Tolerability of Inhaled Hypertonic Saline in Infants With Cystic Fibrosis (ISIS Pilot)

• New or increased cough, increased qualitative breathing rate, new or increased noisy breathing, or new or increased emesis at home as noted by parents on the daily symptom report [ Time Frame: During the period of home administration (Days 0 to 14) ] [ Designated as safety issue: Yes ]
• Change in respiratory rate, oxygen saturation, or cough frequency between the baseline measurement and measurements obtained after HS administration [ Time Frame: At the enrollment visit ] [ Designated as safety issue: Yes ]
• Change in respiratory rate, oxygen saturation, or cough frequency between the baseline value at the enrollment visit and the value at the final study visit [ Time Frame: Over two weeks of study participation ] [ Designated as safety issue: Yes ]
• Unanticipated adverse events [ Time Frame: Over two weeks of study participation ] [ Designated as safety issue: Yes ]
• Adherence, as measured by (1) the number of doses of HS administered per the home symptom report and (2) returned study drug vials [ Time Frame: During the period of home administration (Days 0 to 14) ] [ Designated as safety issue: No ]

• New or increased cough, increased qualitative breathing rate, new or increased noisy breathing, or new or increased emesis at home as noted by parents on the daily symptom report [ Time Frame: During the period of home administration (Days 0 to 14) ]
• Change in respiratory rate, oxygen saturation, or cough frequency between the baseline measurement and measurements obtained after HS administration [ Time Frame: At the enrollment visit ]
• Change in respiratory rate, oxygen saturation, or cough frequency between the baseline value at the enrollment visit and the value at the final study visit [ Time Frame: Over two weeks of study participation ]
• Unanticipated adverse events [ Time Frame: Over two weeks of study participation ]
• Adherence, as measured by (1) the number of doses of HS administered per the home symptom report and (2) returned study drug vials [ Time Frame: During the period of home administration (Days 0 to 14) ]

This is an open-label pilot study of the safety and tolerability of 7% hypertonic saline inhaled twice daily for 14 days in infants with CF, 12 to 30 months of age.

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