Objective: To evaluate motor improvements in adults with early Parkinson’s disease (PD) who initiated levodopa (LD) during phase 3 trials of tavapadon.

Background: Tavapadon, an oral, once-daily, selective D1/D5 partial agonist, improved PD symptoms with a favorable safety profile in people with early PD (TEMPO-1 [NCT04201093]; TEMPO-2 [NCT04223193]) and exhibited sustained efficacy in TEMPO-4 (NCT04760769). Sustained PD symptom control with tavapadon (without LD) may delay oral LD initiation, reducing the risk of LD-induced dyskinesias and other motor complications.

Method: Participants with early PD (<3 years’ duration) received fixed-dose tavapadon (5 or 15 mg; TEMPO-1), flexible-dose tavapadon (5-15 mg; TEMPO-2), or placebo once daily for 27 weeks. LD-naive participants from TEMPO-1 and TEMPO-2 then enrolled in TEMPO-4, allowing oral LD initiation if needed. Motor function was assessed via Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III scores. This post hoc analysis evaluated improvements in motor function.

Results: Of 520 TEMPO-1 participants, 39 (7.5%) initiated oral LD (originally randomized to placebo, n=18; tavapadon 5 mg, n=14; tavapadon 15 mg, n=7) during the 58-week trial. Of 301 TEMPO-2 participants, 11 (3.6%) initiated oral LD (placebo, n=5; tavapadon 5-15 mg, n=6). While baseline characteristics were mostly similar between LD initiator and noninitiator groups, mean (standard deviation) MDS-UPDRS Part III scores were numerically higher for LD initiators versus noninitiators rolled over from TEMPO-1 (29.1 [10.4] vs 24.0 [8.3]) and TEMPO-2 (30.5 [11.5] vs 23.1 [8.5]). A greater proportion of LD initiators versus noninitiators had modified Hoehn and Yahr stage 2 at screening from TEMPO-1 (87.2% vs 68.8%) and TEMPO-2 (81.8% vs 60.2%). At week 58, changes from baseline in MDS-UPDRS Part II and III individual scores were similar between LD initiators and noninitiators in both trials [figure 1] [figure 2].

Conclusion: Less than 8% of those treated with tavapadon initiated LD during the 58-week, open-label follow-up. Tavapadon responses were similar for LD initiators versus noninitiators; those worse at baseline may be more likely to need LD. Subtle differences between groups may reflect treatment pattern differences of healthcare providers and their threshold for LD initiation.

Figure 2

Figure 1

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-initiation-in-phase-3-trials-of-tavapadon-a-selective-d1-d5-agonist-for-early-parkinsons-disease/