Efficacy and Safety Study of FP MDPI Compared With FS MDPI in Adolescent and Adult Patients With Persistent Asthma

NCT ID: NCT02141854

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 882 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-09-30

Brief Summary

The primary objective of this study was to evaluate the efficacy of fluticasone propionate (Fp) multidose dry powder inhaler (MDPI) and fluticasone propionate/salmeterol xinafoate (FS) MDPI when administered over 12 weeks in patients 12 years of age and older with persistent asthma.

Detailed Description

Study drug and placebo were supplied in Teva multidose dry powder inhaler (MDPI) devices and provided for participants to use at home. Participants performed spirometry at every visit. Each participant was given a diary at each visit for use until the next visit. Rescue medication (albuterol/salbutamol) was dispensed at each visit, if needed, as determined by the investigational center personnel.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

FS MDPI 200 / 12.5 mcg

Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 200 mcg (for a total daily dose of 400 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Group Type: EXPERIMENTAL

FS MDPI

Intervention Type: DRUG

FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.

During the treatment period, participants were randomized to either fluticasone propionate/salmeterol MDPI 200/12.5 mcg or fluticasone propionate/salmeterol MDPI 100/12.5 mcg twice a day for a total daily dose of 200/25 mcg or 400/25 mcg.

Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Albuterol/salmeterol HFA MDI

Intervention Type: DRUG

Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

FS MDPI 100 / 12.5 mcg

Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 100 mcg (for a total daily dose of 200 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks.

Group Type: EXPERIMENTAL

FS MDPI

Intervention Type: DRUG

FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.

During the treatment period, participants were randomized to either fluticasone propionate/salmeterol MDPI 200/12.5 mcg or fluticasone propionate/salmeterol MDPI 100/12.5 mcg twice a day for a total daily dose of 200/25 mcg or 400/25 mcg.

Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Albuterol/salmeterol HFA MDI

Intervention Type: DRUG

Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Fp MDPI 200 mcg

Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 400 mcg for 12 weeks.

Group Type: EXPERIMENTAL

Fp MDPI

Intervention Type: DRUG

Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.

During the treatment period, participants were randomized to either 200 mcg or 100 mcg of Fp one inhalation twice a day for a total daily dose of 400 mcg or 200 mcg.

Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Albuterol/salmeterol HFA MDI

Intervention Type: DRUG

Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Fp MDPI 100 mcg

Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate (Fp) for a total daily dose of 200 mcg for 12 weeks.

Group Type: EXPERIMENTAL

Fp MDPI

Intervention Type: DRUG

Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.

During the treatment period, participants were randomized to either 200 mcg or 100 mcg of Fp one inhalation twice a day for a total daily dose of 400 mcg or 200 mcg.

Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Albuterol/salmeterol HFA MDI

Intervention Type: DRUG

Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Placebo MDPI

Participants took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of placebo for 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo MDPI

Intervention Type: DRUG

The placebo multidose dry powder inhaler (MDPI) was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart). Patients were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Albuterol/salmeterol HFA MDI

Intervention Type: DRUG

Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Interventions

FS MDPI

FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.

During the treatment period, participants were randomized to either fluticasone propionate/salmeterol MDPI 200/12.5 mcg or fluticasone propionate/salmeterol MDPI 100/12.5 mcg twice a day for a total daily dose of 200/25 mcg or 400/25 mcg.

Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Intervention Type: DRUG

Fp MDPI

Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.

During the treatment period, participants were randomized to either 200 mcg or 100 mcg of Fp one inhalation twice a day for a total daily dose of 400 mcg or 200 mcg.

Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Intervention Type: DRUG

Placebo MDPI

The placebo multidose dry powder inhaler (MDPI) was identical to the devices used to deliver active drug, and indistinguishable from the active treatments. Patients took one inhalation twice a day (approximately 12 hours apart). Patients were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.

Intervention Type: DRUG

Albuterol/salmeterol HFA MDI

Albuterol/salmeterol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Intervention Type: DRUG

Other Intervention Names

fluticasone propionate; inhaled corticosteroid; salmeterol xinafoate; β2 adrenoceptor agonist; fluticasone propionate; inhaled corticosteroid; inert powder; short-acting β2-adrenergic agonists

Eligibility Criteria

Inclusion Criteria

1. Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of their predicted normal value.

2. Current Asthma Therapy: Patients must have a short-acting β2-agonist (for rescue use) for a minimum of 8 weeks before the Screening Visit (SV) and a qualifying dose of an inhaled corticosteroid (ICS). The ICS may be either as ICS monotherapy or as an ICS/long-acting beta agonist (LABA) combination. The ICS component of the patient's asthma therapy should be stable for a minimum of 1 month before providing consent.

3. Reversibility of Disease: Patients must have at least 15% reversibility (all patients) and at least a 200 mL increase from baseline FEV1 (patients age 18 and older) within 30 minutes after 2 to 4 inhalations of albuterol/salbutamol at the SV. Note: Patients who do not qualify for the study due to failure to meet reversibility will be permitted to perform a retest once within 7 days.

4. Patients must provide written informed consent/assent.. For minor patients (ages 12 to 17 years, or as applicable per local regulations), the written ICF must be signed and dated by the parent/legal guardian and the written assent form must be signed and dated by the patient (if applicable). Note: Age requirements are as specified by local regulations.

5. Outpatient >= 12 years of age on the date of consent/assent. In countries where the local regulations permit enrollment of adult patients only, patients must be 18 years of age and older.

6. Asthma diagnosis: The patient has a diagnosis of asthma as defined by the National Institute of Health (NIH). The asthma diagnosis has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in asthma medication) for at least 30 days.

7. The patient is able to perform acceptable and repeatable spirometry.

8. The patient is able to perform peak expiratory flow (PEF) with a handheld peak flow meter.

9. The patient is able to use a metered dose inhaler (MDI) device without a spacer device and a multidose dry powder inhaler (MDPI) device.

10. The patient is able to withhold (as judged by the investigator) his or her regimen of ICS or study drug, and rescue medication for at least 6 hours before the screening visit (SV) and before all treatment visits.

11. The patient/parent/legal guardian/caregiver is capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements.

12. SABAs: All patients must be able to replace their current SABA with albuterol/salbutamol HFA MDI inhalation aerosol for the duration of the study.

13. Female patients may not be pregnant, breastfeeding, or attempting to become pregnant.

• other criteria may apply, please contact the investigator for more information

Exclusion Criteria

1. A history of a life-threatening asthma exacerbation (an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, or hypoxic seizures).

2. The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the study.

3. The patient has participated as a randomized patient in any investigational drug study within 30 days of the SV.

4. The patient has previously participated as a randomized patient in a study of Fp MDPI or FS MDPI.

5. The patient has a known hypersensitivity to any corticosteroid, salmeterol, or any of the excipients in the study drug or rescue medication formulation (ie, lactose).

6. The patient has been treated with any known strong cytochrome P450 (CYP) 3A4 inhibitors (eg, azole antifungals, ritonavir, or clarithromycin) within 30 days before the SV.

7. The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before the SV.

8. The patient currently smokes or has a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient must not have used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco).

9. The patient has a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the SV.

10. The patient has a history of alcohol or drug abuse within 2 years preceding the SV.

11. The patient has had an asthma exacerbation requiring systemic corticosteroids within 30 days before the SV, or has had any hospitalization for asthma within 2 months before the SV.

12. Initiation or dose escalation of immunotherapy (administered by any route) is planned during the study period. However, patients on stable immunotherapy may be considered for inclusion.

13. The patient has used immunosuppressive medications within 4 weeks before the SV.

14. The patient is unable to tolerate or unwilling to comply with the appropriate washout periods and withholding of all applicable medications.

15. The patient has untreated oral candidiasis at the SV. Patients with clinical visual evidence of oral candidiasis who agree to receive treatment and comply with appropriate medical monitoring may enter the study.

16. The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection.

17. The patient is either an employee or an immediate relative of an employee of the clinical investigational center.

18. A member of the patient's household is participating in the study at the same time. However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened.

19. The patient has a disease/condition that in the medical judgment of the investigator would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study.

• other criteria may apply, please contact the investigator for more information

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teva Medical Expert, MD

Role: STUDY_DIRECTOR

Teva Branded Pharmaceutical Products R&D, Inc.

Locations

Teva Investigational Site 12429

Birmingham, Alabama, United States

Teva Investigational Site 12599

Little Rock, Alaska, United States

Teva Investigational Site 12609

Phoenix, Arizona, United States

Teva Investigational Site 12445

Costa Mesa, California, United States

Teva Investigational Site 12454

Encinitas, California, United States

Teva Investigational Site 12456

Fresno, California, United States

Teva Investigational Site 12461

Fullerton, California, United States

Teva Investigational Site 12410

Huntington Beach, California, United States

Teva Investigational Site 12452

Huntington Beach, California, United States

Teva Investigational Site 12417

Long Beach, California, United States

Teva Investigational Site 13017

Mission Viejo, California, United States

Teva Investigational Site 12462

Rancho Mirage, California, United States

Teva Investigational Site 12411

Rolling Hills Estates, California, United States

Teva Investigational Site 13018

San Diego, California, United States

Teva Investigational Site 12413

San Jose, California, United States

Teva Investigational Site 12403

Stockton, California, United States

Teva Investigational Site 12444

Upland, California, United States

Teva Investigational Site 12999

Vista, California, United States

Teva Investigational Site 12405

Centennial, Colorado, United States

Teva Investigational Site 12419

Centennial, Colorado, United States

Teva Investigational Site 13000

Colorado Springs, Colorado, United States

Teva Investigational Site 12459

Waterbury, Connecticut, United States

Teva Investigational Site 13004

Largo, Florida, United States

Teva Investigational Site 12414

Miami, Florida, United States

Teva Investigational Site 12437

Miami, Florida, United States

Teva Investigational Site 12427

Orlando, Florida, United States

Teva Investigational Site 12423

Ormond Beach, Florida, United States

Teva Investigational Site 12604

Panama City, Florida, United States

Teva Investigational Site 13316

Tamarac, Florida, United States

Teva Investigational Site 12606

Winter Park, Florida, United States

Teva Investigational Site 12435

Savannah, Georgia, United States

Teva Investigational Site 13315

Eagle, Idaho, United States

Teva Investigational Site 12439

River Forest, Illinois, United States

Teva Investigational Site 12449

Shiloh, Illinois, United States

Teva Investigational Site 12457

South Bend, Indiana, United States

Teva Investigational Site 12446

Bangor, Maine, United States

Teva Investigational Site 12602

Columbia, Maryland, United States

Teva Investigational Site 12432

Fall River, Massachusetts, United States

Teva Investigational Site 12441

North Dartmouth, Massachusetts, United States

Teva Investigational Site 12466

North Dartmouth, Massachusetts, United States

Teva Investigational Site 13001

Royal Oak, Michigan, United States

Teva Investigational Site 12428

Ypsilanti, Michigan, United States

Teva Investigational Site 13020

Minneapolis, Minnesota, United States

Teva Investigational Site 12451

Columbia, Missouri, United States

Teva Investigational Site 12421

Rolla, Missouri, United States

Teva Investigational Site 12412

St Louis, Missouri, United States

Teva Investigational Site 12453

St Louis, Missouri, United States

Teva Investigational Site 12610

Missoula, Montana, United States

Teva Investigational Site 13021

Las Vegas, Nevada, United States

Teva Investigational Site 12409

Skillman, New Jersey, United States

Teva Investigational Site 12464

Brooklyn, New York, United States

Teva Investigational Site 12603

The Bronx, New York, United States

Teva Investigational Site 12430

Charlotte, North Carolina, United States

Teva Investigational Site 12407

Raleigh, North Carolina, United States

Teva Investigational Site 12415

Canton, Ohio, United States

Teva Investigational Site 12455

Cincinnati, Ohio, United States

Teva Investigational Site 12463

Cincinnati, Ohio, United States

Teva Investigational Site 12460

Middleburg Heights, Ohio, United States

Teva Investigational Site 12426

Edmond, Oklahoma, United States

Teva Investigational Site 13008

Oklahoma City, Oklahoma, United States

Teva Investigational Site 12406

Medford, Oregon, United States

Teva Investigational Site 12442

Portland, Oregon, United States

Teva Investigational Site 12563

Normal Square, Pennsylvania, United States

Teva Investigational Site 12443

Pittsburgh, Pennsylvania, United States

Teva Investigational Site 12438

Upland, Pennsylvania, United States

Teva Investigational Site 12408

Charleston, South Carolina, United States

Teva Investigational Site 12431

Greenville, South Carolina, United States

Teva Investigational Site 12465

Mt. Pleasant, South Carolina, United States

Teva Investigational Site 12467

Mt. Pleasant, South Carolina, United States

Teva Investigational Site 12420

Orangeburg, South Carolina, United States

Teva Investigational Site 12433

Rock Hill, South Carolina, United States

Teva Investigational Site 13003

Knoxville, Tennessee, United States

Teva Investigational Site 12425

Arlington, Texas, United States

Teva Investigational Site 12416

Dallas, Texas, United States

Teva Investigational Site 12418

Dallas, Texas, United States

Teva Investigational Site 12440

El Paso, Texas, United States

Teva Investigational Site 12447

Killeen, Texas, United States

Teva Investigational Site 13318

San Antonio, Texas, United States

Teva Investigational Site 13002

Sugar Land, Texas, United States

Teva Investigational Site 12424

Waco, Texas, United States

Teva Investigational Site 12422

South Burlington, Vermont, United States

Teva Investigational Site 12605

Richmond, Virginia, United States

Teva Investigational Site 12436

Spokane, Washington, United States

Teva Investigational Site 12564

Tacoma, Washington, United States

Teva Investigational Site 12448

Greenfield, Wisconsin, United States

Teva Investigational Site 11072

Toronto, Ontario, Canada

Teva Investigational Site 11075

Vancouver, Quebec, Canada

Teva Investigational Site 54096

Jindřichův Hradec, , Czechia

Teva Investigational Site 54098

Prague, , Czechia

Teva Investigational Site 54095

Rokycany, , Czechia

Teva Investigational Site 54094

Strakonice, , Czechia

Teva Investigational Site 51149

Budapest, , Hungary

Teva Investigational Site 51155

Budapest, , Hungary

Teva Investigational Site 51157

Budapest, , Hungary

Teva Investigational Site 51161

Budapest, , Hungary

Teva Investigational Site 51154

Debrecen, , Hungary

Teva Investigational Site 51152

Deszk, , Hungary

Teva Investigational Site 51170

Dombóvár, , Hungary

Teva Investigational Site 51158

Kiskunhalas, , Hungary

Teva Investigational Site 51153

Miskolc, , Hungary

Teva Investigational Site 51156

Mosdós, , Hungary

Teva Investigational Site 51150

Nyíregyháza, , Hungary

Teva Investigational Site 51151

Nyíregyháza, , Hungary

Teva Investigational Site 51148

Százhalombatta, , Hungary

Teva Investigational Site 51146

Szeged, , Hungary

Teva Investigational Site 51162

Szigetvár, , Hungary

Teva Investigational Site 51147

Szombathely, , Hungary

Teva Investigational Site 51176

Tatabánya, , Hungary

Teva Investigational Site 51177

Törökbálint, , Hungary

Teva Investigational Site 53199

Bialystok, , Poland

Teva Investigational Site 53200

Bialystok, , Poland

Teva Investigational Site 53202

Bialystok, , Poland

Teva Investigational Site 53208

Bialystok, , Poland

Teva Investigational Site 53210

Bydgoszcz, , Poland

Teva Investigational Site 53227

Bydgoszcz, , Poland

Teva Investigational Site 53225

Dębica, , Poland

Teva Investigational Site 53203

Gdansk, , Poland

Teva Investigational Site 53195

Krakow, , Poland

Teva Investigational Site 53197

Krakow, , Poland

Teva Investigational Site 53205

Krakow, , Poland

Teva Investigational Site 53228

Lodz, , Poland

Teva Investigational Site 53240

Lodz, , Poland

Teva Investigational Site 53201

Lódz, , Poland

Teva Investigational Site 53229

Lódz, , Poland

Teva Investigational Site 53241

Lublin, , Poland

Teva Investigational Site 53206

Poznan, , Poland

Teva Investigational Site 53211

Poznan, , Poland

Teva Investigational Site 53230

Strzelce Opolskie, , Poland

Teva Investigational Site 53196

Tarnów, , Poland

Teva Investigational Site 53222

Warsaw, , Poland

Teva Investigational Site 53198

Wroclaw, , Poland

Teva Investigational Site 53224

Wroclaw, , Poland

Teva Investigational Site 50255

Chelyabinsk, , Russia

Teva Investigational Site 50241

Kazan', , Russia

Teva Investigational Site 50250

Moscow, , Russia

Teva Investigational Site 50252

Moscow, , Russia

Teva Investigational Site 50242

Saint Petersburg, , Russia

Teva Investigational Site 50245

Saint Petersburg, , Russia

Teva Investigational Site 50246

Saint Petersburg, , Russia

Teva Investigational Site 50254

Saratov, , Russia

Teva Investigational Site 50244

Tomsk, , Russia

Teva Investigational Site 50251

Voronezh, , Russia

Teva Investigational Site 50275

Yaroslavl, , Russia

Teva Investigational Site 50243

Yekaterinburg, , Russia

Teva Investigational Site 90011

Berea, , South Africa

Teva Investigational Site 90015

Bloemfontein, , South Africa

Teva Investigational Site 90012

Cape Town, , South Africa

Teva Investigational Site 90013

Centurion, , South Africa

Teva Investigational Site 90016

Middelburg, , South Africa

Teva Investigational Site 90014

Pretoria, , South Africa

Teva Investigational Site 12404

Papillion, NE, Thailand

Teva Investigational Site 58133

Kharkiv, , Ukraine

Teva Investigational Site 58135

Kharkiv, , Ukraine

Teva Investigational Site 58132

Kyiv, , Ukraine

Countries

Germany; United States; Canada; Czechia; Hungary; Poland; Russia; South Africa; Thailand; Ukraine

References

Sher LD, Yiu G, Sakov A, Liu S, Caracta CF. Fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers compared with placebo for persistent asthma. Allergy Asthma Proc. 2017 Sep 21;38(5):343-353. doi: 10.2500/aap.2017.38.4069. Epub 2017 Jun 21.

Reference Type: DERIVED

PMID: 28639542 (View on PubMed)

Miller DS, Yiu G, Hellriegel ET, Steinfeld J. Dose-ranging study of salmeterol using a novel fluticasone propionate/salmeterol multidose dry powder inhaler in patients with persistent asthma. Allergy Asthma Proc. 2016 Jul;37(4):291-301. doi: 10.2500/aap.2016.37.3963. Epub 2016 May 27.

Reference Type: DERIVED

PMID: 27216137 (View on PubMed)

Other Identifiers

2014-000923-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FSS-AS-30017

Identifier Type: -

Identifier Source: org_study_id