Efficacy, Safety, and Pharmacokinetics of APT-1011 in Subjects With Eosinophilic Esophagitis (EoE) (FLUTE)

FLUTicasone in Eosinophilic Esophagitis (FLUTE): A Randomized, Double-blind, Placebo-controlled, Dose-ranging, and Maintenance Study of APT-1011 in Subjects With Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, characterized by eosinophilic infiltration and gastrointestinal symptoms. Swallowed, topically acting corticosteroids, such as fluticasone, appear to be effective in resolving acute clinical and pathological features of EoE.

APT-1011 is an orally disintegrating tablet (ODT) formulation of fluticasone propionate. This study is designed to compare the efficacy and safety of APT-1011 with placebo in adults with EoE for an initial 12-week treatment period, followed by an additional 40-week maintenance treatment phase. Histologic response, pharmacokinetics, and dysphagia will be assessed.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Drug: APT-1011; Drug: Placebo

Detailed Description

FLUTE is a phase 2b randomized, double-blind, placebo-controlled dose-ranging clinical trial of APT-1011 versus placebo in 100 adult subjects (≥18 years of age) diagnosed with EoE. Efficacy (including histologic, endoscopic, and symptomatic response), safety, and PK of APT-1011 will be examined. Participants will be given an electronic diary to record symptoms and medication intake daily.

FLUTE will be conducted in several parts (Screening [4 weeks], followed by a 4-week Baseline Symptom Assessment, and 2 treatment parts [Part 1: 14-week Induction and Part 2: 38-week Maintenance]), with a follow-up visit to occur 2 weeks after the final dose of study drug.

In Part 1 of the study, approximately 100 subjects will be randomized 1:1:1:1:1 to receive placebo or one of 4 active doses of APT-1011. All subjects will receive one tablet 30 minutes after breakfast and one tablet at bedtime (HS). The dosing groups include: 1.5 mg HS APT-1011, 1.5 mg twice daily (BID) (total daily dose of 3 mg) APT-1011, 3 mg HS APT-1011, and 3 mg BID (total daily dose of 6 mg) APT-1011, and placebo BID.

In Part 2, all subjects classified as histologic responders at Week 12 will continue to be treated according to the dosing group to which they were randomized, and non-responders will receive single-blind 3 mg BID. All subjects who are histologic non-responders at Week 26 will stop treatment at Week 28 and enter the 2-week follow-up and exit the study. Histologic responders at Week 26 will continue on the same dose until end-of-study at Week 52.

Subjects will complete a follow-up visit 2 weeks after the final dose of study drug. All subjects must have a final EGD within 3 weeks prior to completing the Follow-up Visit unless the subject withdraws consent or has a contraindication to EGD.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8310
    • AZ Sint-Lucas
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Kortrijk, Belgium, 8500
    • AZ Groeninge - Kennedylaan
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • (G.I.R.I.) GI Research Institute
  • Nova Scotia
    • Bridgewater, Nova Scotia, Canada, B4V 3N2
      • Viable Clinical Research
  • Ontario
    • Lindsay, Ontario, Canada, K9V 5G6
      • Viable Clinical Research
    • London, Ontario, Canada, N6A 5A5
      • London Health Science Centre
    • Oshawa, Ontario, Canada, L1H 7K4
      • Taunton Surgical Centre
• Germany
  • Bayern
    • Muenchen, Bayern, Germany, 81675
      • Klinikum rechts der Isar der TU Muenchen
  • Brandenburg
    • Brandenburg an der Havel, Brandenburg, Germany, 14770
      • Staedisches Klinikum Brandenburg
  • Nordrhein Westfalen
    • Muenster, Nordrhein Westfalen, Germany, 48159
      • Praxis am Germania
  • Sachsen
    • Leipzig, Sachsen, Germany, 4103
      • Universitaetsklinikum Leipzig AoeR
  • Schleswig Holstein
    • Kiel, Schleswig Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein
• Spain
  • Alicante, Spain, 3010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu I Sant Pau
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Ciudad Real
    • Tomelloso, Ciudad Real, Spain, 13700
      • Hospital General de Tomelloso
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Del Sol Research Management, LLC
    • Tucson, Arizona, United States, 85710
      • Del Sol Research Management, LLC
  • Arkansas
    • Sherwood, Arkansas, United States, 72120
      • Arkansas Gastroenterology, P.A.
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • El Cajon, California, United States, 92020-4124
      • TriWest Research Associates, LLC
    • Garden Grove, California, United States, 92844
      • SC Clinical Research, Inc.
    • Los Angeles, California, United States, 90048
      • Beverly Hills Center for Digestive Health
    • Oxnard, California, United States, 93030
      • FocilMed
    • San Diego, California, United States, 92123
      • Medical Associates Research Group, Inc.
    • San Diego, California, United States, 92114
      • Precision Research Institute, LLC
    • San Pablo, California, United States, 94806
      • Care Access Research LLC
    • Stanford, California, United States, 94305-2200
      • Stanford University School of Medicine
    • Yorba Linda, California, United States, 92886
      • St. Jude Healthcare
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Western Connecticut Health Network
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Hialeah, Florida, United States, 33013
      • Eastern Research, Inc.
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research, LLC
    • Lauderdale Lakes, Florida, United States, 33319
      • Sunrise Medical Research
    • Pembroke Pines, Florida, United States, 33029
      • DBC Research, Corp
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Faculty Foundation
    • Oak Lawn, Illinois, United States, 60453-3767
      • Southwest Gastroenterology
    • Rockford, Illinois, United States, 61107
      • Rockford Gastroenterology Associates, Ltd.
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, an AMR affiliate
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center, Digestive Health
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Gastroenterology Associates
  • Louisiana
    • West Monroe, Louisiana, United States, 71291
      • Clinical Trials of America, Inc.
  • Michigan
    • Novi, Michigan, United States, 48377-3600
      • Henry Ford Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • St. Louis Center for Clinical Research
  • New York
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group, LLP
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
    • Mooresville, North Carolina, United States, 28117
      • Research Institute of the Carolinas, PLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27607
      • Carolina's GI Research, LLC
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center, LLC
    • Columbus, Ohio, United States, 43231
      • Aventiv Research Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • Unity Clinical Research
  • Oregon
    • Medford, Oregon, United States, 97504
      • Allergy and Asthma Center of South Oregon
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Digestive Disease Associates, Ltd.
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center, LLP
  • Tennessee
    • Union City, Tennessee, United States, 38261
      • Advanced Gastroenterology
  • Texas
    • Austin, Texas, United States, 78704
      • Avant Research Associates, LLC - Austin
    • Beaumont, Texas, United States, 77702
      • Avant Research Associates, LLC
    • Richardson, Texas, United States, 75082
      • DHAT Research Institute
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
    • Salt Lake City, Utah, United States, 84124
      • Care Access Research LLC
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Verity Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female between ≥18 and ≤75 years of age at the time of informed consent
• Signed informed consent
• Evidence of EoE defined by ≥15 peak eosinophils per HPF as measured from proximal and distal biopsies
• Subject-reported history of ≥3 episodes of dysphagia in the 7 days prior to Screening
• 7-day Global EoE Symptom Score >3 at baseline and at screening
• Willing and able to adhere to study-related treatment regimens, procedures, and visit schedule

Exclusion Criteria:

• Have known contraindication, hypersensitivity, or intolerance to corticosteroids;
• Have any physical, mental, or social condition or history of illness or laboratory abnormality that in the Investigator's judgment might interfere with study procedures or the ability of the subject to adhere to and complete the study;
• Presence of oral or esophageal mucosal infection of any type;
• Have any mouth or dental condition that prevents normal eating;
• Have any condition affecting the esophageal mucosa or altering esophageal motility other than EoE;
• Use of systemic corticosteroids within 60 days prior to Screening, use of inhaled/swallowed corticosteroids within 30 days prior to Screening, or extended use of high-potency dermal topical corticosteroids within 30 days prior to Screening;
• Initiation of an elimination diet or elemental diet within 30 days before Screening (diet must remain stable after signing ICF);
• Morning serum cortisol level ≤5 μg/dL (138 nmol/L);
• Use of biologic immunomodulators in the 24 weeks prior to Screening;
• Use of calcineurin inhibitors or purine analogues, or potent cytochrome P450 (CYP) 3A4 inhibitors in the 12 weeks prior to Screening;
• Have a contraindication to or factors that substantially increase the risk of EGD or esophageal biopsy or have narrowing of the esophagus that precludes EGD with a standard 9 mm endoscope;
• Have a history of an esophageal stricture requiring dilatation within the previous 12 weeks prior to Screening;
• Have initiated, discontinued or changed dosage regimen of PPIs, H2 antagonists, antacids or antihistamines for any condition such as GERD or allergic rhinitis within 4 weeks prior to qualifying endoscopy. These drugs must remain constant throughout the study.
• A serum cortisol level <18 μg/dL (497 nmol/L) at 60 minutes with adrenocorticotropic hormone (ACTH) stimulation test using 250 μg cosyntropin (i.e., a positive result on the ACTH stimulation test).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APT-1011 1.5 mg HS; Placebo after breakfast, APT-1011 1.5 mg HS	Drug: APT-1011; APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate; Other Names: Fluticasone propionate ODT; Drug: Placebo; Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.; Other Names: Matching placebo dose
Experimental: APT-1011 1.5 mg BID; APT-1011 1.5 mg after breakfast, APT-1011 1.5 mg HS	Drug: APT-1011; APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate; Other Names: Fluticasone propionate ODT
Experimental: APT-1011 3 mg HS; Placebo after breakfast, APT-1011 3 mg HS	Drug: APT-1011; APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate; Other Names: Fluticasone propionate ODT; Drug: Placebo; Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.; Other Names: Matching placebo dose
Experimental: APT-1011 3 mg BID; APT-1011 3 mg after breakfast, APT-1011 3 mg HS	Drug: APT-1011; APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate; Other Names: Fluticasone propionate ODT
Placebo Comparator: Placebo BID; Placebo 30 minutes after breakfast and HS	Drug: Placebo; Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.; Other Names: Matching placebo dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With ≤6 Peak Eosinophils/High-power Field (HPF)	Histology (eosinophils per high power field [HPF]): percentage of subjects with ≤6 PEAK eosinophils/HPF after assessing at least 5-6 biopsies from the proximal and distal esophagus (~3 each) where the HPF area is 235 square microns (40 magnification lens with a 22 mm ocular).	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Met the Primary Endpoint at Week 12 and Maintained the Primary Endpoint at Weeks 26 and 52	Percentage of subjects who entered Part 2 - Maintenance and met the primary endpoint (histology) at Week 12 and maintained the primary endpoint at Week 26 and Week 52. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect percentage of subjects who met the primary endpoint following 12 or 38 weeks of treatment.	Week 26, and Week 52
Change From Baseline Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) at Week 12, 26, and 52	Endoscopic changes will be assessed as per the EREFs evaluation based on the following endoscopic features: edema [Grade {Gr} 0 (absent) or Gr 1 (present)], strictures [Gr 0 (absent) or Gr 1 (present)], rings [Gr 0 (none), Gr 1 (mild), Gr 2 (moderate), Gr 3 (severe)], exudates [Gr 0 (none), Gr 1 (mild), Gr (severe)], furrows [Gr 0 (none), Gr 1 (mild), Gr 2 (severe)], crepe paper esophagus [Gr 0 (absent) or Gr 1 (present)], narrow caliber esophagus [Gr 0 (absent) or Gr 1 (present)], and esophageal erosions [Normal (0), Gr A (1), Gr B (2), Gr C (3), or Gr D (4)]. EREFs: 0 (best) to 15 (worst) based on the sum of the subscores listed above. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3 mg BID and results reflect EREF evaluation following 12 or 38 weeks of treatment.	Week 12, Week 26, and Week 52
Percentage of Subjects With a Peak Eosinophils/HPF Number <1 and <15	Percentage of subjects with a peak eosinophils/HPF <1 and <15 at Week 12, 26 and 52. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect peak eosinophils/HPF following 12 or 38 weeks of treatment.	Week 12, Week 26, and Week 52
Change From Baseline Global EoE Symptom Score	Change from baseline global EOE symptom score assessed prior to randomization to scores for 7-day recall at Week 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52 visits. Global Eosinophilic Esophagitis Symptom Score: On a scale from 0 (no symptoms) to 10 (most severe symptoms), how severe were your EoE symptoms over the past 7 days? Patients were asked to think of all their symptoms due to EoE and make an overall statement by selecting a number. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline global EOE symptom score following 4, 8, 12, 14, 22, 30 or 38 weeks of treatment.	Week 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52
Change in the Number of Dysphagia Episodes	Change in the number of dysphagia episodes at baseline (14-day period prior to randomization) compared with the 14-day period prior to the time point of interest. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect the change in the number of dysphagia episodes following 12 or 38 weeks of treatment.	Week 12, Week 26 and Week 52
Change From Baseline 7-Day Eosinophilic Esophagitis Activity Index (EEsAI) Total Score	Change from Baseline 7-Day EEsAI total score assessed prior to randomization and those assessed at Weeks 12, 26 and 52 (Total score 100). Eosinophilic Esophagitis Activity Index Total Score: 0 (best) to 100 (worst) based on the sum of the categorized subscores for frequency of trouble swallowing [never (0), 1-3x (15) or 4-6x (27) per week]; duration of trouble swallowing [≤5 min (0), >5 min (6)]; pain when swallowing [no (0), yes (15)]; Visual Dysphagia Question score [0 (best),12,19, 21, or 23 (worst)]; avoidance modification and slow eating score [0 (best), 9, or 25 (worst)]. A higher score means a worse outcome. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect the change from baseline 7-day EEs	Weeks 12, 26 and 52
Change From Baseline 7-Day Eosinophilic Esophagitis Activity Index (EEsAI) Subscores	The Avoidance, Modification and Slow Eating (AMS) Score and Visual Dysphagia Question (VDQ) Score are components of the EEsAI. AMS: Answers to three items determining the pattern of behavioral adaptation were scored for each food consistency consumed by the subject (avoidance, modification, and eating slowly). The AMS score ranges from 0 (best) to 25 (worst). VDG: The degree of perceived difficulty when eating 8 different food consistencies was assessed. The VDQ score ranges from 0 (best) to 23 (worst). A higher score for either subscore means a worse outcome. Negative change from baseline represents a worsening in quality of life for the total score or subscore. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline.	Weeks 12, 26 and 52
Percentage of Subjects With Mean 7-day EEsAI Total Score <20	Percentage of subjects with mean 7-day EEsAI total score <20 to those assessed at Weeks 12, 26 and 52. Eosinophilic Esophagitis Activity Index Total Score: 0 (best) to 100 (worst) based on the sum of the categorized subscores for frequency of trouble swallowing [never (0), 1-3x (15) or 4-6x (27) per week]; duration of trouble swallowing [<= 5 min (0), >5 min (6)]; pain when swallowing [no (0), yes (15)]; Visual Dysphagia Question score [0 (best),12,19,21, or 23 (worst)]; avoidance modification and slow eating score [0 (best), 9, or 25 (worst)]. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline global EOE symptom score following 12 or 38 weeks of treatment	Weeks 12, 26, and 52
Change From Baseline Patient Global Impression of Severity (PGIS) for EoE Symptoms as Assessed Prior to Randomization Post-Baseline Visit	Change From Baseline PGIS for EoE Symptoms as Assessed Prior to Randomization at Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline global EOE symptoms following 4, 8, 12, 14, 22, 30 or 38 weeks of treatment.	Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52
Change From Baseline PGIS for Difficulty With Food or Pills Going Down as Assessed Prior to Randomization Post-Baseline Visit	Change From Baseline PGIS for Difficulty with Food or Pills Going Down as Assessed Prior to Randomization at Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline PGIS for difficulty with food or pills going down following 4, 8, 12, 14, 22, 30 or 38 weeks of treatment.	Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52
Change From Baseline Patient Global Impression of Change (PGIC) for EoE Symptoms as Assessed Prior to Randomization Post-Baseline Visit	Change From Baseline PGIC for EoE Symptoms as Assessed Prior to Randomization at Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline PGIC for EoE symptoms following 4, 8, 12, 14, 22, 30 or 38 weeks of treatment.	Weeks 4, 8, 12, 14, 18, 22, 26, 36, 44, and 52
Change From Baseline PGIC of Difficulty With Food or Pills as Assessed Prior to Randomization Post-Baseline Visit	Change From Baseline PGIC of Difficulty with Food or Pills as Assessed Prior to Randomization at Weeks 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52. Population used are those who entered Part 1 - Induction. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect change from baseline PGIC of difficulty with food or pills following 4, 8, 12, 14, 22, 30 or 38 weeks of treatment.	Weeks 4, 8, 12, 14, 18, 22, 26, 36, 44, and 52
Percentage of Histologic Non-responders by Dose at Weeks 12, 26, and 52	Percentage of histologic non-responders by dose at Weeks 12, 26, and 52. Note: Following Week 14, all patients in the placebo group were given APT-1011 3mg BID and results reflect non-response following 12 or 38 weeks of treatment.	Weeks 12, 26 and 52
Percentage of Subjects Requiring Emergency Endoscopic Food Dis-impaction	Percentage of subjects requiring emergency endoscopic food dis-impaction by dose before Week 14, between Week 14 and Week 28, and between Week 28 and Week 52. Note: There were no patients in the placebo group after Week 14.	before Week 14, between Week 14 and Week 28, between Week 28 and Week 52
Percentage of Subjects Requiring Esophageal Dilation	Percentage of subjects requiring esophageal dilation by dosing group and part of the study. Note: There were no patients in the placebo group after Week 14.	baseline to Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Discontinuing Due to HPA Axis Suppression	Number of subjects discontinuing due to HPA axis suppression. Note: There were no patients in the placebo group after Week 14.	baseline to Week 52
Number of Subjects With Oral and Esophageal Candidiasis	Frequency of oral and esophageal candidiasis. Note: There were no patients in the placebo group after Week 14.	baseline to Week 52
Number of Subjects With Treatment-Emergent Adverse Events Leading to Study Discontinuation in Part 1	Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Discontinuation in Part 1.	baseline to Week 12
Number of Subjects With Treatment-Emergent Adverse Events Leading to Study Discontinuation in Part 2	Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Discontinuation in Part 2.	Week 12 to 52
Percentage of Subjects With Serum Cortisol Level ≤5 μg/dL or Abnormal Adrenocorticotropic Hormone (ACTH) Stimulation Test	Percentage of subjects with serum cortisol level ≤5 μg/dL (≤138 nmol/L) or abnormal adrenocorticotropic hormone (ACTH) stimulation test (serum cortisol <16 μg/dL [≤440 nmol/L] at 60 minutes). Population used are those who entered Part 2 - Maintenance. The number of participants analyzed for each timepoint reflect the actual number of participants with data at that timepoint.	Week 12 to 52

Collaborators and Investigators

• Sponsor: Adare Pharmaceuticals, Inc.
• Investigators: Study Director: Peter C Richardson, Adare Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Dellon ES, Lucendo AJ, Schlag C, Schoepfer AM, Falk GW, Eagle G, Nezamis J, Comer GM, Knoop K, Hirano I. Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2485-2494.e15. doi: 10.1016/j.cgh.2022.02.013. Epub 2022 Feb 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Actual): January 3, 2019
• Study Completion (Actual): October 23, 2019

Study Registration Dates

• First Submitted: June 15, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Dysphagia; Pharmacokinetics; Gastrointestinal Diseases; Digestive System Diseases; Esophagitis; Glucocorticoids; Eosinophilic Esophagitis; Esophageal Diseases; Fluticasone; Orally Disintegrating Tablet
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: SP-1011-002; 2016-004749-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No