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Trial record 1 of 1 for:    NCT03191864 | Eosinophilic Esophagitis | United States
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Efficacy, Safety, and Pharmacokinetics of APT-1011 in Subjects With Eosinophilic Esophagitis (EoE) (FLUTE)

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ClinicalTrials.gov Identifier: NCT03191864
Recruitment Status : Active, not recruiting
First Posted : June 19, 2017
Last Update Posted : December 13, 2018
Sponsor:
Information provided by (Responsible Party):
Adare Pharmaceuticals, Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Drug: APT-1011 Drug: Placebo Phase 2

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, 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double Blind
Primary Purpose: Treatment
Official Title: FLUTicasone in Eosinophilic Esophagitis (FLUTE): A Randomized, Double-blind, Placebo-controlled, Dose-ranging, and Maintenance Study of APT-1011 in Subjects With Eosinophilic Esophagitis
Actual Study Start Date : June 30, 2017
Estimated Primary Completion Date : January 30, 2019
Estimated Study Completion Date : August 30, 2019


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 Name: Fluticasone propionate ODT

Drug: Placebo
Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.
Other Name: 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 Name: 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 Name: Fluticasone propionate ODT

Drug: Placebo
Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.
Other Name: 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 Name: 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 Name: Matching placebo dose




Primary Outcome Measures :
  1. Histological response [ Time Frame: Week 12 ]
    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).


Secondary Outcome Measures :
  1. EoE sustained response [ Time Frame: Week 12, Week 26, and Week 52 ]
    Percentage of subjects who met the primary endpoint (histology) at Week 12 and maintained the primary endpoint at Week 26 and Week 52

  2. Change from baseline EREFs at Week 12, 26, and 52 [ Time Frame: Week 12, Week 26, and Week 52 ]
    Endoscopic changes will be assessed as per the EREFs evaluation based on the following endoscopic features: edema, rings, exudates, furrows, stricture, and several miscellaneous features (crepe paper esophagus, narrow caliber esophagus, and esophageal erosions).

  3. EoE histologic response [ Time Frame: Week 12, Week 26, and Week 52 ]
    Percentage of subjects with a peak eosinophils/HPF <1 and <15 at Week 12, 26 and 52.

  4. Change from baseline Global EoE Symptom Score [ Time Frame: Week 52 ]
    Compared score prior to randomization to scores for 7-day recall at Week 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52 visits

  5. Dysphagia [ Time Frame: Week 12, Week 26 and Week 52 ]
    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


Other Outcome Measures:
  1. HPA axis suppression [ Time Frame: baseline to Week 52 ]
    Number of subjects discontinuing due to HPA axis suppression

  2. Candidiasis [ Time Frame: baseline to Week 52 ]
    Frequency of oral and esophageal candidiasis

  3. Oral clearance [ Time Frame: Week 12 ]
    Oral clearance (CL/F)

  4. Volume of distribution [ Time Frame: Week 12 ]
    Volume of distribution (V/F)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03191864


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

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Responsible Party: Adare Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03191864     History of Changes
Other Study ID Numbers: SP-1011-002
2016-004749-10 ( EudraCT Number )
First Posted: June 19, 2017    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adare Pharmaceuticals, Inc.:
Esophagitis
Eosinophilic Esophagitis
Fluticasone
Dysphagia
Safety
Efficacy
Pharmacokinetics
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Glucocorticoids
Orally Disintegrating Tablet
Additional relevant MeSH terms:
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Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents