OAK has three phases, all open label. The first is a 26-week treatment phase, followed by a 156-week treatment extension and ending with a two-week follow up. The study is only open to those participants who complete the REDWOOD trial.
There are 10 primary outcome measures and no secondary ones, all compared to baseline at week 26: 1. Physical examination - number of subjects with new abnormalities; 2. Neurological examination - number of subjects with new abnormalities; 3. Vital Signs - number of subjects with clinically significant vital sign abnormalities; 4. ECG - number of subjects with clinically significant ECG findings; 5. Clinical laboratory tests - number of subjects with laboratory test abnormalities; 6. Changes in concomitant medications; 7. Adverse events (AEs) - incidence and severity of treatment-emergent adverse events; 8. Subject compliance to study treatment - number of subjects determined to be compliant with study medications; 9. Changes in incidence of falls; 10. Changes from baseline in Columbia Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a tool designed to systematically assess and track suicidal AEs (suicidal behavior and suicidal ideation) and will be used for all visits.
Participants in the series of ampreloxetine trials are being recruited in two pathways. The first is SEQUOIA followed by REDWOOD and finishing with OAK. The second is REDWOOD followed byOAK. There will, of course, be dropouts along the way. The inclusion criteria require subjects over the age of 30, diagnosed with nOH and one of PD, MSA or PAF. These criteria are also used to assess de novo entrants to REDWOOD. Exclusion criteria prevent the use of any monoamine oxidase inhibitor (MAOI), which is notable given that MAOI-B inhibitors are very commonly used in PD. Participants in OAK can only come from the REDWOOD trial and must continue to meet the latter’s inclusion criteria. The slightly unusual design of REDWOOD is intended to measure the durability of action of ampreloxetine. Participants are established on active dose for 16 weeks, prior to the six-week blinded phase to assess ampreloxetine against placebo. All of the outcome measures are focused on this phase. Given the scale of the problem with nOH in PD, with a reduced quality of life, and the potential for serious injury from falls, we look forward to the release of data from the SEQUOIA trial shortly after the projected completion date of August 2021.