Status:
Not Yet Recruiting
Clinicaltrials.gov identifier:
Sponsor:
Cerevel Therapeutics, LLC
Enrollment:
368
Study Design:
This is a phase 3, double-blind, randomized, placebo-controlled, parallel-group, flexible-dose, 27-week trial designed to evaluate the efficacy, safety, and tolerability of tavapadon as adjunctive therapy in advanced PD participants already on levodopa and with motor fluctuations. The inclusion criteria for TEMPO-3 is different to TEMPO-1 and 2 for obvious reasons. It will include clinically diagnosed PD participants between age 40-80 years with “on” state H&Y stage between 2–3. Participants should be levodopa responsive, taking at least 400mg/day and be on a stable dose for at least four weeks before screening. Other adjunctive therapies are allowed if started >90 days before signing the consent and is expected to be stable throughout the study. Standard exclusionary criteria apply. Participants from prior tavapadon trial will be excluded.
This study has two arms: 1. Experimental arm where participants will be randomized to receive tavapadon anywhere from 5 to 15mg daily for 27 weeks; 2. Placebo comparator arm where participants will receive a placebo for 27 weeks. The study is being conducted at 21 sites across the USA.
Rationale:
All the measures will assess the change from baseline. The primary outcome will assess the change in the total “on” time without troublesome dyskinesia based on the Hauser diary entries at 27 weeks. The secondary outcomes will measure the following: 1. Change in the total ‘Off’ times at 27 weeks; 2. Change in total “on” and “off” times without troublesome dyskine-sia at weeks 2, 5, 8, 11, 14, 18, 22, 26, and 27; and 3. Change in MDS-UPDRS part I, II, and III individual scores at 27 weeks.
Comments:
Tavapadon is an exciting molecule with the potential for therapeutic benefit by modulating the direct pathways in the basal ganglia circuitry. However, the drug has had a few setbacks in phase 2 studies. The advanced stage of the disease and fixed medication dose may account for the lack of efficacy in the interim analysis of NCT02687542. TEMPO-3, likely learning from phase 2 results, will study the molecule as adjunctive therapy with flexible dosing. Notably, the NCT02847650 trial showed a safe profile with a positive change in motor scoring in early PD, but the results were not clinically meaningful. Given the results were from a Phase 2 study with partial data analysis, we will be on the lookout for TEMPO-1 and 2 study results. While D1R is a potential target for PD-CI, TEMPO studies do not include any secondary cognitive measures and exclude participants with MoCA less <26 for early PD and those with troublesome CI in advanced PD. Their focus remains on the motor profile of PD.
