From the description of the Arikace follow-on long term safety study -
[Eligible subjects will receive 560 mg Arikace™ once daily via a PARI Investigational eFlow® Nebulizer for 28 days followed by a 28 day off treatment period. This cycle (28 days on-treatment, 28 days off-treatment) will be repeated for up to twelve cycles. The study will be implemented as two consecutive extension periods, each consisting of 48 weeks ...
During the first 28 days of treatment, subjects will be evaluated at the clinic bi-weekly for safety, tolerability and efficacy. Thereafter, for the duration of the study, subjects will be evaluated at the clinic on the first and last days of dosing during the on-treatment periods. A final site visit will occur 28 days after last dose of Arikace™.]
The participants who became eligible for the safety study, by virtue of their participation in the EU Phase III clinical trial from which results are expected mid-year, will have known whether they were taking Arikace or the comparator drug Tobi.
The two nebulisation-inhalation systems are not at all similar - and it's likely that an individual with a history of chronic infection with Pseudomonas aeruginosa would previously have used Tobi.
If the participants who were taking Arikace were impressed, one would imagine that throughout the course of the study word will have been filtering across to the participants on Tobi, and that a high proportion of both the approx 150 on Tobi and the approx 150 on Arikace will have volunteered for the safety study.
If Arikace has been less than impressive, one would imagine that a large proportion of the approx 300 participants will have declined the follow-on study (and the associated visits to the clinic for tests) in favour of resuming their previous routines.
From the Seeking Alpha transcript of the May 7 call -
[Joseph Schwartz - Leerink Swann
Good morning. I was wondering if you could give us any more insight into the proportion of patients that you see transitioning from the randomized control portion of CLEAR-108 into the extension study.
Yes. Good morning, Joe. Thanks for the question. Actually, this is going to be one of those frustrating calls this morning because we have data that is just around the corner. We just are not going to be in the position to disclose it until it's finalized.
With respect to this particular issue of carryover, while we had last patient, last visit yesterday, we would like to see the final definitive number so we can just come out and state it. And I anticipate that we would do that in the not-too-distant future by way of some form of disclosure, perhaps at the UBS Conference, if we know it by then.]
The UBS conference was last week. I didn't listen in, but I'm sure the carryover figure would have been posted here had Lewis disclosed it.
PR next week?
Why four thumbs-down ratings for this? -
The most important factor in all of this I suspect has been widely overlooked is that the study which has just been completed is the first Arikace multi-cycle study where the therapy has been interrupted by breaks of only four weeks.
Can we rule out the possibility that the results from this study will be far more impressive than the impressive Phase II results?
From WL at the May 20 investor presentation at the 11:52 time mark:
"We are very excited about the carry over rate from patients on the treatment portion of the study into the open label study because we think that suggests that not only in the clinical setting is the drug useful to them, but they are interested in continuing treatment for the long term even though there is a heavy burden in staying in these studies as you are all aware."
This statement seems to indicate that WL knows the carry over rate and he thinks it is very good. However, I suppose this statement could be interpreted as WL being exciting about the prospect of seeing the actual carry over rate.
If you check clinicaltrials.gov, the estimated enrollment for the extension study is 250. So they must be expecting a sizeable cohort of the Tobi group to switch over to Arikace. It will be interesting to see what this data in the switchover group will show. It could be the final nail in the coffin for Tobi if they show a marked improvement in the primary and secondary outcome measures.