Third, I thought the inhaled antibiotics were continued throughout the phase 2 VX-809/Kalydeco trial. There was a presentation by Michael Boyle, MD with a slide showing baseline characteristics for the phase 2 study participants. The 600 mg VX-809/Kalydeco group had 86% on inhaled antibiotics and the placebo group had 91% on inhaled antibiotics. Stopping the inhaled antibiotics at any point during the study would add a confounding variable. The phase 3 Ataluren study showed it was more difficult to show improvement when patients are using inhaled antibiotics. Therefore the 6.7% improvement seen with those receiving the combo compared to placebo is more impressive if most of the patients were using inhaled antibiotics.
What I remember from the early May conf call is that the trial participants were on antibiotics during the monotherapy phase but off of it during the combo phase of the trial. CFers on antibiotics take it for a month and don't take it for a month. So, it was possible to synchronize the drug dosing to the antibiotic cycle. I don't remember who was saying at the cc, but he [speculated] that the reason the FEV1 of the placebo arm went down so much during the 2nd half of the trial was because the participants were off the antibiotics during the period.
In the coming Phase III trial the trial period would be 6 month or so, several antibiotics cycles can be put in, and the effects of taking antibiotics would be apparent both for the placebo and drug arms.
I would think that removal of antibiotics would certainly increase pulmonary distress, and ensueing respiratory distress such as pulmonary exacerbation or dispnea would depress FEV1. This can happen in both placebo and treatment arms. If antibiotics were given to the 200mg and 400mg arms, the FEV1 would be higher. But for the 600 mg arm the effects of antibiotics would be less because the drugs by themselves clear infection and inflammation.