TEMPO-1
(2026)Objective
To evaluate the efficacy, safety, and tolerability of fixed-dose tavapadon, an oral once-daily selective D1/D5 partial agonist, in adults with early Parkinson disease.
Study Summary
• Tavapadon 15 mg also significantly reduced MDS-UPDRS parts II+III combined score (treatment difference −12.1 points; 95% CI, −14.4 to −9.8; P<.001; d=1.20)
• Favorable safety profile; most AEs were mild to moderate; common AEs were nausea (25.4%), headache (16.7%), and dizziness (12.7%)
Intervention
Tavapadon 5 mg or 15 mg once daily vs placebo for 27 weeks, with titration to target dose
Inclusion Criteria
Adults aged 40-80 years with early Parkinson disease (<3 years' disease duration), modified Hoehn and Yahr stage 1, 1.5, or 2, treatment naive or <3 months prior dopaminergic treatment
Study Design
Arms: Tavapadon 5 mg once daily (n=177) vs Tavapadon 15 mg once daily (n=177) vs Placebo (n=175)
Patients per Arm: 177 vs 177 vs 175
Outcome
• Treatment differences: −11.5 points (5 mg; P<.001; d=1.14) and −12.1 points (15 mg; P<.001; d=1.20)
• Discontinuation rates: 15.4% (placebo), 24.3% (5 mg), 33.3% (15 mg); most common AEs were nausea, headache, dizziness
Bottom Line
In adults with early Parkinson disease, both fixed doses of tavapadon (5 mg and 15 mg once daily) produced clinically meaningful improvements in motor function (MDS-UPDRS parts II+III) with an acceptable safety profile, supporting tavapadon as a potential alternative to conventional D2/D3 dopamine agonists.
Major Points
- Both tavapadon 5 mg and 15 mg significantly improved MDS-UPDRS parts II+III combined scores at week 26 vs placebo (treatment differences −11.5 and −12.1 points, respectively; both P<.001)
- Large effect sizes (Cohen's d = 1.14 for 5 mg; d = 1.20 for 15 mg) suggest clinically meaningful motor improvement
- Tavapadon-treated participants showed a ~9.7-10.2 point decrease in MDS-UPDRS parts II+III, while placebo participants worsened by 1.8 points
- Most common adverse events were nausea (25.4%), headache (16.7%), and dizziness (12.7%); most AEs were mild to moderate
- Premature discontinuation was higher with tavapadon (24.3% at 5 mg, 33.3% at 15 mg) than placebo (15.4%), driven largely by adverse events
- Tavapadon represents the first selective D1/D5 agonist evaluated in phase 3 for early PD, offering a mechanistically distinct alternative to existing dopaminergic therapies
Study Design
- Study Type
- Phase 3, prospective, multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial
- Randomization
- Yes
- Blinding
- Double-blind (participants, investigators, and blinded sponsor personnel remained blinded until final database lock); identical-appearing tablets and packaging
- Sample Size
- 529
- Follow-up
- 27-week treatment period followed by 4-week safety follow-up (total ~34 weeks including screening)
- Centers
- 102
Primary Outcome
Definition: Least-squares mean change from baseline to week 26 in MDS-UPDRS parts II and III combined score
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 1.8-point increase (worsening) with placebo | 9.7-point decrease with tavapadon 5 mg; 10.2-point decrease with tavapadon 15 mg | - (5 mg vs placebo: −13.8 to −9.2; 15 mg vs placebo: −14.4 to −9.8) | <.001 (both doses vs placebo) |
Limitations & Criticisms
- Predominantly White population (97.2%) limits generalizability across racial/ethnic groups
- Higher discontinuation rates in tavapadon arms (24-33%) vs placebo (15%) raise tolerability concerns over longer-term use
- 27-week treatment period is relatively short for a chronic, progressive disease; long-term durability and dyskinesia risk remain to be established
- No active comparator (e.g., levodopa or conventional D2/D3 dopamine agonist) — comparative efficacy/safety cannot be determined from this trial alone
- Fixed-dose design without individual titration may not reflect real-world clinical practice
Citation
JAMA Neurol. 2026;83(5):452-460. doi:10.1001/jamaneurol.2026.0590