Original Source: FD (FAIR DISCLOSURE) WIRE
ROLAND HAEFELI, IR, ACTELION LTD.: Good morning, ladies and gentlemen. Welcome to the Actelion conference call. Today we have announced that the proof-of-concept study in patients with primary insomnia receiving Actelion's Orexin-OX1/OX2 receptor antagonist ACT-078573 has met its primary endpoint, an improvement in sleep efficiency measured by Polysomnography. To discuss this important finding -- because indeed now, for the first time, we do know that orexin place a key role in human sleep architecture -- I would like to hand over to Isaac Kobrin to discuss with you what we have obtained so far in the study, who -- and this is very important -- this study is ongoing now in a dose-finding fashion. Isaac, your time.
ISAAC KOBRIN, HEAD OF CLINICAL DEVELOPMENT, ACTELION LTD.: Thank you, Roland. This was a multicenter, multistage, double-blind, randomized, placebo-controlled, two-way crossover single-dose study. The objective was to investigate the effect of this orexin receptor antagonist on sleep, measured by Polysomnography, in patients with primary insomnia. This is the first study in patients with primary insomnia after seeing signs of effect in healthy volunteers in our previous study that we already informed you about.
On the next page, we can see the design of the study. It is a multistage design, which is quite unique. The way it was done is as follows. We chose the initial dose based on the healthy volunteer study, based on the observation of the healthy volunteer study. If this initial dose meets its primary parameter, then we go to the next lower dose. If it doesn't meet the primary parameter, then you go to a higher dose. So we chose a dose that seemed to work in healthy volunteers; and from this, we were able to go either down or up. So this was the design.
The first stage of this study was the proof-of-concept aspect. Once you meet this proof-of-concept, then comes the part of the dose-finding and finding the minimal effective dose by going from dose to dose down.
The next stage, you can see that the primary parameter was sleep efficiency as assessed by Polysomnography. What is sleep efficiency? It is a total sleep time divided by total time in bed. The total time in bed was fixed for 8 hours. The Polysomnography recording started when the patient went into bed between 10 and 12 at night.
On the next slide, you can see some of the secondary and exploratory endpoints. Latency to persistent sleep assessed by Polysomnography. Waking after sleep onset, also measured by PSG. Subjective sleep measurements as reported by the patients. And of course, sleep architecture, the proportion of different sleep stages as assessed by Polysomnography; and this included also REM sleep.
In the next slide you can see the methodology -- per-protocol analysis of primary endpoint after each dose, by independent study station, on the primary endpoint as I explained on the design. The (indiscernible) that should have been met was either this primary endpoint is met or not met. This determines the initial proof-of-concept and the next stages of the trial.
Of course, we were looking at safety findings, based on blinded analysis of serious adverse events and emerging safety findings. This determined the continuation of the trial.
On the next slide, we can see the initial information or results as we got it from this trial. Well, the primary endpoint of the first dose was met. It was highly significant improvement in sleep efficiency of p ( 0.0001; no report of serious adverse events; and no emerging safety findings. Therefore, the investigators were advised to proceed with the next lower dose.
So what can we say about this study? On the next slide. Clearly orexin's system plays a key role in insomnia patients. Primary insomnia patients sleep significantly longer when receiving ACT-078573, our orexin receptor antagonist. The magnitude of the effect suggests positive impact on both sleep induction and sleep maintenance.
On the next slide, we can see the next steps. Study continues to identify dose range and lowest effective dose, now that we have the proof-of-concept verified based …