Landmark 162 · Trial in people
TEMPO: rasagiline delayed start
Starting early left 404 people better off than starting late. But the design could not prove this was slowing the disease, not symptom relief.
In short
In 404 people with early Parkinson's, starting rasagiline right away left people better off than starting it six months later, a gap that lasted 6.5 years, but the design could not prove protection.
- What it is
- Trial in people
- Outcome
- Replaced by a newer approach
- When
- 2002–2009
- Size
- 404 people · Phase 3
- Approach
- Help cells clean up
- Research lane
- Oxidative stress
- Last checked
- 19 Oct 2026
The research record
This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".
Who
The Parkinson Study Group, at 32 sites in the US and Canada. First report 2002; delayed-start analysis 2004; 6.5-year follow-up by Robert Hauser and colleagues, 2009.
What happened
Rasagiline is a MAO-B inhibitor (it blocks an enzyme that breaks down dopamine), a cousin of deprenyl from landmark 61. Lab work suggested it might also protect neurons.
- 2002, 26 weeks. 404 people with early Parkinson's, not yet needing levodopa, took rasagiline 1 mg, 2 mg or placebo. UPDRS (a severity score, higher is worse) was 4.20 points better on 1 mg (95% CI 2.73 to 5.66) and 3.56 better on 2 mg (95% CI 2.08 to 5.04) than on placebo (both P<0.001). This is a symptom benefit.
- 2004, delayed start. After 6 months, placebo people were switched to rasagiline 2 mg. In the 371 people in the 12-month analysis, those on 2 mg all year had a 2.29-point smaller rise in UPDRS than those who started late (P=0.01); 1 mg all year was 1.82 points better than late start (P=0.05). The idea of the delayed-start design: if a drug only masks symptoms, the late starters should catch up. They did not fully.
- 2009, 6.5 years. 306 people continued in an open-label extension. Average time in the study was 3.6 years. Over the whole follow-up the early-start group was 2.5 UPDRS points better (P=0.021), or 16% (P=0.006), with better scores at every time point. Many people were also on other Parkinson's drugs by then.
Why it moved us toward a cure
This is the first large trial built to tell protection from symptom relief, a method the field reused for PROUD and LEAP (landmark 165, landmark 166). It also prompted the larger ADAGIO trial (landmark 62).
Outcome
Superseded. The delayed-start gap was suggestive, but ADAGIO (1,176 people), designed to confirm it, was met by the 1 mg dose only; the 2 mg dose did not differ between early and delayed start (P=0.60). On 17 October 2011 an FDA advisory committee voted 17–0 that Teva had not shown substantial evidence that rasagiline slows progression.
Sources
- Parkinson Study Group (TEMPO), Arch Neurol 2002;59:1937–1943, doi:10.1001/archneur.59.12.1937 (abstract via Europe PMC, PMID 12470183)
- Parkinson Study Group, Arch Neurol 2004;61:561–566, doi:10.1001/archneur.61.4.561 (PMID 15096406)
- Hauser et al., Mov Disord 2009;24:564–573, doi:10.1002/mds.22402 (PMID 19086083)
- Olanow et al. (ADAGIO), NEJM 2009;361:1268–1278, doi:10.1056/NEJMoa0809335 · FDA panel vote, MJFF 18 Oct 2011
- Not yet verified: the funders and registry ID of TEMPO; how many people in the 6.5-year analysis were on other dopaminergic drugs.
How it connects
Built on
- builds on DATATOP: deprenyl · 1987
Led to
- builds on ADAGIO: rasagiline · 2009
- uses PROUD: pramipexole delayed start · 2013