Cedric O’Gorman: Okay. Thanks, Andrew. So the first question about monotherapy, yes, we did. We did apply the same analysis to the monotherapy study, and again, in the monotherapy study, had a much higher mean change from baseline for placebo of about 14 points, and drug outperformed placebo by approximately 1 point. So it had a higher placebo problem, but the delta was also a little less than what we saw in the adjunctive, but you’re right. When we looked at verifiable, unverifiable, pre-pandemic, post-pandemic and different splits of the data and sites, we definitely saw the same issues. So we don’t feel that the issues were unique to the adjunctive 302 study, but rather broadly across the RELIANCE program. The decision to pursue adjunctive was a strategic decision really based on the fact that 302 was ongoing with, as you pointed out, 1/3 of patients enrolled.
And by improving that design and starting with a new streamlined adjunctive study and new study, that will be the clearest and quickest path to filing for the indication of adjunctive treatment of MDD with the agency. Now the question as to whether can you know anything from the first 100 subjects? Well, you can’t really because it blinded. What you can work on is, you can look at how your studies did over time. And we spent a little bit of time pointing out the pre-pandemic or after the restrictions were lifted and the impact and how the delta improved. And so we do think that maybe the later part of the 301 study is more reflective of the early part of the first 100 patients that we have in 302. And some other thoughts about sample sizing, gave us confidence to say, well, if we had an original target of about 300 patients, these trials — the opportunity for the drug to separate despite all those challenges would exist.
And so we’ve done a number of modeling exercises and talking to statisticians and talking to the clinical sites. And so yes, we — to answer your question directly, we feel pretty confident that with the amended protocol and with the considerations around target sample size, this study could indeed be positive.
Sergio Traversa: Andrew, also consider that the — if you look at the data from the top down, the major impact on Study 301 was focalized, localized on two sites that enrolled about 40 patients together. These two sites that were not — never been presence in Study 302.
Andrew Tsai: Right, right. Okay. And then one more is just on the 304 study RELIANCE IV. Are there any differences in the study design relative to RELIANCE II, the ongoing one? And does it make sense to start a RELIANCE V, actually?
Cedric O’Gorman: Well, let me start with RELIANCE IV before we talk about RELIANCE V. But with the 304 new study, it will be significantly different in terms of the various scales and assessments that we will — we will be asking the raters and the PIs to administer with the patients. Now there are a couple of standard things that you don’t change like your primary efficacy outcome measure. But again, it’s much easier to start with a blank slate than it is to amend the protocol to kind of remove things. So it will be very similar in terms of 2-arm study, four weeks in duration, primary efficacy outcome, the same, and there will be less exploratory secondary endpoints just so that we can really focus in on the efficacy.
Andrew Tsai: Very helpful. Thank you, guys.
Operator: Our next question is from Jay Olson with Oppenheimer. Please proceed with your question.
