Systemic Corticosteroids Avoidance Study in Severe Asthma Patients

A 52-week, Multicenter, Randomized, Double-blind, Double-dummy, Parallel-group, Placebo-controlled Study of Fevipiprant Once Daily Plus Standard-of-care (SoC) for Reduction of Systemic Corticosteroids (Oral and Parenteral) Use in Patients With Severe Asthma

The overall purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to standard-of-care asthma therapy, in terms of avoidance of corticosteroid use over 52 weeks.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: QAW039 150 mg once daily; Drug: QAW039 450 mg once daily; Drug: Placebo once daily

Detailed Description

This was a randomized, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study to determine the ability of fevipiprant (QAW039) plus standard-of-care (SoC) compared with placebo plus SoC to reduce the use of systemic corticosteroids (SCS) in patients with severe asthma. The study included:

• a Screening period of up to 2 weeks to assess eligibility;
• a Run-in period of 4 or 10 weeks to evaluate maintenance of asthma control and to collect baseline safety data. The Run-in period was 4 weeks for patients coming with high-dose ICS/LABA (inhaled corticosteroids/long-acting beta-agonist) and 10 weeks for patients switching from mid-dose to high-dose ICS/LABA as per protocol during the run-in period;
• a Treatment period of 52 weeks. Upon completion of the Run-in period, all patients who met eligibility criteria were randomized to 1 of 3 treatment groups (fevipiprant 150 mg or 450 mg or placebo once daily) in a ratio 1:1:1. Randomized patients were stratified according to their peripheral blood eosinophil count (< 250 cells/μl or ≥ 250 cells/μl);
• a Follow-up period of 2 weeks following the last dose of study drug to collect additional data for safety variables.

The main purpose of this study was to determine the efficacy of fevipiprant (150 mg and 450 mg once daily), compared with placebo, as add-on to GINA (Global Initiative for Asthma) treatment step 4 or 5 SoC asthma therapy in terms of avoidance of SCS use over 52 weeks in patients with inadequately controlled severe asthma and high eosinophil counts (eosinophil count at Visit 1 ≥250 cells/ μl) and in the overall patient population regardless of eosinophil counts.

On 16-Dec-2019 the sponsor decided to terminate study CQAW039A2323 earlier than the planned study completion. There were no safety findings with fevipiprant that contributed to this decision. The planned treatment period of 52 weeks was not completed by any patient; patients were treated for a median time of 14 weeks in each group and a maximum of up to 36 weeks.

• Study Type: Interventional
• Enrollment (Actual): 604
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1428
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1125ABE
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1440BRR
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1012AAR
    • Novartis Investigative Site
  • Buenos Aires, Argentina, 1900
    • Novartis Investigative Site
  • Caba, Argentina
    • Novartis Investigative Site
  • Cordoba, Argentina, X5003DCE
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1122AAK
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1424BSF
      • Novartis Investigative Site
    • Florida, Buenos Aires, Argentina, B1602DQD
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DBS
      • Novartis Investigative Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Novartis Investigative Site
    • San Miguel de Tucuman, Tucuman, Argentina, T4000IFL
      • Novartis Investigative Site
• Belgium
  • Erpent, Belgium, 5100
    • Novartis Investigative Site
  • Lebbeke, Belgium, 9280
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
  • Mechelen, Belgium, 2800
    • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1407
    • Novartis Investigative Site
  • BGR
    • Vidin, BGR, Bulgaria, 3703
      • Novartis Investigative Site
• Chile
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7500692
      • Novartis Investigative Site
  • VII Region Del Maule
    • Curico, VII Region Del Maule, Chile, 3341643
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia, 110221
    • Novartis Investigative Site
  • Bogota, Colombia, 110231
    • Novartis Investigative Site
  • Bucaramanga, Colombia
    • Novartis Investigative Site
  • Cundinamarca
    • Zipaquira, Cundinamarca, Colombia, 250252
      • Novartis Investigative Site
• Czechia
  • Jindrichuv Hradec, Czechia, 377 01
    • Novartis Investigative Site
  • Lovosice, Czechia, 41002
    • Novartis Investigative Site
  • Varnsdorf, Czechia, 40747
    • Novartis Investigative Site
  • CZE
    • Teplice, CZE, Czechia, 415 01
      • Novartis Investigative Site
  • Czech Republic
    • Beroun, Czech Republic, Czechia, 266 01
      • Novartis Investigative Site
    • Praha 4, Czech Republic, Czechia, 140 46
      • Novartis Investigative Site
    • Teplice, Czech Republic, Czechia, 415 01
      • Novartis Investigative Site
• France
  • Grenoble Cedex 9, France, 38043
    • Novartis Investigative Site
  • Pessac Cedex, France, 33604
    • Novartis Investigative Site
  • Herault
    • Montpellier cedex 5, Herault, France, 34059
      • Novartis Investigative Site
  • Rhone
    • Lyon cedex 04, Rhone, France, 69317
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 10717
    • Novartis Investigative Site
  • Berlin, Germany, 10969
    • Novartis Investigative Site
  • Berlin, Germany, 12159
    • Novartis Investigative Site
  • Berlin, Germany, 10119
    • Novartis Investigative Site
  • Berlin, Germany, 13187
    • Novartis Investigative Site
  • Darmstadt, Germany, 64283
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Frankfurt, Germany, 60389
    • Novartis Investigative Site
  • Hamburg, Germany, 20354
    • Novartis Investigative Site
  • Hamburg, Germany, 22299
    • Novartis Investigative Site
  • Hannover, Germany, 30173
    • Novartis Investigative Site
  • Landsberg, Germany, 86899
    • Novartis Investigative Site
  • Leipzig, Germany, 04357
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04275
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Marburg, Germany, 35037
    • Novartis Investigative Site
  • Witten, Germany, 58452
    • Novartis Investigative Site
  • NRW
    • Koblenz, NRW, Germany, 56068
      • Novartis Investigative Site
• Greece
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
    • Athens, GR, Greece, 115 25
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 570 10
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 564 29
      • Novartis Investigative Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Novartis Investigative Site
  • Godollo, Hungary, 2100
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, H-4400
    • Novartis Investigative Site
  • Pecs, Hungary, 7635
    • Novartis Investigative Site
  • Szeged, Hungary, 6722
    • Novartis Investigative Site
  • HUN
    • Gyor, HUN, Hungary, 9024
      • Novartis Investigative Site
    • Hajdunanas, HUN, Hungary, 4080
      • Novartis Investigative Site
    • Kapuvár, HUN, Hungary, 9330
      • Novartis Investigative Site
    • Puspokladany, HUN, Hungary, 4150
      • Novartis Investigative Site
    • Szazhalombatta, HUN, Hungary, 2440
      • Novartis Investigative Site
• Peru
  • Cusco, Peru, 84
    • Novartis Investigative Site
  • Lima, Peru, 1
    • Novartis Investigative Site
  • Piura, Peru
    • Novartis Investigative Site
  • Lima
    • San Isidro, Lima, Peru, 27
      • Novartis Investigative Site
• Philippines
  • Iloilo, Philippines, 5000
    • Novartis Investigative Site
  • Iloilo City, Philippines, 5000
    • Novartis Investigative Site
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Novartis Investigative Site
  • Iloilo
    • Iloilo city, Iloilo, Philippines, 5000
      • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115682
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125993
    • Novartis Investigative Site
  • Petrozavodsk, Russian Federation, 185019
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 198260
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 196143
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 193312
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 194325
    • Novartis Investigative Site
  • Stavropol, Russian Federation, 355000
    • Novartis Investigative Site
  • Volgograd, Russian Federation, 400120
    • Novartis Investigative Site
• Slovakia
  • Zilina, Slovakia, 010 01
    • Novartis Investigative Site
  • Slovak Republic
    • Bardejov, Slovak Republic, Slovakia, 085 01
      • Novartis Investigative Site
    • Humenne, Slovak Republic, Slovakia, 066 01
      • Novartis Investigative Site
    • Levice, Slovak Republic, Slovakia, 934 01
      • Novartis Investigative Site
    • Spisska Nova Ves, Slovak Republic, Slovakia, 052 01
      • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7925
    • Novartis Investigative Site
  • Durban
    • Berea, Durban, South Africa, 4001
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Santiago de Compostela, Spain, 15706
    • Novartis Investigative Site
  • Andalucia
    • Marbella, Andalucia, Spain, 29603
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
• Turkey
  • Mersin, Turkey, 33343
    • Novartis Investigative Site
• United Kingdom
  • Hants
    • Portsmouth, Hants, United Kingdom, PO6 3LY
      • Novartis Investigative Site
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • Novartis Investigative Site
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ
      • Novartis Investigative Site
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Novartis Investigative Site
    • Westminster, California, United States, 92683
      • Novartis Investigative Site
  • Florida
    • Winter Park, Florida, United States, 32789
      • Novartis Investigative Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Novartis Investigative Site
  • Maryland
    • Waldorf, Maryland, United States, 20602
      • Novartis Investigative Site
  • New York
    • Bronx, New York, United States, 10459
      • Novartis Investigative Site
  • Texas
    • Boerne, Texas, United States, 78006
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75230
      • Novartis Investigative Site
    • McKinney, Texas, United States, 75069
      • Novartis Investigative Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Novartis Investigative Site
  • Hanoi, Vietnam, 10000
    • Novartis Investigative Site
  • Ho Chi Minh, Vietnam
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of asthma for a period of at least 3 months prior to Screening Visit with current asthma severity step 4 or 5 (GINA 2018)
• Currently on treatment with medium or high dose ICS/LABA +/- other controller (i.e.long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonist (LTRA) etc. as per GINA) for a minimum of 6 weeks prior to Screening Visit
• At screening, patients with FEV1 of ≤80% of the predicted normal value for the patient, after withholding bronchodilators at Screening Visit and beginning of Run-In Visit
• An increase of ≥12% and ≥200 ml in FEV1 approximately 10 to 15 minutes after administration of 400 mcg of salbutamol/albuterol prior to randomization (documented historical reversibility was accepted).
• Demonstration of inadequate control of asthma based on an ACQ-5 score ≥1.5 at Screening Visit and Treatment Day 1 Visit
• Documented history of at least 1 asthma exacerbation within 1 year prior to enrollment

Exclusion Criteria:

• Asthma exacerbation, within 6 weeks prior to enrollment (screening) that required SCS, hospitalization, or emergency room visit
• Chronic/maintenance use of oral corticosteroids (OCS) for asthma (total OCS use days greater than 6 months; continuously or intermittently) within the last year
• Prior use of biologics that has potential to interfere/ affect asthma disease progression, in the previous 6 months from run-in period.
• Any contraindications of SCS use e.g. diabetes, narrow angle glaucoma, or any other as defined by the treating physician
• Pregnant or nursing (lactating) women
• Use of other investigational drugs within 5 half-lives of enrollment, or [within 30 days], whichever is longer

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QAW039 150 mg; QAW039 150 mg once daily orally	Drug: QAW039 150 mg once daily; QAW039 150 mg once daily (one tablet of blinded QAW039 150 mg to be given together with one tablet blinded placebo to QAW039 450 mg); Other Names: fevipiprant 150 mg
Experimental: QAW039 450 mg; QAW039 450 mg once daily orally	Drug: QAW039 450 mg once daily; QAW039 450 mg once daily (one tablet of blinded QAW039 450 mg to be given together with one tablet blinded placebo to QAW039 150 mg); Other Names: fevipiprant 450 mg
Placebo Comparator: Placebo; Placebo to QAW039 once daily orally	Drug: Placebo once daily; Placebo to QAW039 once daily (one tablet blinded placebo to QAW039 150 mg and one tablet blinded placebo to QAW039 450 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Overall Population	All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120*12/3=480mg total SCS dose. The mean values over 52 weeks in the overall patient population regardless of peripheral blood eosinophil counts are reported here.	52 weeks
Total Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Over 52 Weeks in the Subpopulation of Patients With High Eosinophil Count (≥ 250 Cells/µl)	All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF). Daily use of oral corticosteroids (number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject in the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The total systemic corticosteroids (SCS) dose data was aggregated into monthly data for analysis. For the patients discontinuing treatment early, the total SCS dose for 52 weeks was obtained as annualized SCS dose. For example if patient took 120 mg for 3 months then for 12 months patient will be taking 120*12/3=480mg total SCS dose. The mean values over 52 weeks in the subpopulation of patients with high peripheral blood eosinophil count at baseline are reported here.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daytime Symptom Scores	All participants were provided with an electronic diary (eDiary/ePEF) to record asthma symptom twice per day. Daytime asthma symptoms were assessed before bed and nighttime asthma symptoms on awakening. The daytime asthma symptom score included 4 questions with a range of response categories for each question from 0 to 6 (0 = totally controlled; 6 = extremely poorly controlled). The questions were equally weighted and the overall score (from 0 to 6) was calculated as the average of the 4 questions with higher values indicating more asthma symptoms. Mean values of daytime asthma symptom scores were calculated over 4-week intervals during the treatment period. The baseline values of daytime asthma symptoms scores were defined as the average score during the run-in period. A negative change from baseline in daytime asthma symptom score is a favorable outcome.	Baseline, up to Week 29-32
Change From Baseline in Nighttime Symptom Scores	All participants were provided with an electronic diary (eDiary/ePEF) to record asthma symptom twice per day. Daytime asthma symptoms were assessed before bed and nighttime asthma symptoms on awakening. The nighttime asthma symptom score included 1 question with a range of response categories from 0 to 3 (0 = no awakening with asthma symptoms; 3 = awake all night). Mean values of nighttime asthma symptom scores were calculated over 4-week intervals during the treatment period. The baseline values of nighttime asthma symptoms scores were defined as the average score during the run-in period. A negative change from baseline in nighttime asthma symptom score is a favorable outcome.	Baseline, up to Week 29-32
Change From Baseline in ACQ-5 Total Score up to End of Treatment Visit	The Asthma Control Questionnaire (ACQ-5) was completed by the patients at the investigator's site. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions were equally weighted and the ACQ-5 score was the mean of the 5 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). The baseline values of ACQ-5 score were defined as the ACQ-5 scores obtained on Day 1. A negative change from baseline in ACQ-5 score is a favorable outcome.	Baseline, up to Week 28
Change From Baseline in AQLQ+12 Total Score up to End of Treatment Visit	The Asthma Quality of Life Questionnaire (AQLQ+12) was completed by the patients at the investigator's site. The AQLQ+12 is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma. Patients were asked to recall their experiences during the previous 2 weeks and to score each of the 32 items on a 7-point scale, where 1 indicates maximal impairment and 7 indicates no impairment. Thus, higher scores indicate better asthma-related quality of life. Each item of the AQLQ+12 was equally weighted and the overall score was the mean score of all 32 items and therefore ranged between 1 and 7. The baseline values of AQLQ+12 score were defined as the AQLQ+12 scores obtained on Day 1. A positive change from baseline in AQLQ+12 score is a favorable outcome.	Baseline, up to Week 28
Percentage of Patients Requiring ≥ 7.5 mg Systemic Corticosteroid Dose in mg Prednisone/Prednisolone or Equivalent Per Day Continuously for at Least 30 Days	All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF) to record medication use. Daily use of oral corticosteroids (the number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject using the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The percentage of patients requiring ≥ 7.5 mg systemic corticosteroid dose in mg prednisone/prednisolone (or equivalent) per day continuously for at least 30 days within the on-treatment period is presented in this record.	Up to 36 weeks
Percentage of Patients With no Systemic Corticosteroids Use	All participants were provided with prednisone/prednisolone (or equivalent) tablets that could be used according to the asthma plan along with an electronic diary (e-Diary/ePEF) to record medication use. Daily use of oral corticosteroids (the number of tablets taken in the previous 12 hours) was recorded once in the morning and once in the evening by the subject using the eDiary/PEF device. In case of use of injectable corticosteroids during certain circumstances (eg. hospitalization) the data was collected on the eCRF (electronic case report form). The percentage of patients with no systemic corticosteroids use up to visit on Week 36 is presented in this record.	Week 36
Percentage of Patients With Prescription of Biologic Therapy	As part of the flexible therapy, investigators were allowed to prescribe biologics approved for asthma from randomization visit onwards. Prescription of biologic therapy during the treatment period was recorded. The proportion of patients with prescription of biologic therapy during the on-treatment period is presented in this record.	Up to 36 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2018
• Primary Completion (Actual): February 6, 2020
• Study Completion (Actual): February 6, 2020

Study Registration Dates

• First Submitted: August 9, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Asthma; Bronchial Diseases; Respiratory Tract Diseases; Hypersensitivity; Immune System Diseases; Obstructive Lung Diseases; Lung Diseases; QAW039; Respiratory Hypersensitivity; Fevipiprant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Growth Substances; Plant Growth Regulators; Indoleacetic Acids
• Other Study ID Numbers: CQAW039A2323; 2018-000212-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

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