Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis

This will be a prospective, randomized, double-blind, double-dummy, clinical trial comparing
oral viscous budesonide (OVB) to fluticasone metered dose inhaler (MDI) for treatment of EoE.
A total of 122 subjects aged 16-80 years old will be randomized in a 1:1 fashion to one of
two active treatment arms: OVB + placebo inhaler or fluticasone MDI + placebo slurry.

In the first arm, subjects will be treated with OVB at a dose of 1 mg twice daily, and they
will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with
instructions to swallow 4 puffs twice daily. The OVB is a slurry equivalent to what is used
clinically: 1 mg/4 mL aqueous budesonide mixed with 10 g of sucralose. Rather than asking the
subjects to mix the slurry on their own and risk inconsistent formulations, the UNC
investigational drug pharmacy (IDP) will provide pre-mixed OVB to all patients. The IDP will
also provide placebo inhalers to all patients. The dose for OVB has been chosen because it is
the most commonly studied dose, including one prior study led by this Principal Investigator,
so we can accurately estimate response rates.

In the second arm, subjects will be treated with fluticasone MDI at a dose of 880 mcg twice
daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4
mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the
OVB. The UNC investigational drug pharmacy (IDP) will provide the fluticasone MDIs and
pre-mixed placebo slurries to all patients. The dose for fluticasone MDI has been chosen
because this is the most commonly used dose in adolescents and adults with EoE, so effect
estimates are also available.

For both arms, the slurry will be administered first, the MDI will be administered 15 minutes
later, and patients will take nothing by mouth for an additional 30 minutes.

Subjects will receive 8 weeks of treatment and will then be monitored for up to 52 weeks for
recurrence of symptoms.

Inclusion criteria are as follows:

- Age: 16 - 80 years

- Subject is having a clinically indicated endoscopy for suspicious EoE and has been on
BID PPI for at least 8 weeks OR New diagnosis of EoE as per consensus guidelines.
Cases must have symptoms of dysphagia, persistent esophageal eosinophilia (≥ 15
eosinophils in at least one high-power field) after 8 weeks of treatment with a twice
daily proton-pump inhibitor, and other competing causes of esophageal eosinophilia
excluded.

Exclusion criteria are as follows:

- Medical instability that precludes safely performing upper endoscopy

- Ongoing or recent symptoms of intestinal bleeding (throwing up blood, passing blood in
the stool)

- Concomitant eosinophilic gastroenteritis

- Esophageal narrowing or stricturing that will not allow a standard 9 mm upper
endoscopy scope to pass

- Cancer in the esophagus, stomach, or intestine

- Previous esophageal surgery

- Esophageal varices (dilated blood vessels in the esophagus)

- Current use of blood thinners like Plavix or Coumadin that are not stopped prior to
endoscopy procedures

- Any corticosteroid exposure within the 4 weeks prior to their baseline endoscopic
exam. Exclusionary corticosteroid exposure is defined as any swallowed topical
steroids for EoE or systemic steroids for any condition within the four weeks prior to
the baseline endoscopy. Corticosteroids used for asthma or intranasal corticosteroids
are not an exclusion and are allowable.

- Pregnancy

- Inability to read or understand English