Trial objective: long-term safety and efficacy of flexible-dose tavapadon

“The purpose of this study is to evaluate the safety and efficacy of long-term administration of flexible doses of tavapadon in participants with Parkinson's Disease.” (opens the source at this quote in a new tab)

Objective as stated in the interim analysis

“The TEMPO-4 trial (NCT04760769) evaluated the long-term safety and efficacy of tavapadon in adults with PD.” (opens the source at this quote in a new tab)

Role of TEMPO-4 in the new drug application

“The submission is also based on an interim data cut from TEMPO-4, an open-label extension (OLE) trial to assess the long-term clinical benefit of tavapadon.” (opens the source at this quote in a new tab)

Summary: sponsor, identifiers, sites, and study dates

The registry record for NCT04760769 gives AbbVie as lead sponsor, CVL-751-PD-004 as the sponsor protocol number, and 2019-002952-17 as the EudraCT number. The actual study start date was 24 February 2021, and the actual primary completion and study completion dates were both 1 December 2025; the overall status is completed. The record lists 140 study locations in 14 countries: the United States (52 sites), Poland (12), Spain (11), Italy (10), Germany (9), Bulgaria (7), France (7), Ukraine (7), Australia (6), Czechia (5), Israel (5), Serbia (4), Hungary (3), and Canada (2). As of September 2026, no results had been posted to the registry.

Presentation of the interim analysis

“The interim analysis, presented as a late-breaker at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, included 468 patients who rolled over, and 524 previously untreated participants (placebo rollover: n = 471; de novo; n = 53).” (opens the source at this quote in a new tab)

Open-label design, treatment duration, and follow-up

“Participants who completed the TEMPO-1, TEMPO-2, or TEMPO-3 trial, as well as newly enrolled participants with PD (modified Hoehn and Yahr stage 1, 1.5, 2, 2.5, or 3) on a stable dose of levodopa were enrolled in the phase 3, open-label TEMPO-4 trial. Participants received tavapadon (5 to 15 mg once daily) for up to 58 weeks (85 total weeks of exposure for those who had previously received tavapadon in the TEMPO-1, -2, and -3 trials), followed by a 10-day safety/withdrawal assessment period and 20-day safety follow-up period.” (opens the source at this quote in a new tab)

Registry design record

Design element	Quoted record
Official title	“58-Week Open-label Trial of Tavapadon in Parkinson's Disease (TEMPO-4 Trial)”
Phase	“Phase 3”
Enrollment (actual)	“992”

Source cohorts described by the sponsor

“An open-label extension study (TEMPO-4) is ongoing to assess the long-term safety and efficacy of tavapadon through 58 weeks of treatment. TEMPO-4 enrolled patients who completed participation in TEMPO-1 through 3, as well as patients on stable doses of levodopa who had not been in prior TEMPO trials.” (opens the source at this quote in a new tab)

Summary: age and sex eligibility

The registry record sets an age range of 40 to 80 years, accepts participants of all sexes, and does not accept healthy volunteers.

Inclusion criteria for rollover participants

“Participants who complete the 27-week double-blind Treatment Period of Trial CVL-751-PD-001 (NCT04201093) or Trial CVL-751 PD-003 (NCT04542499) or the 27-week double-blind Treatment Period and 10-day Safety/Withdrawal Assessment Period of Trial CVL-751-PD-002 (NCT04223193) and enter this trial within 72 hours after completing the last trial visit in the double-blind trial. Rollover participants from Trial CVL-751-PD-003 must continue to use levodopa/carbidopa (or levodopa/benserazide) for the duration of the trial.” (opens the source at this quote in a new tab)
“Participants who are willing and able to refrain from any PD medications that are not permitted by the protocol (including dopaminergic agents) throughout participation in the trial.” (opens the source at this quote in a new tab)

Exclusion criteria for rollover participants

“Participants who do not enroll in this open-label trial within 72 hours after completing the last trial visit in the double-blind trial” (opens the source at this quote in a new tab)
“Participants who had previously been enrolled in this open-label trial and had subsequently withdrawn.” (opens the source at this quote in a new tab)

Newly enrolled participants

“newly enrolled participants with PD (modified Hoehn and Yahr stage 1, 1.5, 2, 2.5, or 3) on a stable dose of levodopa” (opens the source at this quote in a new tab)

Tavapadon dose and duration

“Participants will receive a Tavapadon tablet at a dose of 5 milligrams (mg) to 15 mg once daily (QD) orally during 58-week treatment period.” (opens the source at this quote in a new tab)

Levodopa use by source cohort

“The TEMPO-4 trial enrolled levodopa-naive participants from TEMPO-1 and TEMPO-2, participants receiving stable levodopa treatment from TEMPO-3, and de novo participants receiving stable levodopa treatment.” (opens the source at this quote in a new tab)

Safety outcome measures

“Number of Participants With Treatment Emergent Adverse Events (TEAEs)” (opens the source at this quote in a new tab)
“Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE). Clinically significant abnormalities in Clinical Laboratory Evaluations, Vital Signs, Physical and Neurological evaluations and ECGs will be reported as TEAEs.” (opens the source at this quote in a new tab)
“Number of Participants Who Discontinued Study Treatment” (opens the source at this quote in a new tab)

Impulse control, sleepiness, suicidality, and withdrawal assessments

“QUIP-RS is a global screening instrument that assesses impulse control disorders (ICDs) and related disorders (punding, hobbyism, and dopamine dysregulation syndrome) in participants with PD.” (opens the source at this quote in a new tab)
“ESS is a scale that is intended to measure daytime sleepiness.” (opens the source at this quote in a new tab)
“C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent."” (opens the source at this quote in a new tab)
“SMWQ is a questionnaire to assess withdrawal symptoms subsequent to completion of dosing with Investigational medicinal product (IMP).” (opens the source at this quote in a new tab)

Efficacy outcome measures

“Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II and III” (opens the source at this quote in a new tab)
“Change From Baseline in the Hauser diary” (opens the source at this quote in a new tab)
“Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Index” (opens the source at this quote in a new tab)

Outcome time frames

“62 Weeks” (opens the source at this quote in a new tab)
“58 Weeks” (opens the source at this quote in a new tab)
“Baseline (Day 1), Weeks 32 and 58” (opens the source at this quote in a new tab)

Participants enrolled by source cohort

“Of 992 enrolled participants, 468 had previously received tavapadon in the TEMPO-1, -2, and -3 trials; 524 were previously untreated (placebo rollover, n=471; newly enrolled, n=53).” (opens the source at this quote in a new tab)

Pooled safety population in the interim analysis

“Pooling both cohorts (n = 991)” (opens the source at this quote in a new tab)

Post hoc levodopa analysis populations

“This TEMPO-4 post hoc analysis assessed levodopa initiation in participants enrolled from TEMPO-1 and TEMPO-2 and levodopa dose adjustments in participants enrolled from TEMPO-3 and de novo participants.” (opens the source at this quote in a new tab)

Completion, ongoing treatment, and discontinuation at the interim analysis

“In this interim analysis, 484 (48.8%) participants completed the study, 223 (22.5%) were receiving treatment, and 285 (28.7%) discontinued treatment. Adverse events (AEs; n=136 [13.7%]) and withdrawal by subject (n=71 [7.2%]) were the most common reasons for treatment discontinuation.” (opens the source at this quote in a new tab)

Data cutoff of the interim analysis

“less than half (48.8%) of the participants completed the trial as of October 25, 2024, while 28.7% (n = 285) discontinued treatment and 22.5% (n = 223) were still on the study drug” (opens the source at this quote in a new tab)

Prior treatment in the antecedent trials

“468 had previously received tavapadon in the TEMPO-1, -2, and -3 trials; 524 were previously untreated (placebo rollover, n=471; newly enrolled, n=53)” (opens the source at this quote in a new tab)

Demographic and disease characteristics at open-label baseline

No evidence found.

Motor function with continued treatment

“Participants who received tavapadon in the TEMPO-1, -2, and -3 trials had stable improvements in motor function with continued tavapadon treatment. Placebo rollover and de novo participants showed motor improvements, which remained stable with continued treatment over 58 weeks.” (opens the source at this quote in a new tab)
“This interim analysis demonstrated that tavapadon has a favorable long-term safety profile and provides stable efficacy with continued treatment.” (opens the source at this quote in a new tab)

Levodopa initiation in the early Parkinson's disease cohorts (post hoc)

“In the early PD cohorts (TEMPO-1 and TEMPO-2 extensions), most participants (86.4% to 94.0%) avoided initiating levodopa over the treatment period (previously treated, 85 weeks of treatment; previously untreated, 58 of weeks treatment).” (opens the source at this quote in a new tab)

Levodopa dose changes in the adjunctive cohorts (post hoc)

“For those already receiving tavapadon adjunctive to levodopa (TEMPO-3 extension or newly enrolled participants), the drug rarely necessitated dose adjustments. Most patients (81.3% to 87.6%) kept their levodopa dose stable. When modifications were needed, patients were twice as likely to reduce their levodopa dose (∼10%) than to increase it (∼5%), keeping the mean daily dose under 1000 mg.” (opens the source at this quote in a new tab)
“After a total of 14-20 months of tavapadon treatment, ~90% of participants did not require levodopa initiation or dose increases.” (opens the source at this quote in a new tab)

MDS-UPDRS and Hauser diary values by cohort

No evidence found.

EuroQol 5 Dimension 5 Level as a prespecified outcome measure

“Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Index” (opens the source at this quote in a new tab)
“Change From Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scores (VAS)” (opens the source at this quote in a new tab)

Reported patient-reported outcome results

No evidence found.

Overall safety profile at the interim analysis

“The safety profile was consistent with previous studies; most AEs were non-serious and mild-to-moderate in severity (Table 1). There were low rates of AEs of interest , including AEs associated with currently approved D2/D3 receptor agonists. No new safety concerns were identified, including vital signs, laboratory/electrocardiogram results, or Columbia-Suicide Severity Rating Scale scores.” (opens the source at this quote in a new tab)

Most common treatment-emergent adverse events, pooled cohorts

“Pooling both cohorts (n = 991), the most common treatment-emergent adverse event (TEAE) observed with tavapadon was nausea (11.0%), followed by dizziness (10.6%), headache (9.6%), fall (9.2%), COVID-19 (9.1%), and constipation (5.5%).” (opens the source at this quote in a new tab)

Severity of treatment-emergent adverse events

“When pooling both patients who rolled over and de novo participants, mild, moderate, and severe TEAEs occurred in 29.5%, 36.3%, and 9.5% of patients.” (opens the source at this quote in a new tab)

Discontinuation due to treatment-emergent adverse events

“In the interim analysis, 14.1% of patients discontinued the study drug because of TEAEs.” (opens the source at this quote in a new tab)

Adverse events of special interest: hallucination, somnolence, hypotension, and impulse control disorders

“Outside of the aforementioned TEAEs, there were a few safety topics of special interest, including reports of hallucination (6.3%), somnolence (4.6%), hypotension (4.1%), orthostatic hypotension (3.7%), and impulse control disorders (1.4%).” (opens the source at this quote in a new tab)

Selectivity for D1/D5 receptors and adverse events of interest

“Selective D1/D5 agonism may offer a differentiated safety profile compared with D2/D3 agonists, as supported by the low rates of AEs of interest.” (opens the source at this quote in a new tab)

Pooled or integrated safety analyses across the TEMPO trials including TEMPO-4

No evidence found.

Summary: limitations of the available TEMPO-4 evidence

As of September 2026, TEMPO-4 results are available only from an interim analysis (data as of 25 October 2024) presented as a late-breaking abstract at the 2025 International Congress of Parkinson's Disease and Movement Disorders, a 2026 World Parkinson Congress abstract, a 2026 American Academy of Neurology abstract, and secondary news reports. The registry record lists the study as completed on 1 December 2025 but carries no posted results, and no peer-reviewed publication has been identified. The trial had a single open-label tavapadon arm with no control group, so the reported motor improvements and levodopa outcomes cannot be attributed to tavapadon by randomized comparison. Enrollment was drawn mainly from participants who completed the 27-week double-blind TEMPO-1, TEMPO-2, and TEMPO-3 trials, which may enrich the population for participants who tolerated treatment; 53 of 992 participants were newly enrolled. At the interim analysis, 285 participants (28.7%) had discontinued treatment, 136 (13.7%) because of adverse events. The levodopa analyses were post hoc. The abstracts report motor outcomes descriptively without MDS-UPDRS or Hauser diary values, and the adverse event table in the congress abstract is an image; the event rates quoted here come from a news report of the late-breaking presentation, which gives the pooled safety population as 991 participants and the rate of discontinuation due to adverse events as 14.1%, against 992 participants and 13.7% in the abstract.