A Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD

Phase 3

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Placebo; Drug: Ensifentrine

• Registration Number: NCT04542057
• Lead Sponsor: Verona Pharma plc

Brief Summary

The purpose of this study is to determine if ensifentrine is safe and effective for the treatment of patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-01
• Study First Submitted QC: 2020-09-08
• Study First Posted: 2020-09-09
• Study Start: 2020-09-22
• Primary Completion: 2022-05-03
• Study Completion: 2022-07-06
• Results First Submitted: 2023-06-19
• Results First Submitted QC: 2023-07-21
• Results First Posted: 2023-07-24
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 790

Inclusion Criteria

Informed Consent

1. Capable of giving informed consent indicating that they understand the purpose of the study and study procedures and agree to comply with the requirements and restrictions listed in the informed consent form (ICF).

   Age and Sex

2. Age: Patient must be 40 to 80 years of age inclusive, at the time of Screening.

3. Sex:

   • Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.

   • Females are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions apply:

     1. Not a woman of childbearing potential (WOCBP). Or
     2. A WOCBP who agrees to follow the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.

   Smoking History

4. Smoking History: Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years at Screening (Visit 0) [number of pack years = (number of cigarettes per day / 20) × number of years smoked (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 0. Smoking cessation programs are permitted during the study.

   COPD Diagnosis, Symptoms, Severity and Maintenance Therapy

5. COPD Diagnosis: Patients with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli BR, 2004) with symptoms compatible with COPD.

6. COPD Symptoms: A score of ≥2 on the Modified Medical Research Council (mMRC) Dyspnea Scale.

7. COPD Severity:

   1. Pre- and Post-albuterol/salbutamol FEV1/FVC ratio of <0.70.
   2. Post-albuterol/salbutamol FEV1 ≥30 % and ≤70% of predicted normal calculated using the National Health and Nutrition Examination Survey III.

8. Maintenance Therapy: Patients on no maintenance/background therapy or patients on stable maintenance LAMA or LABA therapy are eligible. Patients taking maintenance LAMA or LABA therapy must demonstrate stable use of the maintenance LAMA or LABA therapy for at least 3 months prior to Screening and agree to continue use for the duration of the study. Background maintenance LAMA or LABA bronchodilator therapy will be capped at 50% of patients.

   Other Requirements for Inclusion

9. Capable of withholding SABAs for 4 hours prior to initiation of any spirometry. Patients in the maintenance LAMA or LABA therapy stratum must be capable of withholding Twice-Daily maintenance LAMA or LABA for 24 hours and Once-Daily maintenance LAMA or LABA for 48 hours prior to initiation of any spirometry.

10. Capable of using the study nebulizer correctly and complying with all study restrictions and procedures.

11. Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines.

Randomization Criteria Criteria for Inclusion at Randomization

1. Symptoms of COPD: A score of ≥2 on the mMRC Dyspnea Scale.
2. Completion of the e-Diary at least 5 of the last 7 days of the Run-in period.

Exclusion Criteria

Current Condition or Medical History

1. History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.

2. Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening and/or a positive COVID-19 test result indicating an active infection at Screening. Patients with COVID-19 antibodies from a previous exposure with no active infection are not excluded.

3. COPD exacerbation requiring oral or parenteral steroids within 3 months of Screening.

4. Previous lung resection or lung reduction surgery within 1-year of Screening.

5. Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day. As needed oxygen use (≤12 hours per day) is not exclusionary.

6. Pulmonary rehabilitation, unless such treatment has been in a stable maintenance phase for 4 weeks prior to Visit 1 and remains stable during the study.

7. Lower respiratory tract infection within 6 weeks of Screening.

8. Other respiratory disorders including, but not limited to, a current diagnosis of asthma, active tuberculosis, lung cancer, sarcoidosis, lung fibrosis, interstitial lung diseases, unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary diseases.

9. Major surgery (requiring general anesthesia) in the 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.

10. Historical or current evidence of clinically significant cardiovascular disease defined as any disease that in the opinion of the Investigator would put the safety of the patient at risk through participation or which could affect the efficacy or safety analysis if the disease/condition were to exacerbate during the study, including, but not limited to:

    • Myocardial infarction or unstable angina within 6 months prior to Screening.
    • Unstable or life-threatening cardiac arrhythmia requiring intervention within 3 months prior to Screening.
    • Diagnosis of New York Heart Association Class III and Class IV heart failure.

11. Chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant.

12. Unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).

13. History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin.

14. Findings on physical examination that an investigator considers to be clinically significant at Screening.

    Prior/Concomitant Therapy

15. Use of prohibited medications within the time intervals

    History or Suspicion of Drug or Alcohol Abuse

16. Current or history of past drug or alcohol abuse within the past 5 years.

    Laboratory and Other Diagnostic Parameters

17. Glomerular Filtration Rate (eGFR) <30 mL/min. The Chronic Kidney Disease Epidemiology Collaboration Creatinine (2009) calculation will be used.

18. Alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

19. Hepatitis B antibody:

    • Positive findings for both Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (anti-HBc) are excluded, as this indicates acute or chronic infection.
    • Negative findings for HBsAg and Hepatitis B surface antibody (anti-HBs) but positive findings for anti-HBc are excluded as this may indicate current or resolving infection.
    • Positive findings for anti-HBc and anti-HBs but negative findings for HBsAg are not excluded, as this indicates immunity due to natural infection.
    • Positive findings for anti-HBs but negative findings for HBsAg and anti-HBc are not excluded, as this indicates immunity due to hepatitis B vaccination.

20. Hepatitis C antibody positive.

21. Any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal. Abnormal chemistry and/or hematology may be repeated during Screening.

22. Chest X-ray (CXR; posterior-anterior) at Screening, or in the 12 months prior to Screening with clinically significant abnormalities not attributable to COPD. If a CXR within the past 12 months is not available but a computerized tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR. For subjects in Germany, if a CXR or CT scan is not available in the 12 months prior to Screening, the subject is not eligible for the study.

23. Electrocardiogram (ECG) finding that is significantly abnormal on the 12-lead ECG obtained at Screening.

    Other Exclusions

24. Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical trial within 30 days prior to Screening.

25. Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical trial within 30 days prior to Screening.

26. Intolerance or hypersensitivity to albuterol/salbutamol or ensifentrine (RPL554) or any of its excipients/components.

27. Prior receipt of blinded study medication in an ensifentrine (RPL554) study.

28. Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned.

29. Inability to read, understand, and/or complete questionnaires (in the opinion of the Investigator).

30. A disclosed history or one known to the Investigator of significant non-compliance in previous investigational studies or with prescribed medications.

31. Any other reason that the Investigator considers makes the patient unsuitable to participate.

Criteria for Exclusion from Randomization

1. COPD exacerbation or lower respiratory tract infection between Screening and Randomization (defined as use of any additional treatment other than current treatment and rescue medication and/or emergency department or hospital visit). Patients with a severe COPD exacerbation that requires hospitalization may not be rescreened.
2. Positive COVID-19 result at Screening or between Screening and Randomization.
3. Prohibited medication use between Screening Visit 0 and Visit 1.
4. Significantly abnormal ECG finding on the 12-lead ECG obtained at Screening as assessed by the investigator or site medical doctor/medically qualified person or on the pre-dose (prior to randomization) ECG obtained at Visit 1. In the event that the central ECG reviewer discovers a significant ECG abnormality on the Visit 1 ECG, the patient will be discontinued.
5. Did not meet one or more of the Inclusion Criteria or met one or more of the Exclusion Criteria.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2	Placebo	Ensifentrine Placebo Nebulized Solution; twice daily for 24 weeks
Arm 1	Ensifentrine	Ensifentrine Nebulized Suspension; 3 mg twice daily for 24 weeks

Primary Outcome Measures

Name	Time	Method
Least Square (LS) Mean Change From Baseline in Average Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12h) at Week 12	Baseline (40 minutes before first administration on Day 1) and Week 12	Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-12h was defined as AUC over 12 hours of the FEV1, divided by 12 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.

Secondary Outcome Measures

Name	Time	Method
LS Mean Change From Baseline FEV1 to Peak FEV1 at Day 1 and Weeks 6, 12 and 24	Baseline (40 minutes before first administration on Day 1), post-dose on Day 1, Weeks 6, 12, and 24	Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Peak FEV1 is the maximum value in the 4 hours after dosing. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
LS Mean Change From Baseline to the Mean Weekly Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24	Baseline (average of 7 days before first administration on Day 1) and Weeks 6, 12, and 24	The E-RS scale consists of 11 questions, with 3 sub-domains of: breathlessness, cough and sputum, and chest symptoms. The E-RS sub-domain score was calculated as the sum from the relevant questions. The E-RS total score was derived as the sum of the raw scores of the 11 items ranging from 0 to 40. Higher scores indicates severe respiratory symptoms. Scores were derived weekly as the mean over 7 days prior to the visit, using only days where data was recorded. The E-RS was collected daily by electronic diary (e-diary). Baseline is the mean over the 7 days prior to the first intake of study medication, using only days where data was recorded.
LS Mean Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 6, 12 and 24	Baseline (40 minutes before first administration on Day 1) and Weeks 6, 12, and 24	The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Score ranging from 0 to 100 and higher scores indicated a worse outcome. Baseline is the score calculated on Day 1 prior to 4 hour post-dose spirometry.
LS Mean Change From Baseline FEV1 to Morning Trough FEV1 at Weeks 6, 12 and 24	Baseline (40 minutes before first administration on Day 1) and Weeks 6, 12, and 24	Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Morning trough FEV1 was the last value collected prior to the morning dose. Baseline FEV1 is the mean of the two measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
LS Mean Change From Baseline in Average FEV1 Area Under the Curve Over 4 Hours (AUC0-4h) at Day 1 and Weeks 6, 12 and 24	Baseline (40 minutes before first administration on Day 1), post-dose on Day 1, Weeks 6, 12, and 24	Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Average FEV1 AUC0-4h was defined as area under the curve over 4 hours of the FEV1, divided by 4 hours. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on Day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Percentage of SGRQ Responders at Weeks 6, 12 and 24	Weeks 6, 12 and 24	The SGRQ questionnaire consists of 17 questions, split into 2 parts. Part 1 consisted of the first 8 questions and was related to the symptoms subdomain. The remaining 9 questions were in Part 2, which were related to the activity and impacts subdomains. The total score was calculated by dividing the summed weights by the maximum possible weight for all items in the questionnaire and expressing the result as a percentage. Responder was a patient with an improvement from baseline in SGRQ total score of 4 or more. Percentage of SGRQ responders are reported.
LS Mean Change From Baseline to the Mean Weekly Rescue Medication Use at Weeks 6, 12 and 24	Baseline (average of 7 days before first administration on Day 1) and Weeks 6, 12, and 24	Use of rescue medication (albuterol/salbutamol) per week was calculated as the LS mean use daily over 7 days. Daily rescue medication use was collected in an e-diary throughout the study. Baseline is the mean over the 7 days prior to the first intake of study medication, calculated as the sum of puffs taken, divided by number of days data has been recorded.
LS Mean Transition Dyspnea Index (TDI) Questionnaire Total Score at Weeks 6, 12 and 24	Weeks 6, 12 and 24	The TDI is a questionnaire that focused on 3 sub-domains: functional impairment, magnitude of task and magnitude of effort. Sub-domain score was calculated as the sum from the related questions. Total score was calculated as the sum of the sub-domain scores. The TDI measures the change in dyspnea severity from the baseline as measured by the baseline dyspnea index. It was rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement). Higher scores indicate better outcome. Change from baseline was assessed with the Baseline Dyspnea Index.
LS Mean Change From Baseline FEV1 to Evening Trough FEV1 at Week 12	Baseline (40 minutes before first administration on Day 1) and Week 12	Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Evening trough FEV1 was the value collected at 12 hours post-morning dose and prior to the evening dose. Baseline FEV1 is the mean of the 2 measurements taken before study medication on the day of first dosing, that is, \<=40 minutes pre-dose on day 1. Spirometry assessments were performed in accordance with ATS/ERS guidelines.

Trial Locations

Locations (128)

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Clinical Trials of Florida. LLC; 🇺🇸 Miami, Florida, United States

Research Institute of South Florida; 🇺🇸 Miami, Florida, United States

Advanced Medical Research Institute; 🇺🇸 Miami, Florida, United States

Integrated Research Center; 🇺🇸 San Diego, California, United States

Institute of HealthCare Assessment, Inc.; 🇺🇸 San Diego, California, United States

Diagnostics Research Group; 🇺🇸 San Antonio, Texas, United States

Ostrowieckie Centrum Medyczne spółka cywilna Anna Olech-Cudzik, Krzysztof Cudzik; 🇵🇱 Ostrowiec Świętokrzyski, Poland

"ALL-MED" Specjalistyczna Opieka Medyczna, Medyczny Instytut Badawczy; 🇵🇱 Wrocław, Poland

Univerzitna nemocnica Martin, Klinika pneumologie a ftizeologie; 🇸🇰 Martin, Slovakia

SHATPPD - Vratsa, EOOD; 🇧🇬 Vratsa, Bulgaria

Szarvasi Tüdőgyógyász Kft; 🇭🇺 Szarvas, Hungary

Centrum Badań Klinicznych Piotr Napora Lekarze Spółka Partnerska; 🇵🇱 Wrocław, Poland

Medical Center- Prolet Ltd; 🇧🇬 Ruse, Bulgaria

Komlói Egészségcentrum, Bányászati Utókezelő és Éjjeli Szanatórium Egészségügyi Központ; 🇭🇺 Komló, Hungary

Da Vinci Klinika Infer-Med Kft. Tüdőgyógyászat; 🇭🇺 Pécs, Hungary

Hospital Vithas Internacional Xanit; 🇪🇸 Benalmádena, Málaga, Spain

SHATPPD - Pazardzhik, EOOD; 🇧🇬 Pazardzhik, Bulgaria

Csanád-Csongrád Megyei Mellkasi Betegségek Szakkórháza, Tüdőgondozó Intézet; 🇭🇺 Szeged, Hungary

Prywatny Gabinet Lekarski; 🇵🇱 Rzeszów, Poland

Zeleznicna nemocnica s poliklinikou; 🇸🇰 Košice, Slovakia

Medical Centre "Asklepii", OOD; 🇧🇬 Dupnitsa, Bulgaria

MHAT 'Dr. Stamen Iliev', AD; 🇧🇬 Montana, Bulgaria

SHATPPD-Ruse EOOD; 🇧🇬 Ruse, Bulgaria

NMTH "Tsar Boris III"; 🇧🇬 Sofia, Bulgaria

DCC "Alexandrovska", EOOD; 🇧🇬 Sofia, Bulgaria

Diagnostic Consultation Center CONVEX EOOD; 🇧🇬 Sofia, Bulgaria

Carolina Research Center, Inc.; 🇺🇸 Shelby, North Carolina, United States

SHATPPD "Dr. Treyman" EOOD; 🇧🇬 Veliko Tarnovo, Bulgaria

Dynamic Drug Advancement; 🇨🇦 Ajax, Ontario, Canada

Centrum Medyczne All-Med; 🇵🇱 Kraków, Poland

DM Clinical Research; 🇺🇸 Tomball, Texas, United States

Medical Center "ResearchExpert", OOD; 🇧🇬 Varna, Bulgaria

Małopolskie Centrum Alergologii; 🇵🇱 Kraków, Poland

Jasper Summit Research LLC; 🇺🇸 Jasper, Alabama, United States

Alpine Clinical Research Center; 🇺🇸 Boulder, Colorado, United States

Medical Research of Central Florida; 🇺🇸 Leesburg, Florida, United States

Innovative Research of West Florida; 🇺🇸 Clearwater, Florida, United States

Manassas Clinical Research Center; 🇺🇸 Manassas, Virginia, United States

Private Practice RESPISOM Namur; 🇧🇪 Namur, Belgium

Synergy Respiratory Care; 🇨🇦 Sherwood Park, Alberta, Canada

Pneumologicko-ftizeologická ambulancia, Pneumomed, s.r.o; 🇸🇰 Bratislava, Slovakia

CU Pharmaceutical Research; 🇺🇸 Union, South Carolina, United States

Minnesota Lung Center; 🇺🇸 Woodbury, Minnesota, United States

TTS Research; 🇺🇸 Boerne, Texas, United States

Gabinet Pulmonologii i Diagnostyki Chorób Alergicznych; 🇵🇱 Szczecin, Poland

Ambulancia pneumologie a ftizeologie, ZAPA JJ, s.r.o.; 🇸🇰 Levice, Slovakia

Hvidovre Hospital; 🇩🇰 Hvidovre, Denmark

Clinical Research of Gastonia; 🇺🇸 Gastonia, North Carolina, United States

Genesis Clin RES& Consulting; 🇺🇸 Fall River, Massachusetts, United States

ETG Łódź; 🇵🇱 Łódź, Poland

Zealand University Hospital, Roskilde; 🇩🇰 Roskilde, Denmark

Piedmont Research Partners; 🇺🇸 Fort Mill, South Carolina, United States

MHAT "Lyulin", EAD; 🇧🇬 Sofia, Bulgaria

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD; 🇧🇬 Stara Zagora, Bulgaria

AMR New Orleans; 🇺🇸 New Orleans, Louisiana, United States

Accel Research Sites - DeLand Clinical Research Unit; 🇺🇸 DeLand, Florida, United States

South Medical Research Group, Inc.; 🇺🇸 Miami, Florida, United States

Axcess Medical Research; 🇺🇸 Loxahatchee Groves, Florida, United States

ProCare Clinical Research; 🇺🇸 Miami Gardens, Florida, United States

Monroe Biomedical Research; 🇺🇸 Monroe, North Carolina, United States

Odense Universitetshospital; 🇩🇰 Odense C, Denmark

Montana Medical Research Inc.; 🇺🇸 Missoula, Montana, United States

Downtown LA Research Center, Inc.; 🇺🇸 Los Angeles, California, United States

MultiSpecialty Clinical Research, Inc.; 🇺🇸 Johnson City, Tennessee, United States

UZA; 🇧🇪 Edegem, Belgium

Tartu University Hospital, Lung Clinic; 🇪🇪 Tartu, Estonia

Dr. Kenessey Albert Kórház-Rendelőintézet, Pulmonológiai Osztály; 🇭🇺 Balassagyarmat, Hungary

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Institut Catala de Serveis Medics; 🇪🇸 Girona, Spain

Aventiv Research Inc.; 🇺🇸 Columbus, Ohio, United States

Remington Davis Clinical Research; 🇺🇸 Columbus, Ohio, United States

VitaLink Research - Greenville; 🇺🇸 Greenville, South Carolina, United States

VitaLink Research Anderson; 🇺🇸 Anderson, South Carolina, United States

C.H.R. de la Citadelle; 🇧🇪 Liège, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

MHAT 'Puls' AD; 🇧🇬 Blagoevgrad, Bulgaria

VitaLink Research Gaffney; 🇺🇸 Gaffney, South Carolina, United States

SHATPD Pernik; 🇧🇬 Pernik, Bulgaria

University First MHAT-Sofia, "St. Joan Krastitel" EAD; 🇧🇬 Sofia, Bulgaria

Fifth MHAT - Sofia EAD; 🇧🇬 Sofia, Bulgaria

Metroplex Pulmonary and Sleep Center; 🇺🇸 McKinney, Texas, United States

MC "Tara", OOD; 🇧🇬 Veliko Tarnovo, Bulgaria

Pulmonary Associates Clinical Trials; 🇺🇸 Phoenix, Arizona, United States

Elite Clinical Studies LLC; 🇺🇸 Phoenix, Arizona, United States

C.I.C. Mauricie Inc.; 🇨🇦 Trois-Rivières, Quebec, Canada

Clinical Research of West Florida, Inc.; 🇺🇸 Tampa, Florida, United States

Clinical Research Trials of Florida, Inc.; 🇺🇸 Tampa, Florida, United States

California Medical Research Associates; 🇺🇸 Northridge, California, United States

Sarasota Clinical Research; 🇺🇸 Sarasota, Florida, United States

Coastal Pulmonary Critical Care; 🇺🇸 Saint Petersburg, Florida, United States

Element Research Group; 🇺🇸 San Antonio, Texas, United States

PnP Research; 🇺🇸 Amarillo, Texas, United States

Wright Clinical Research, LLC; 🇺🇸 Alabaster, Alabama, United States

Clinical Research Institute of Arizona, LLC; 🇺🇸 Sun City West, Arizona, United States

SEC Clinical Research; 🇺🇸 Andalusia, Alabama, United States

Premier Medical Group; 🇺🇸 Bakersfield, California, United States

Antelope Valley Clinical Trials; 🇺🇸 Lancaster, California, United States

Riverside Clinical Research; 🇺🇸 Edgewater, Florida, United States

Pasadena Center for Medical Research, LLC; 🇺🇸 Saint Petersburg, Florida, United States

Florida Pulmonary Research Institute, LLC; 🇺🇸 Winter Park, Florida, United States

Mid Hudson Medical Research; 🇺🇸 New Windsor, New York, United States

CHEAR Center LLC; 🇺🇸 Bronx, New York, United States

American Health Research; 🇺🇸 Charlotte, North Carolina, United States

Carolina Clinical Research; 🇺🇸 Charlotte, North Carolina, United States

Clinical Research of Lake Norman; 🇺🇸 Mooresville, North Carolina, United States

PharmQuest LLC; 🇺🇸 Greensboro, North Carolina, United States

OK Clinical Research, LLC; 🇺🇸 Edmond, Oklahoma, United States

Aventiv Research; 🇺🇸 Dublin, Ohio, United States

Velocity Clinical Research, Medford (Crisor, LLC); 🇺🇸 Medford, Oregon, United States

Safe Harbor Clinical Research; 🇺🇸 East Providence, Rhode Island, United States

Spartanburg Medical Research; 🇺🇸 Spartanburg, South Carolina, United States

VitaLink Research Spartanburg; 🇺🇸 Spartanburg, South Carolina, United States

New Phase Research Development; 🇺🇸 Knoxville, Tennessee, United States

Houston Pulmonary and Sleep Allergy and Asthma Associates; 🇺🇸 Cypress, Texas, United States

Corsicana Medical Research, PLLC; 🇺🇸 Corsicana, Texas, United States

Sherman Clinical Research; 🇺🇸 Sherman, Texas, United States

Respirology and Rheumatology Associates; 🇨🇦 Windsor, Ontario, Canada

ALTA Clinical Research Inc.; 🇨🇦 Edmonton, Alberta, Canada

Szent Borbála Kórház, Tüdőgyógyászat; 🇭🇺 Tatabánya, Hungary

Hospital Clinico Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Midwest Chest Consultants; 🇺🇸 Saint Charles, Missouri, United States

VitaLink Research Columbia; 🇺🇸 Columbia, South Carolina, United States

Center for Clinical Trials of Sacramento, Inc.; 🇺🇸 Sacramento, California, United States

HMD Research, LLC; 🇺🇸 Orlando, Florida, United States

Lowcountry Lung and Critical Care, P.A.; 🇺🇸 Charleston, South Carolina, United States

Florida Institute for Clinical Research; 🇺🇸 Orlando, Florida, United States

Clinical Research of Rock Hill; 🇺🇸 Rock Hill, South Carolina, United States