Tolerability of Inhaled Hypertonic Saline in Infants With Cystic Fibrosis

The efficacy and safety of hypertonic saline (HS) in CF patients over 6 years of age has been
demonstrated in clinical trials of 2 to 48 weeks' duration. Based on these results, a large
randomized, placebo-controlled trial of the efficacy and safety of 7% HS administered twice
daily for 48 weeks to infants with CF, 4 to 15 months of age at enrollment, is planned (the
Infant Study of Inhaled Saline (ISIS) trial). It is anticipated that 150 infants at up to 16
sites will be enrolled in the ISIS trial.

To date, the only evaluations of the safety of HS in infants with CF have been small
single-dose studies. There has been no evaluation of the tolerability of chronic HS
administration. The goal of this study is to assess the safety and tolerability of exposure
to 14 days of 7% HS administered twice daily in infants with CF, prior to enrolling subjects
in the planned large, randomized, controlled trial. Conduct of this study will provide
evidence for the tolerability of chronic HS administration in infants with CF and estimates
of the proportion of infants who do not tolerate chronic HS treatment. The results will be
used to establish the appropriate measures of tolerability at enrollment in the ISIS trial,
and to refine sample size estimates to account for withdrawal due to intolerance of HS.

Inclusion Criteria:

- Diagnosis of CF as defined by one or more clinical features of CF and a documented
sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype
showing two well characterized disease causing mutations

- Informed consent by parent or legal guardian

- 12-30 months of age at enrollment

Exclusion Criteria:

- Wheezing at the baseline evaluation at the enrollment visit

- Oxygen saturation < 95 % at the baseline evaluation at the enrollment visit

- Acute intercurrent respiratory infection, defined as an increase in cough, wheezing,
or respiratory rate, or new rhinorrhea, nasal congestion or rhinorrhea, with onset in
the week preceding the enrollment visit

- Investigational drug use within 30 days prior to the enrollment visit

- Known intolerance of albuterol

- Current enrollment in a therapeutic clinical trial

- Condition or situation which, in the opinion of the investigator, would affect the
ability of the patient or family to complete study procedures