Drug Update · Neurology

TEMPO-3: Tavapadon Increases Good‑On‑Time 1.10 Hours in PD

July 16, 2026

Primary endpoint (good-on-time difference)

1.10 hours (1.70 vs 0.60 hours; 95% CI, 0.60-1.70; P < .001)

Daily off-time difference

-0.94 hours (change from baseline -1.88 vs -0.93 hours; 95% CI, -1.48 to -0.41; P < .001)

Participants randomized

507

Common adverse events (tavapadon)

Nausea 14.3%; Dyskinesia 10.0%; Dizziness 7.6%

Overall AE rates

71.7% with tavapadon vs 55.1% with placebo; 93.2% of AEs nonserious

Trial identifier

NCT04542499

Clinical Perspective

Clinicians caring for adults with Parkinson disease who experience motor fluctuations while receiving stable oral levodopa are the primary population affected by these data. The TEMPO-3 results support that adjunctive tavapadon increased daily good-on-time by 1.10 hours and reduced daily off-time by 0.94 hours versus placebo in this population ^[1]. How tavapadon’s adverse-event profile and comparative tolerability versus existing D2/D3-preferring adjunctive dopamine agonists will perform in broader clinical practice remains an open question?

Dr. Vikram Patel · Neurology

Tavapadon, an investigational oral selective D1/D5 receptor agonist, increased total daily good-on-time by 1.10 hours versus placebo in the phase 3 TEMPO-3 randomized clinical trial of adults with Parkinson disease (PD) experiencing motor fluctuations ^[1]. The trial also showed a between-group difference in daily off-time of -0.94 hours favoring tavapadon (P < .001) ^[1].

Clinical Context

Development of motor fluctuations is common in people with PD treated with oral levodopa, and currently available dopamine agonists adjunctive to levodopa offer additional motor control but may increase risk of adverse events via preferential activation of D2/D3 receptors, the authors note ^[1]. Tavapadon is described in the report as a novel, investigational, oral, once-daily, selective D1/D5 agonist intended as adjunctive therapy to oral levodopa for motor fluctuations in PD ^[1]. The TEMPO-3 publication lists academic and industry collaborators and frames the drug as an alternative approach to dopamine-receptor targeting in fluctuating PD patients receiving levodopa ^[1].

Key Findings

The TEMPO-3 randomized clinical trial showed tavapadon increased total daily good-on-time by 1.10 hours versus placebo (1.70 vs 0.60 hours; 95% CI, 0.60-1.70; P < .001) in adults with PD experiencing motor fluctuations adjunctive to oral levodopa ^[1].
The trial also showed a significant reduction in total daily off-time with tavapadon versus placebo: change from baseline -1.88 vs -0.93 hours; difference -0.94 hours (95% CI, -1.48 to -0.41); P < .001 ^[1].
Enrollment and analysis included 507 randomized participants; the results were based on outcomes through week 26 with a 4-week safety follow-up reported in the publication ^[1].

Safety & Tolerability

Overall adverse events occurred in 180 participants (71.7%) with tavapadon versus 140 participants (55.1%) with placebo; most were nonserious (93.2%) and mild to moderate in severity ^[1].
Common adverse events reported with tavapadon (incidence ≥5%) were nausea (14.3%), dyskinesia (10.0%), and dizziness (7.6%) ^[1].
Safety information in the trial report is limited to the named adverse events and summary rates above; no additional safety monitoring recommendations or long-term safety data were provided in the provided source excerpts ^[1].

Study Design

TEMPO-3 was a phase 3, double-blind, placebo-controlled randomized clinical trial conducted between September 2020 and February 2024 with a 4-week safety follow-up ^[1]. Participants were adults with PD experiencing motor fluctuations while receiving stable oral levodopa (≥400 mg daily) and were randomized 1:1 to flexible-dose tavapadon (5-15 mg once daily) or placebo adjunctive to levodopa for 27 weeks across 148 sites in 14 countries; 507 participants were enrolled and treated ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The prespecified primary end point was change from baseline to week 26 in total daily good-on-time; a key secondary end point was change from baseline in total daily off-time ^[1].

FAQ

Q1 What did the TEMPO-3 trial show?

The TEMPO-3 randomized clinical trial showed that tavapadon, given adjunctive to oral levodopa, increased total daily good-on-time by 1.10 hours compared with placebo (1.70 vs 0.60 hours; 95% CI, 0.60-1.70; P < .001) and reduced daily off-time by -0.94 hours versus placebo (difference -0.94 hours; 95% CI, -1.48 to -0.41; P < .001) in adults with Parkinson disease experiencing motor fluctuations. The trial enrolled 507 participants and included a 27-week treatment period with a 4-week safety follow-up.

Q2 Who was enrolled in TEMPO-3?

TEMPO-3 enrolled adults with Parkinson disease who were experiencing motor fluctuations while receiving stable oral levodopa of at least 400 mg daily. Participants were randomized 1:1 to flexible-dose tavapadon (5-15 mg once daily) or placebo across 148 sites in 14 countries; 507 participants received study treatment and were included in the reported analyses.

Q3 What were the side effects reported in TEMPO-3?

Adverse events were reported more frequently with tavapadon than placebo (180 participants [71.7%] vs 140 participants [55.1%]), and most events were nonserious (93.2%) and mild to moderate in severity. The most common adverse events with tavapadon (incidence ≥5%) were nausea (14.3%), dyskinesia (10.0%), and dizziness (7.6%).

Q4 What does TEMPO-3 mean for clinical practice?

TEMPO-3 provides randomized phase 3 evidence that adjunctive tavapadon can increase daily good-on-time and reduce daily off-time versus placebo in adults with PD experiencing motor fluctuations on levodopa, indicating potential symptomatic benefit from a selective D1/D5 agonist approach. Confirmation of comparative effectiveness and longer-term safety versus established adjunctive agents will be needed to define tavapadon’s place in therapy.

Clinicians should consult current prescribing information for full dosing guidance.

References

PubMed — Primary trial publication (PMID 41860544)

TEMPO-3: Tavapadon Increases Good‑On‑Time 1.10 Hours in PD

Direct Clinical Takeaway & Evidence Summary

TEMPO-3: Tavapadon Increases Good‑On‑Time 1.10 Hours in PD

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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