
Methods: Of the 244 patients treated with PRODUODOPA, 137 completed the study and 107 prematurely discontinued treatment with PRODUODOPA.
