Study of Fluticasone Propionate MDPI Compared With Fluticasone/Salmeterol MDPI in Adolescent and Adult Patients With Persistent Asthma

Phase 3

Completed

Conditions: Asthma

Interventions: Drug: FS MDPI
Drug: Fp MDPI
Drug: Placebo MDPI
Drug: albuterol/salbutamol
Drug: Beclomethasone dipropionate

Registration Number: NCT02139644

Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

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

Study drug and placebo was 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 787

Inclusion Criteria

Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of their predicted normal value.
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 low-dose inhaled corticosteroid (ICS). The low-dose 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 months before providing consent.
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.
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.
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.
Asthma diagnosis: The patient has a diagnosis of asthma as defined by the National Institutes 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.
The patient is able to perform acceptable and repeatable spirometry.
The patient is able to perform peak expiratory flow (PEF) with a handheld peak flow meter.
The patient is able to use a MDI device without a spacer device and a MDPI device.
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 SV and before all treatment visits.
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.
SABAs: All patients must be able to replace their current SABA with albuterol/salbutamol HFA MDI inhalation aerosol for the duration of the study.
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

A history of a life-threatening asthma exacerbation (an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures).
The patient is pregnant or lactating, or plans to become pregnant during the study period or for 30 days after the study.
The patient has participated as a randomized patient in any investigational drug study within 30 days of the SV.
The patient has previously participated as a randomized patient in a study of Fp MDPI or FS MDPI.
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).
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.
The patient has been treated with any of the prohibited medications during the prescribed (per protocol) washout periods before the SV.
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).
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.
The patient has a history of alcohol or drug abuse within 2 years preceding the SV.
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.
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.
The patient has used immunosuppressive medications within 4 weeks before the SV.
The patient is unable to tolerate or unwilling to comply with the appropriate washout periods and withholding of all applicable medications.
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.
The patient has a history of a positive test for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C infection.
The patient is either an employee or an immediate relative of an employee of the clinical investigational center.
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.
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FS MDPI 100 / 12.5 mcg	albuterol/salbutamol	Patients 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. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
Fp MDPI 50 mcg	albuterol/salbutamol	Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg for a total daily dose of 100 mcg for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
FS MDPI 50 / 12.5 mcg	albuterol/salbutamol	Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. Albuterol/salbutamol 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	albuterol/salbutamol	Patients 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 for 12 weeks. Albuterol/salbutamol 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	FS MDPI	Patients 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. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
FS MDPI 50 / 12.5 mcg	FS MDPI	Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
Fp MDPI 50 mcg	Fp MDPI	Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg for a total daily dose of 100 mcg for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
Placebo MDPI	albuterol/salbutamol	The placebo multidose dry powder inhaler 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). Albuterol/salbutamol 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	Fp MDPI	Patients 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 for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
Placebo MDPI	Placebo MDPI	The placebo multidose dry powder inhaler 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). Albuterol/salbutamol 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	Beclomethasone dipropionate	Patients 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. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
FS MDPI 50 / 12.5 mcg	Beclomethasone dipropionate	Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg (for a total daily dose of 100 mcg) and salmeterol 12.5 mcg (for a total daily dose of 25 mcg) for 12 weeks. Albuterol/salbutamol 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	Beclomethasone dipropionate	Patients 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 for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
Fp MDPI 50 mcg	Beclomethasone dipropionate	Patients took 1 inhalation using a multidose dry powder inhaler (MDPI) twice a day of fluticasone propionate 50 mcg for a total daily dose of 100 mcg for 12 weeks. Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.
Placebo MDPI	Beclomethasone dipropionate	The placebo multidose dry powder inhaler 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). Albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI) was supplied to participants throughout the study to be used as needed as a rescue medication.

Primary Outcome Measures

Name	Time	Method
Standardized Baseline-Adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Effect Curve From Time Zero to 12 Hours Postdose (FEV1 AUEC0-12h) at Week 12	Day 1 (predose, baseline), Week 12 and was performed at the following times relative to the administration of study drug (±5 minutes): 15 and 30 minutes and 1, 2, 3, 4, 6, 8, 10, and 12 hours	A subset of approximately 300 patients who performed postdose serial spirometry is based on sample size calculation. Data from these assessments were used to analyze the primary endpoint of baseline adjusted FEV1 AUEC0-12h at week 12 using the trapezoidal rule based on actual time of measurement. It was standardized by dividing it by the number of hours between the start time of dose administration and the end time of the last nonmissing FEV1 measurement. The baseline FEV1 was the average of the 2 predose FEV1 measurements (30 and 10 minutes predose). If 1 of these was missing, the nonmissing value was used; if both were missing, baseline was treated as missing. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting the baseline FEV1 value.
Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12	Day 1 (predose, baseline), Week 12	Trough FEV1 was a morning spirometry taken predose and pre-rescue bronchodilator. If the patient inadvertently administered asthma medication/study drug at home on the AM of the visit, or if the patient took rescue medication within 6 hours of testing, the visit was rescheduled. The baseline for predose FEV1 was defined as the average of the 30-minute and 10-minute predose measurements obtained at the randomization visit (Day 1).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ(S)) Score at Endpoint for Patients >=18 Years Old	Day 1 (predose, baseline), end of trial (up to week 12)	The AQLQ(S) (September 2010 version; patients aged ≥18 years) was self-administered by the patients at the investigational center at the randomization visit and at Week 12 or end of trial. The questionnaire is a tool to measure the impact of asthma on a patient's quality of life (physical, emotional, social, and occupational) with a recall period of 2 weeks. The AQLQ(S) was administered only to patients 18 years and older. The 32 individual questions in the AQLQ were equally weighted. The overall AQLQ score was the mean of the responses to each of the 32 questions, and ranged from 1 to 7. A score of 7.0 indicated that the patient had no impairments due to asthma and a score of 1.0 indicated severe impairment. Positive change from baseline scores indicate improved quality of life.
Kaplan-Meier Estimate of Probability of Remaining in Study At Week 12	up to Week 12 of the Treatment Period	The analysis of probability of remaining in the study at Week 12 used the time to patient withdrawal for worsening asthma, defined as the number of days elapsed from the date of randomization to the date of withdrawal due to worsening asthma. Patients who were lost to follow-up, who had not withdrawn due to worsening asthma by week 12, or who had withdrawn due to reasons other than worsening asthma were right-censored at the date of last assessment.
Change From Baseline in the Weekly Average of the Daily Morning Trough Peak Expiratory Flow (PEF) Over the 12 Week Treatment	Days -6 to Day 1 (predose), Day 1 (postdose) daily until Week 12	Morning PEF tests were performed before administration of study drug or rescue medications (data were excluded if the time of PEF measurement was more than 5 minutes after the dose time). The patient recorded the highest value of 3 measurements obtained in the patient diary. The baseline PEF was the average value of recorded (nonmissing) morning assessments over the 7 days prior to randomization on Day 1. For efficacy analyses of weekly average morning PEF measurements, values were the averages based on available data for that week.
Change From Baseline in the Weekly Average of the Total Daily Asthma Symptom Score Over the 12-Week Treatment Period	Days -6 to Day 1 (predose, baseline) to Week 12	The total daily asthma symptom score is the average of the daytime and nighttime scores as recorded in the patient diary (range 0-9). Daytime Symptom Score: 0=No symptoms 1. Symptoms for 1 short period 2. Symptoms for 2+ short periods 3. Symptoms for most of the day - did not affect normal daily activities 4. Symptoms for most of the day - did affect normal daily activities 5. Symptoms so severe that I could not go to work or perform normal daily activities Nighttime Symptom Score (determined in the AM): 0=No symptoms 1. Symptoms causing me to wake once (or wake early) 2. Symptoms causing me to wake twice or more (including waking early) 3. Symptoms causing me to be awake for most of the night 4. Symptoms so severe that I did not sleep Baseline was the average of recorded scores over the 7 days before randomization. The change from baseline in the weekly average over weeks 1 to 12 was analyzed using an mixed model for repeated measures (MMRM).
Change From Baseline in the Weekly Average of the Total Daily (24-hour) Use of Albuterol/Salbutamol Inhalation Aerosol Over the 12-Week Treatment Period	Days -6 to Day 1 (predose, baseline), up to week 12	Patients recorded the number of inhalations of rescue medication (albuterol/salbutamol HFA MDI) each AM and PM in the diary. The average number of daily inhalations over the 7 days before the randomization visit was the baseline value. The weekly average was based on the available data for the 7 days before each analysis week. The change from baseline in the weekly average of total daily (24-hour) use of albuterol/ salbutamol inhalation aerosol (number of inhalations) over weeks 1 to 12 was analyzed using a mixed model for repeated measures.
Kaplan-Meier Estimates for Time to 15% and 12% Improvement From Baseline in FEV1 Postdose on Day 1	Day 1 of the Treatment Period (predose and postdose)	A subset of approximately 300 patients who performed postdose serial spirometry is based on sample size calculation. Baseline FEV1 was the average of 2 FEV1 measurements (30 and 10 minutes predose) on Day 1. If one of these was missing, the other measurement was used as baseline value. If both were missing, baseline was treated as missing. Time to target improvement (15% or 12%) was defined as the time elapsed from the time of first dose to the first time the target improvement in FEV1 was achieved. If an exact target increase was not achieved at a measured timepoint, then the time was estimated by linear interpolation between the timepoint when target was reached and the timepoint immediately before. Patients who did not achieve the target improvement were censored at the time of last serial spirometry assessment. Values of 9999 indicate the values could not be estimated which happened when the estimated probability of not achieving target is more than 50%.
Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period	Day 1 to Week 12 of the Treatment Period	An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

Trial Locations

Locations (140): Teva Investigational Site 12584
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Longmont, Colorado, United States
Teva Investigational Site 12379
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Centennial, Colorado, United States
Teva Investigational Site 12586
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Fountain Valley, California, United States
Teva Investigational Site 12381
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Los Angeles, California, United States
Teva Investigational Site 12483
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Lenexa, Kansas, United States
Teva Investigational Site 12596
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Colorado Springs, Colorado, United States
Teva Investigational Site 12386
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Centennial, Colorado, United States
Teva Investigational Site 51141
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Miskolc, Hungary
Teva Investigational Site 90005
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Centurion, South Africa
Teva Investigational Site 90002
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Cape Town, South Africa
Teva Investigational Site 90003
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Middelburg, South Africa
Teva Investigational Site 90008
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Cape Town, South Africa
Teva Investigational Site 12401
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Los Angeles, California, United States
Teva Investigational Site 12394
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Mission Viejo, California, United States
Teva Investigational Site 12395
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Cypress, California, United States
Teva Investigational Site 12490
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Rancho Mirage, California, United States
Teva Investigational Site 12366
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Rolling Hills Estates, California, United States
Teva Investigational Site 12370
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San Jose, California, United States
Teva Investigational Site 12383
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San Diego, California, United States
Teva Investigational Site 12371
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Stockton, California, United States
Teva Investigational Site 12579
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Upland, California, United States
Teva Investigational Site 12997
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Decatur, Georgia, United States
Teva Investigational Site 12480
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Cincinnati, Ohio, United States
Teva Investigational Site 12990
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Cypress, Texas, United States
Teva Investigational Site 12392
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Savannah, Georgia, United States
Teva Investigational Site 12374
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Canton, Ohio, United States
Teva Investigational Site 12494
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Saint Louis, Missouri, United States
Teva Investigational Site 12582
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New Braunfels, Texas, United States
Teva Investigational Site 12373
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Dallas, Texas, United States
Teva Investigational Site 12477
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Waco, Texas, United States
Teva Investigational Site 12402
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El Paso, Texas, United States
Teva Investigational Site 12363
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San Antonio, Texas, United States
Teva Investigational Site 12482
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San Antonio, Texas, United States
Teva Investigational Site 12476
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Encinitas, California, United States
Teva Investigational Site 12591
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Fresno, California, United States
Teva Investigational Site 12372
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Huntington Beach, California, United States
Teva Investigational Site 12365
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Los Angeles, California, United States
Teva Investigational Site 12393
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Riverside, California, United States
Teva Investigational Site 12390
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Miami, Florida, United States
Teva Investigational Site 12992
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Largo, Florida, United States
Teva Investigational Site 12481
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Tallahassee, Florida, United States
Teva Investigational Site 12592
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Shiloh, Illinois, United States
Teva Investigational Site 12588
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Ypsilanti, Michigan, United States
Teva Investigational Site 12595
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Saint Louis, Missouri, United States
Teva Investigational Site 12587
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Brooklyn, New York, United States
Teva Investigational Site 12485
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Rockville Centre, New York, United States
Teva Investigational Site 12475
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Huntersville, North Carolina, United States
Teva Investigational Site 12364
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Raleigh, North Carolina, United States
Teva Investigational Site 12492
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Cincinnati, Ohio, United States
Teva Investigational Site 12488
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Sylvania, Ohio, United States
Teva Investigational Site 12487
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Middleburg Heights, Ohio, United States
Teva Investigational Site 12377
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Edmond, Oklahoma, United States
Teva Investigational Site 12400
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Pittsburgh, Pennsylvania, United States
Teva Investigational Site 12473
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Upland, Pennsylvania, United States
Teva Investigational Site 12389
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Greenville, South Carolina, United States
Teva Investigational Site 12580
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Mount Pleasant, South Carolina, United States
Teva Investigational Site 11067
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Montreal, Quebec, Canada
Teva Investigational Site 54088
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Praha, Czechia
Teva Investigational Site 51143
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Budapest, Hungary
Teva Investigational Site 51134
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Budapest, Hungary
Teva Investigational Site 11068
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Vancouver, Quebec, Canada
Teva Investigational Site 51165
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Dombovar, Hungary
Teva Investigational Site 54084
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Neratovice, Czechia
Teva Investigational Site 54087
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Rokycany, Czechia
Teva Investigational Site 51136
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Nyíregyháza, Hungary
Teva Investigational Site 53221
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Lódz, Poland
Teva Investigational Site 50226
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Ekaterinburg, Russian Federation
Teva Investigational Site 50231
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Saint Petersburg, Russian Federation
Teva Investigational Site 50233
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Voronezh, Russian Federation
Teva Investigational Site 90001
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Johannesburg, South Africa
Teva Investigational Site 90007
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Pretoria, South Africa
Teva Investigational Site 12397
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Birmingham, Alabama, United States
Teva Investigational Site 12376
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Miami, Florida, United States
Teva Investigational Site 12583
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Orlando, Florida, United States
Teva Investigational Site 12594
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Missoula, Montana, United States
Teva Investigational Site 12991
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Knoxville, Tennessee, United States
Teva Investigational Site 12375
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Glendale, Arizona, United States
Teva Investigational Site 51144
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Budapest, Hungary
Teva Investigational Site 12484
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Waterbury, Connecticut, United States
Teva Investigational Site 12491
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Winter Park, Florida, United States
Teva Investigational Site 12399
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Baltimore, Maryland, United States
Teva Investigational Site 12396
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Fall River, Massachusetts, United States
Teva Investigational Site 12493
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Clearwater, Florida, United States
Teva Investigational Site 12384
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North Dartmouth, Massachusetts, United States
Teva Investigational Site 12590
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Waterbury, Connecticut, United States
Teva Investigational Site 12589
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Columbia, Maryland, United States
Teva Investigational Site 12368
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Medford, Oregon, United States
Teva Investigational Site 51133
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Mosdós, Hungary
Teva Investigational Site 12385
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Ocean City, New Jersey, United States
Teva Investigational Site 12585
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North Dartmouth, Massachusetts, United States
Teva Investigational Site 12369
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Rockville, Maryland, United States
Teva Investigational Site 12382
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Portland, Oregon, United States
Teva Investigational Site 12398
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Orangeburg, South Carolina, United States
Teva Investigational Site 12380
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Skillman, New Jersey, United States
Teva Investigational Site 51138
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Szombathely, Hungary
Teva Investigational Site 53187
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Bienkówka, Poland
Teva Investigational Site 53219
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Bydgoszcz, Poland
Teva Investigational Site 53180
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Kraków, Poland
Teva Investigational Site 53220
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Lodz, Poland
Teva Investigational Site 53218
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Tarnów, Poland
Teva Investigational Site 50237
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Yaroslavl, Russian Federation
Teva Investigational Site 58125
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Kharkiv, Ukraine
Teva Investigational Site 58126
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Kharkiv, Ukraine
Teva Investigational Site 12478
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Murray, Utah, United States
Teva Investigational Site 12388
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South Burlington, Vermont, United States
Teva Investigational Site 11065
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Toronto, Ontario, Canada
Teva Investigational Site 51142
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Deszk, Hungary
Teva Investigational Site 51139
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Nyíregyháza, Hungary
Teva Investigational Site 51163
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Sopron, Hungary
Teva Investigational Site 51140
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Debrecen, Hungary
Teva Investigational Site 51145
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Kiskunhalas, Hungary
Teva Investigational Site 51137
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Szeged, Hungary
Teva Investigational Site 51164
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Szigetvár, Hungary
Teva Investigational Site 53182
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Bialystok, Poland
Teva Investigational Site 53188
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Krakow, Poland
Teva Investigational Site 53194
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Poznan, Poland
Teva Investigational Site 53234
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Poznan, Poland
Teva Investigational Site 50227
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Kazan, Russian Federation
Teva Investigational Site 50230
🇷🇺
Novosibirsk, Russian Federation
Teva Investigational Site 53183
🇵🇱
Bialystok, Poland
Teva Investigational Site 53185
🇵🇱
Bialystok, Poland
Teva Investigational Site 53191
🇵🇱
Bialystok, Poland
Teva Investigational Site 53217
🇵🇱
Debica, Poland
Teva Investigational Site 53233
🇵🇱
Strzelce Opolskie, Poland
Teva Investigational Site 53178
🇵🇱
Kraków, Poland
Teva Investigational Site 58128
🇺🇦
Kyiv, Ukraine
Teva Investigational Site 50238
🇷🇺
Moscow, Russian Federation
Teva Investigational Site 53235
🇵🇱
Lodz, Poland
Teva Investigational Site 53237
🇵🇱
Lublin, Poland
Teva Investigational Site 53179
🇵🇱
Tarnów, Poland
Teva Investigational Site 50236
🇷🇺
Chelyabinsk, Russian Federation
Teva Investigational Site 53193
🇵🇱
Warszawa, Poland
Teva Investigational Site 53181
🇵🇱
Wroclaw, Poland
Teva Investigational Site 53189
🇵🇱
Wroclaw, Poland
Teva Investigational Site 58127
🇺🇦
Kyiv, Ukraine
Teva Investigational Site 50234
🇷🇺
Moscow, Russian Federation
Teva Investigational Site 50224
🇷🇺
St. Petersburg, Russian Federation
Teva Investigational Site 58129
🇺🇦
Vinnytsya, Ukraine
Teva Investigational Site 12391
🇺🇸
Bethesda, Maryland, United States
Teva Investigational Site 12378
🇺🇸
Milwaukee, Wisconsin, United States