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Produodopa® 12-Week Efficacy and Safety Study: Clinical Profile2
A 12-week Phase 3 randomised, double-blind, double-dummy, active-controlled study comparing the efficacy and safety of Produodopa® to oral IR levodopa/carbidopa in patients with advanced PD.
Of the 74 patients receiving Produodopa®, 48 completed the study.
Of the 67 patients receiving optimised oral IR levodopa/carbidopa, 62 completed the study.
IR=immediate-release; PD=Parkinson's disease.
(LS mean of difference=1.75 hours; P=0.0083)
*Based on the PD Diary, the average daily normalised “On” time without troublesome dyskinesia for patients on Produodopa® was 9.20 (+/−2.42) hours at baseline and increased by 2.72 (+/−0.52) hours at Week 12 compared with an increase of 0.97 (+/−0.50) hours at Week 12 from a baseline of 9.49 (+/−2.62) hours for patients taking optimised oral IR levodopa/carbidopa (LS mean change [SE]). This resulted in a statistically significant increase of 1.75 (+/−0.65) hours in patients on Produodopa® vs oral IR LD/CD (LS mean of difference [SE]; P=0.0083). "On" time without troublesome dyskinesia is the sum of "On" time without dyskinesia and "On" time with non-troublesome dyskinesia.
IR=immediate-release; LD/CD=levodopa/carbidopa; LS=least squares; PD=Parkinson's disease; SE=standard error.
Produodopa® provided a superior improvement in daily “Off” time vs oral IR levodopa/carbidopa2
(LS mean of difference=1.79 hours; P=0.0054)
*Based on the PD Diary, the average daily normalised “Off” time for patients on Produodopa® was 6.34 (+/−2.27) hours at baseline and decreased by 2.75 (+/−0.50) hours at Week 12 compared with a decrease of 0.96 (+/−0.49) hours at Week 12 from a baseline of 5.91 (+/−1.88) hours for patients taking optimised oral IR levodopa/carbidopa (LS mean change [SE]). This resulted in a statistically significant reduction of 1.79 (+/−0.63) hours in patients on Produodopa® vs oral IR LD/CD (LS mean of difference [SE]; P=0.0054).
IR=immediate-release; LD/CD=levodopa/carbidopa; LS=least squares; PD=Parkinson's disease; SE=standard error.
Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.1,2
*Morning akinesia was defined as reporting “Off” status as the first morning symptom upon awakening.
†Percentage of patients without morning akinesia is the sum of patients reporting "On" time without dyskinesia, "On" time with non-troublesome dyskinesia, and “On” time with troublesome dyskinesia upon awakening.
‡For patients on Produodopa®, based on PD Diary, “On” time without dyskinesia was reported in 70% (N=33/47) of patients; “On” with non-troublesome dyskinesia in 8% (N=4/47) of patients; “On” with troublesome dyskinesia was reported in 4% (N=2/47) of patients at Week 12. For patients on oral IR LD/CD, based on the PD Diary, “On” time without dyskinesia was reported in 37% (N=22/66) of patients at Week 12. For patients on Produodopa®, based on the PD Diary, morning akinesia was reported in 79% (N=56/71) of patients at baseline and in 17% (N=8/47) of patients at Week 12. For patients on oral IR LD/CD, based on the PD Diary, morning akinesia was reported in 76% (N=51/67) of patients at baseline and in 63% (N=38/60) of patients at Week 12.
IR=immediate-release; LD/CD=levodopa/carbidopa; PD=Parkinson's disease; QoL=quality of life.
Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.1,2
Change from baseline to Week 12 in PDSS-2 total score2*
*For patients on Produodopa® the PDSS-2 total score was 21.19 (+/-8.80) (N=72) at baseline with a change of -7.92 (+/-1.18) (n=44) at Week 12. For patients on oral IR LD/CD the PDSS-2 total score was 18.88 (+/-9.25) (N=66) at baseline with a change of -2.52 (+/- 1.12) (n=59) at Week 12.
IR=immediate-release; LD/CD=levodopa/carbidopa; PDSS-2=Parkinson's Disease Sleep Scale-2; QoL=quality of life; SD=standard deviation.
Select secondary efficacy endpoints including motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, among others, were tested in hierarchical order and did not meet statistical significance based on the hierarchical testing procedure.1,2
Change from baseline to Week 12 in PDQ-39 summary index2*
*For patients on Produodopa® the mean (SD) PDQ-39 summary index value was 30.68 (+/-16.05) (N=73) at baseline with a change of -6.38 (+/-1.83) (n=45) at Week 12. For patients on oral IR LD/CD the mean (SD) PDQ-39 summary index value was 26.15 (+/-14.46) (N=66) at baseline with a change of -2.28 (+/- 1.75) (n=59) at Week 12.
IR=immediate-release; LD/CD=levodopa/carbidopa; PDQ-39=39-item Parkinson's Disease Questionnaire; QoL=quality of life; SD=standard deviation.
Produodopa® and pill burden
Since the study design required concomitant PD medications to remain stable, further investigation is needed to fully assess the potential of Produodopa® to reduce or eliminate the simultaneous use of concomitant PD medications.2
HCP=healthcare professional; PD=Parkinson's disease.
Produodopa® 52-Week Safety Study: Clinical Profile3
A 52-week, 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.
Of the 244 patients receiving Produodopa®, 137 completed the study
PD=Parkinson's disease
*"On" time without troublesome dyskinesia is the sum of "On" time without dyskinesia and "On" time with non-troublesome dyskinesia.
†For patients on Produodopa®, based on the PD Diary, the average "On" time without troublesome dyskinesia was 9.1 hours (N=236) at baseline with a change of 3.8 hours (average 13.1 hours) (n=116) at Week 52.
‡52-week value is the sum of 10.8 ("On" time without dyskinesia) and 2.3 ("On" time with non-troublesome dyskinesia).
PD=Parkinson's disease.
At Week 52 Produodopa® provided less daily "Off" time vs baseline3
*"Off” time was decreased by an average of 3.5 hours by Week 52 (average 2.5 hours) compared to baseline (average 5.9 hours) as demonstrated by a the average daily normalised "Off" time for patients in their PD Diaries from baseline to study end (n=116).
PD=Parkinson's disease.
WHY PRODUODOPA?
CLINICAL PROFILE
SAFETY
INITIATION & CUSTOMISATION
- Produodopa® (foslevodopa/foscarbidopa solution for infusion) Summary of Product Characteristics, available on www.medicines.ie.
- Soileau MJ, et al. Lancet Neurol. 2022; 21:1099–1109 (incl. suppl.).
- Aldred J, Freire-Alvarez E, Amelin AV, et al. Neurol Ther 2023;12:1937–1958. (incl. suppl.).
IE-PRODD-230026 Date of preparation: August 2024.
Produodopa® 12-week efficacy and safety study endpoints2
Secondary effcacy endpoints were tested in a hierarchical order.
*"On" time without troublesome dyskinesia is the sum of "On" time without dyskinesia and "On" time with non-troublesome dyskinesia.
†Based on PD Diary (normalized to a 16-hour waking day and averaged over 3 consecutive days).
‡MDS-UPDRS Part II score. §Morning akinesia is defined as reporting "Off" status as the first morning symptom on waking.
||EQ-5D-5L summary index is based on the weighted scoring algorithm for the United States.
EQ-5D-5L=EuroQol 5-Dimension Questionnaire; IQR=interquartile range; MDS-UPDRS=Movement Disorder Society—Unified Parkinson’s Disease Rating Scale; PD=Parkinson's disease; PDQ-39=39-item Parkinson’s Disease Questionnaire; PDSS-2=Parkinson’s Disease Sleep Scale-2; PKG=Parkinson’s KinetiGraph or Personal KinetiGraph (Global Kinetics, MN, USA).
Sleep Data from 52 week Safety Study3
PDSS-2 is a secondary efficacy endpoint of this 52-week, phase 3, open-label, single arm, multicenter study
Change from baseline to Week 52 in PDSS-2 total score*
*For patients on Produodopa® the PDSS-2 total score was 20.4 (N=243) at baseline with a change of -7.5 (+/-10.8) (n=131) at Week 52.
PDSS-2=Parkinson's Disease Sleep Scale-2; SD=standard deviation.
Produodopa® 52-week safety study endpoints3
*From initiation of continuous subcutaneous infusion (CSCI) through 30 days after last infusion device was removed (up to 56 weeks).
†The Infusion-Site Evaluation Scale, a 2-part numeric (0–7) and letter (A–G) grade scale, where 7 and G indicated the worst outcomes, was used to assess skin tolerability.
‡PD Diary.
§Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-IV (with Part III measured in the patient's best "On" state).
||Parkinson’s Disease Sleep Scale-2 (PDSS-2) total score.
¶PD Questionnaire-39 items (PDQ-39).
#EuroQol 5-Dimension Questionnaire (EQ-5D-5L).
**Percentage of subjects with early morning “Off” status based on the first morning symptom upon awakening derived from PD Diary.
PD=Parkinson's disease.
