Eosinophilic EsophagitisPhase 2FLUTENCT03191864
Efficacy, Safety, and Pharmacokinetics of APT-1011 in Subjects With Eosinophilic Esophagitis (EoE)
A Phase 2 study testing APT-1011 in people with Eosinophilic Esophagitis, run by Adare Pharmaceuticals, Inc. at 75 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Eosinophilic Esophagitis
- What is being tested?
- APT-1011
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 75 sitesin 6 countries
- Study dates
- 22 Jun 2017to 23 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 14Show fewer
- 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).
Trial locations and contacts
75 sites in 6 countries.
75 sites in 6 countries
United States51 sites
Avant Research Associates, LLC - Austin
Austin, Texas, 78704
Avant Research Associates, LLC
Beaumont, Texas, 77702
Hope Clinical Research
Canoga Park, California, 91303
Del Sol Research Management, LLC
Chandler, Arizona, 85224
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Northwestern Medical Faculty Foundation
Chicago, Illinois, 60611
Bernstein Clinical Research Center, LLC
Cincinnati, Ohio, 45231
Aventiv Research Inc.
Columbus, Ohio, 43231
Western Connecticut Health Network
Danbury, Connecticut, 06810
TriWest Research Associates, LLC
El Cajon, California, 92020-4124
MediSphere Medical Research Center, an AMR affiliate
Evansville, Indiana, 47714
Verity Research Inc
Fairfax, Virginia, 22031
SC Clinical Research, Inc.
Garden Grove, California, 92844
Long Island Gastrointestinal Research Group, LLP
Great Neck, New York, 11023
Medical Research Center of Connecticut, LLC
Hamden, Connecticut, 06518
Gastroenterology Associates
Hazard, Kentucky, 41701
Eastern Research, Inc.
Hialeah, Florida, 33013
Nature Coast Clinical Research, LLC
Inverness, Florida, 34452
Sunrise Medical Research
Lauderdale Lakes, Florida, 33319
Beverly Hills Center for Digestive Health
Los Angeles, California, 90048
Allergy and Asthma Center of South Oregon
Medford, Oregon, 97504
Research Institute of the Carolinas, PLC
Mooresville, North Carolina, 28117
Weill Cornell Medical College
New York, New York, 10021
Henry Ford Medical Center
Novi, Michigan, 48377-3600
Southwest Gastroenterology
Oak Lawn, Illinois, 60453-3767
Advanced Research Institute
Ogden, Utah, 84405
Unity Clinical Research
Oklahoma City, Oklahoma, 73118
Focilmed
Oxnard, California, 93030
DBC Research, Corp
Pembroke Pines, Florida, 33029
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Carolina's GI Research, LLC
Raleigh, North Carolina, 27607
Wake Research Associates, LLC
Raleigh, North Carolina, 27612
Rapid City Medical Center, LLP
Rapid City, South Dakota, 57701
DHAT Research Institute
Richardson, Texas, 75082
Rockford Gastroenterology Associates, Ltd.
Rockford, Illinois, 61107
PMG Research of Salisbury, LLC
Salisbury, North Carolina, 28144
University of Utah
Salt Lake City, Utah, 84108
Care Access Research LLC
Salt Lake City, Utah, 84124
Precision Research Institute, LLC
San Diego, California, 92114
Medical Associates Research Group, Inc.
San Diego, California, 92123
Care Access Research LLC
San Pablo, California, 94806
Arkansas Gastroenterology, P.A.
Sherwood, Arkansas, 72120
St. Louis Center for Clinical Research
St Louis, Missouri, 63128
Stanford University School of Medicine
Stanford, California, 94305-2200
Cotton-O'Neil Clinical Research Center, Digestive Health
Topeka, Kansas, 66606
Del Sol Research Management, LLC
Tucson, Arizona, 85710
Advanced Gastroenterology
Union City, Tennessee, 38261
Clinical Trials of America, Inc.
West Monroe, Louisiana, 71291
Metro Health
Wyoming, Michigan, 49519
Digestive Disease Associates, Ltd.
Wyomissing, Pennsylvania, 19610
St. Jude Healthcare
Yorba Linda, California, 92886
Spain9 sites
Hospital General Universitario de Alicante
Alicante, 3010
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Hospital Universitari Vall d'Hebron
Barcelona
Hospital Universitario de La Princesa
Madrid, 28006
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital General de Tomelloso
Tomelloso, Ciudad Real, 13700
Hospital Clinico Universitario de Valencia
Valencia, 46010
Hospital Clinico Universitario Lozano Blesa
Zaragoza, 50009
Hospital Universitario Miguel Servet
Zaragoza, 50009
Canada5 sites
Viable Clinical Research
Bridgewater, Nova Scotia, B4V 3N2
Viable Clinical Research
Lindsay, Ontario, K9V 5G6
London Health Science Centre
London, Ontario, N6A 5A5
Taunton Surgical Centre
Oshawa, Ontario, L1H 7K4
(G.I.R.I.) GI Research Institute
Vancouver, British Columbia, V6Z 2K5
Germany5 sites
Staedisches Klinikum Brandenburg
Brandenburg an der Havel, Brandenburg, 14770
Universitaetsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein, 24105
Universitaetsklinikum Leipzig AoeR
Leipzig, Saxony, 4103
Klinikum rechts der Isar der TU Muenchen
Munich, Bavaria, 81675
Praxis am Germania
Münster, North Rhine-Westphalia, 48159
Belgium4 sites
AZ Sint-Lucas
Bruges, 8310
Universitair Ziekenhuis Gent
Ghent, 9000
AZ Groeninge - Kennedylaan
Kortrijk, 8500
UZ Leuven
Leuven, 3000
About this study
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
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.
Read the 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.
- Conditions
- Eosinophilic Esophagitis
- Being tested
- APT-1011, Placebo
- Keywords
- Esophagitis, Eosinophilic Esophagitis, Fluticasone, Dysphagia, Safety, Efficacy, Pharmacokinetics, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Glucocorticoids, Orally Disintegrating Tablet
- Medical subject headings
- Eosinophilic Esophagitis, Esophagitis, Deglutition Disorders, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APT-1011Drug
Also called Fluticasone propionate ODT
APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate
PlaceboDrug
Also called Matching placebo dose
Placebo tablets are identical in composition to APT-1011 except they exclude the active ingredient.
| Study group | Role | What they receive |
|---|---|---|
| APT-1011 1.5 mg HS | Experimental | Placebo after breakfast, APT-1011 1.5 mg HS Receives: Drug: APT-1011; Drug: Placebo |
| APT-1011 1.5 mg BID | Experimental | APT-1011 1.5 mg after breakfast, APT-1011 1.5 mg HS Receives: Drug: APT-1011 |
| APT-1011 3 mg HS | Experimental | Placebo after breakfast, APT-1011 3 mg HS Receives: Drug: APT-1011; Drug: Placebo |
| APT-1011 3 mg BID | Experimental | APT-1011 3 mg after breakfast, APT-1011 3 mg HS Receives: Drug: APT-1011 |
| Placebo BID | Placebo comparator | Placebo 30 minutes after breakfast and HS Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Week 12
Secondary outcomes (15)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2017
- Study start22 Jun 2017
- Primary completion3 Jan 2019
- Study completion23 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Eosinophilic EsophagitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adare Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter C Richardson, Study director, Adare Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03191864
- Sponsor's protocol ID
- SP-1011-002
- Other IDs
- 2016-004749-10, 2016
- Acronym
- FLUTE
- Status last verified
- Apr 2023
- First submitted
- 15 Jun 2017
- Last updated
- 26 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 35181572
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03191864
- Acronym / sponsor ID
- FLUTE / SP-1011-002
- Conditions
- Eosinophilic Esophagitis
- Keywords
- Esophagitis, Eosinophilic Esophagitis, Fluticasone, Dysphagia, Safety, Efficacy, Pharmacokinetics, Esophageal Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Adare Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Jun 2017 (actual)
- Primary completion
- 3 Jan 2019 (actual)
- Study completion
- 23 Oct 2019 (actual)
- First posted
- 19 Jun 2017 (actual)
- Results
- Posted 26 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| APT-1011 1.5 mg HS | Experimental | Drug: APT-1011, Drug: PlaceboPlacebo after breakfast, APT-1011 1.5 mg HS |
| APT-1011 1.5 mg BID | Experimental | Drug: APT-1011APT-1011 1.5 mg after breakfast, APT-1011 1.5 mg HS |
| APT-1011 3 mg HS | Experimental | Drug: APT-1011, Drug: PlaceboPlacebo after breakfast, APT-1011 3 mg HS |
| APT-1011 3 mg BID | Experimental | Drug: APT-1011APT-1011 3 mg after breakfast, APT-1011 3 mg HS |
| Placebo BID | Placebo comparator | Drug: PlaceboPlacebo 30 minutes after breakfast and HS |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APT-1011Also: Fluticasone propionate ODTAPT-1011 is an orally disintegrating tablet formulation of fluticasone propionate | Drug | APT-1011 1.5 mg BID, APT-1011 1.5 mg HS, APT-1011 3 mg BID, APT-1011 3 mg HS |
| PlaceboAlso: Matching placebo dosePlacebo tablets are identical in composition to APT-1011 except they exclude the active ingredient. | Drug | APT-1011 1.5 mg HS, APT-1011 3 mg HS, Placebo BID |
Primary outcome
Percentage of Subjects With ≤6 Peak Eosinophils/High-power Field (HPF)
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).
15 secondary outcomes
Percentage of Subjects Who Met the Primary Endpoint at Week 12 and Maintained the Primary Endpoint at Weeks 26 and 52
Time frame: Week 26, and Week 52
Change From Baseline Eosinophilic Esophagitis Endoscopic Reference Score (EREFs) at Week 12, 26, and 52
Time frame: Week 12, Week 26, and Week 52
Percentage of Subjects With a Peak Eosinophils/HPF Number <1 and <15
Time frame: Week 12, Week 26, and Week 52
Change From Baseline Global EoE Symptom Score
Time frame: Week 4, 8, 12, 14, 18, 22, 26, 28, 36, 44, and 52
Change in the Number of Dysphagia Episodes
Time frame: Week 12, Week 26 and Week 52
Change From Baseline 7-Day Eosinophilic Esophagitis Activity Index (EEsAI) Total Score
Time frame: Weeks 12, 26 and 52
Change From Baseline 7-Day Eosinophilic Esophagitis Activity Index (EEsAI) Subscores
Time frame: Weeks 12, 26 and 52
Percentage of Subjects With Mean 7-day EEsAI Total Score <20
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Weeks 12, 26 and 52
Percentage of Subjects Requiring Emergency Endoscopic Food Dis-impaction
Time frame: before Week 14, between Week 14 and Week 28, between Week 28 and Week 52
Percentage of Subjects Requiring Esophageal Dilation
Time frame: baseline to Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35181572Dellon 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter C Richardson study director
Adare Pharmaceuticals, Inc.
75 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APT-1011 in people with Eosinophilic Esophagitis, run by Adare Pharmaceuticals, Inc. at 75 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 sites in United States, Spain, Canada, Germany, Belgium and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects With ≤6 Peak Eosinophils/High-power Field (HPF) (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03191864, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2023.