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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03191864
Recruitment Status : Active, not recruiting
First Posted : June 19, 2017
Last Update Posted : December 13, 2018
Information provided by (Responsible Party):
Adare Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE June 15, 2017
First Posted Date  ICMJE June 19, 2017
Last Update Posted Date December 13, 2018
Actual Study Start Date  ICMJE June 30, 2017
Estimated Primary Completion Date January 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03191864 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • 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
  • 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).
  • 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.
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 16, 2017)
  • HPA axis suppression [ Time Frame: baseline to Week 52 ]
    Number of subjects discontinuing due to HPA axis suppression
  • Candidiasis [ Time Frame: baseline to Week 52 ]
    Frequency of oral and esophageal candidiasis
  • Oral clearance [ Time Frame: Week 12 ]
    Oral clearance (CL/F)
  • Volume of distribution [ Time Frame: Week 12 ]
    Volume of distribution (V/F)
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Efficacy, Safety, and Pharmacokinetics of APT-1011 in Subjects With Eosinophilic Esophagitis (EoE)
Official Title  ICMJE FLUTicasone in Eosinophilic Esophagitis (FLUTE): A Randomized, Double-blind, Placebo-controlled, Dose-ranging, and Maintenance Study of APT-1011 in Subjects With Eosinophilic Esophagitis
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blind
Primary Purpose: Treatment
Condition  ICMJE Eosinophilic Esophagitis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: APT-1011 1.5 mg HS
    Placebo after breakfast, APT-1011 1.5 mg HS
    • Drug: APT-1011
    • Drug: Placebo
  • Experimental: APT-1011 1.5 mg BID
    APT-1011 1.5 mg after breakfast, APT-1011 1.5 mg HS
    Intervention: Drug: APT-1011
  • Experimental: APT-1011 3 mg HS
    Placebo after breakfast, APT-1011 3 mg HS
    • Drug: APT-1011
    • Drug: Placebo
  • Experimental: APT-1011 3 mg BID
    APT-1011 3 mg after breakfast, APT-1011 3 mg HS
    Intervention: Drug: APT-1011
  • Placebo Comparator: Placebo BID
    Placebo 30 minutes after breakfast and HS
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 16, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 30, 2019
Estimated Primary Completion Date January 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Belgium,   Canada,   Germany,   Spain,   Switzerland
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03191864
Other Study ID Numbers  ICMJE SP-1011-002
2016-004749-10 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Adare Pharmaceuticals, Inc.
Study Sponsor  ICMJE Adare Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Peter C Richardson Adare Pharmaceuticals, Inc.
PRS Account Adare Pharmaceuticals, Inc.
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP