A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH. (CHEST-1)

Randomized, Double-blind, Placebo-controlled, Multi-centre, Multi-national Study to Evaluate the Efficacy and Safety of Oral BAY63-2521 (1 mg, 1.5 mg, 2 mg, or 2.5 mg Tid) in Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521, given orally for 16 weeks, in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Riociguat (Adempas, BAY63-2521); Drug: Placebo

Detailed Description

Adverse event data will be covered in Adverse events section.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Corrientes, Argentina, 3400
• Australia
  • Victoria
    • Prahran, Victoria, Australia, 3181
• Austria
  • Innsbruck, Austria, 6020
  • Wien, Austria, 1090
• Belgium
  • Bruxelles - Brussel, Belgium, 1070
  • Leuven, Belgium, 3000
• Brazil
  • Rio de Janeiro, Brazil, 21941-913
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020 090
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 04020-050
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
  • Ontario
    • London, Ontario, Canada, N6A 4G5
    • Ottawa, Ontario, Canada, K1Y 4W7
    • Toronto, Ontario, Canada, M5G 2N2
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
• China
  • Beijing, China, 100020
  • Beijing, China, 100037
  • Beijing, China, 100038
  • Shanghai, China, 200433
  • Shandong
    • Qingdao, Shandong, China, 266003
• Czechia
  • Praha 2, Czechia, 12808
    • Všeobecná fakultní nemocnice
• Denmark
  • Aarhus N, Denmark, 8200
• France
  • Brest, France, F-29609
  • Caen, France, 14033
  • Clamart Cedex, France, 92141
    • Hôpital Antoine Béclère
  • Lille Cedex, France, 59037
  • Nice, France, 06200
  • Pessac, France, 33604
  • Rouen, France, 76031
  • Vandoeuvre Les Nancy, France, F-54500
• Germany
  • Hamburg, Germany, 20251
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
    • Heidelberg, Baden-Württemberg, Germany, 69126
  • Bayern
    • München, Bayern, Germany, 81377
    • Würzburg, Bayern, Germany, 97074
  • Hessen
    • Gießen, Hessen, Germany, 35392
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50924
  • Saarland
    • Homburg, Saarland, Germany, 66421
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
    • Leipzig, Sachsen, Germany, 04103
• Italy
  • Lombardia
    • Pavia, Lombardia, Italy, 27100
• Japan
  • Chiba, Japan, 260-8677
  • Fukuoka, Japan, 812-8582
  • Aichi
    • Nagoya, Aichi, Japan, 467-8602
    • Seto, Aichi, Japan, 489-8642
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8555
  • Ishikawa
    • Komatsu, Ishikawa, Japan, 923-8560
  • Kanagawa
    • Fujisawa, Kanagawa, Japan, 251-0041
    • Kawasaki, Kanagawa, Japan, 216-8511
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
  • Nagano
    • Suwa, Nagano, Japan, 392-8510
  • Osaka
    • Suita, Osaka, Japan, 565-8565
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Mitaka, Tokyo, Japan, 181-8611
    • Shinjuku-ku, Tokyo, Japan, 162-8655
    • Shinjuku-ku, Tokyo, Japan, 160-8582
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 06351
• Mexico
  • Mexico D.F., Mexico, 14080
  • Querétaro, Mexico, 38000
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
    • Monterrey, Nuevo Leon, Mexico, 64020
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
• Poland
  • Krakow, Poland, 31-202
  • Otwock, Poland, 05-400
• Portugal
  • Coimbra, Portugal, 3000-075
• Russian Federation
  • Novosibirsk, Russian Federation, 630055
  • St. Petersburg, Russian Federation, 197341
• Slovakia
  • Bratislava 37, Slovakia, 833 48
• Spain
  • Barcelona, Spain, 08036
  • Madrid, Spain, 28041
• Switzerland
  • Zürich, Switzerland, 8091
• Taiwan
  • Taipei, Taiwan, 100
• Turkey
  • Ankara, Turkey
  • Istanbul, Turkey, 34093
  • Izmir, Turkey, 35040
• United Kingdom
  • London, United Kingdom, W12 0HS
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
  • West Dunbartonshire
    • Glasgow, West Dunbartonshire, United Kingdom, G81 4DY
• United States
  • California
    • La Jolla, California, United States, 92093
    • Sacramento, California, United States, 95817
  • Florida
    • Miami, Florida, United States, 33136
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Maryland
    • Baltimore, Maryland, United States, 21205
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
  • Ohio
    • Cleveland, Ohio, United States, 44195
    • Columbus, Ohio, United States, 43221
  • Texas
    • Dallas, Texas, United States, 75390

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patients with CTEPH either inoperable or with persistent or recurrent PH after surgery.

Exclusion Criteria:

• All types of pulmonary hypertension except subtypes 4.1 and 4.2 of the Venice Clinical Classification of Pulmonary Hypertension.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Riociguat (Adempas, BAY63-2521)_individual dose titration; Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks	Drug: Riociguat (Adempas, BAY63-2521); BAY63-2521: 1 mg tid - 2,5 mg tid orally for 16 weeks.
Placebo Comparator: Placebo; Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks	Drug: Placebo; Matching Placebo tid orally for 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16	6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.	Baseline and week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16	The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80*(PAPmean - PCWP)/CO	Baseline and week 16
N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16	N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.	Baseline and week 16
World Health Organization (WHO) Functional Class - Change From Baseline to Week 16	The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH.	Baseline and week 16
Percentage of Participants With Clinical Worsening	The combined endpoint "time to clinical worsening", made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; rescue endarterectomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH.	At week 16
Borg CR 10 Scale - Change From Baseline to Week 16	The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal").	Baseline and week 16
EQ-5D Utility Score - Change From Baseline to Week 16	EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).	Baseline and week 16
Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16	The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst).	Baseline and week 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Caused Mortality	All cause mortality (including cardiovascular mortality) was one component of the composite endpoint "time to clinical worsening".	At visit 6 (week 16)
Mean Pulmonary Artery Pressure (PAPmean) - Change From Baseline to Week 16	Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.	Baseline and week 16
Cardiac Index (CI) - Change From Baseline to Week 16	The cardiac index (CI) is a calculated hemodynamic parameter. CI is derived from the directly measured parameters cardiac output (CO), divided by the body surface area (BSA). BSA is a calculated parameter, using the subject's height and weight in the DuBois formula. Formula: BSA = (W [kg]*0.425)*(H [cm]*0.725)*0.007184 (m^2)	Baseline and week 16
Systolic Blood Pressure (SBP) - Change From Baseline to Week 16	Systolic systemic arterial blood pressure (SBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 95 - 180 mmHg.	Baseline and week 16
Diastolic Blood Pressure (DBP) - Change From Baseline to Week 16	Diastolic systemic arterial blood pressure (DBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: <= 110 mmHg.	Baseline and week 16
Heart Rate (HR) - Change From Baseline to Week 16	Heart rate (HR) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 50 -105 beats per minute (bpm) at rest.	Baseline and week 16
Alanine Aminotransferase (ALT) - Change From Baseline to Week 16	Alanine Aminotransferase (ALT) is a standard clinical chemistry parameter. Normal range: 0 to 45 U/L.	Baseline and week 16
Aspartate Aminotransferase (AST) - Change From Baseline to Week 16	Aspartate Aminotransferase (AST) is a standard clinical chemistry parameter. Normal range: 0 to 41 U/L.	Baseline and week 16
Alkaline Phosphatase (AP) - Change From Baseline to Week 16	Alkaline phosphatase (AP) is a standard clinical chemistry parameter. Normal range: 40 to 129 U/L (males), 35 to 104 U/L (females)	Baseline and week 16
Bilirubin - Change From Baseline to Week 16	Bilirubin is a standard clinical chemistry parameter. Normal range: 0.1 to 1.2 mg/dL	Baseline and week 16
Creatinine - Change From Baseline to Week 16	Creatinine is a standard clinical chemistry parameter. Normal range: 0.25 to 1.20 mg/dL (males), 0.46 to 1.00 mg/dL (females)	Baseline and week 16
Creatinine Clearance - Change From Baseline to Week 16	Creatinine clearance is a standard clinical chemistry parameter. Normal range: 90 to 140 mL/min (males), 80 to 125 mL/min (females)	Baseline and week 16
Creatine Kinase (CK) - Change From Baseline to Week 16	Creatine Kinase is a standard clinical chemistry parameter. Normal range: 35 to 232 U/L (males), 26 to 145 U/L (females)	Baseline and week 16
Erythrocytes (RBC) - Change From Baseline to Week 16	Erythrocytes (red blood cells, RBC) is a standard clinical hematology parameter. Normal range: 4.6 to 5.8*10^12 cells/L (males), 4.1 to 5.2*10^12 cells/L (females)	Baseline and week 16
Leukocytes (WBC) - Change From Baseline to Week 16	Leukocytes (white blood cells, WBC) is a standard clinical hematology parameter. Normal range: 4.0 to 10.7*10^9 cells/L	Baseline and week 16
Lymphocytes - Change From Baseline to Week 16	Total lymphocytes is a standard clinical hematology parameter. Normal range: 1.0 to 4.0*10^9 cells/L	Baseline and week 16
Neutrophils - Change From Baseline to Week 16	Neutrophils is a standard clinical hematology parameter. Normal range: 1.6 to 7.4*10^9 cells/L	Baseline and week 16
Hemoglobin - Change From Baseline to Week 16	Hemoglobin is a standard clinical hematology parameter. Normal range: 13.5 to 17.5 g/dL (males), 12.0 to 16.0 g/dL (females)	Baseline and week 16
Hematocrit - Change From Baseline to Week 16	Hematocrit is a standard clinical hematology parameter. Normal range: 40 to 52% (males), 36 to 46% (females)	Baseline and week 16
Potassium - Change From Baseline to Week 16	Potassium is a standard clinical chemistry parameter. Normal range: 3.5 to 5.3 mmol/L	Baseline and week 16
Urate - Change From Baseline to Week 16	Urate is a standard clinical chemistry parameter. Normal range: 4.0 to 8.5 mg/dL (males, 16-59 years), 3.4 to 8.7 mg/dL (males, >60 years) 2.5 to 7.5 mg/dL (females)	Baseline and week 16
Urea (BUN) - Change From Baseline to Week 16	Urea (blood urea nitrogen, BUN) is a standard clinical chemistry parameter. Normal range: 4 to 25 mg/dL	Baseline and week 16
Cystatin C - Change From Baseline to Week 16	Cystatin C is a biomarker. Normal range: 0.53 to 1.01 ng/mL	Baseline and week 16
Triacylglycerol Lipase - Change From Baseline to Week 16	Triacylglycerol lipase is a standard clinical chemistry parameter. Normal range: 7 to 60 U/L	Baseline and week 16
Arterial Partial Pressure of Carbon Dioxide (PaCO2) - Change From Baseline to Week 16	Arterial partial pressure of carbon dioxide (PaCO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.	Baseline and week 16
Arterial Partial Oxygen Pressure (PaO2) - Change From Baseline to Week 16	Arterial partial pressure of oxygen (PaO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.	Baseline and week 16
Oxygen Saturation (SaO2) - Change From Baseline to Week 16	Oxygen saturation (SaO2) is measured as part of the capillary or arterial blood gas analysis. Normal blood oxygen saturation is considered 95-100 percent. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.	Baseline and week 16
Mean PR Duration (PRmean) - Change From Baseline to Week 16	PR duration was evaluated as part of the 12-lead electrocardiogram. electrocardiograms (ECGs) were recorded after the participant had been at rest for 15 minutes in a supine position.	Baseline and week 16
Mean QRS Duration (QRSmean) - Change From Baseline to Week 16	QRS duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.	Baseline and week 16
Mean QT Duration (QTmean) - Change From Baseline to Week 16	QT duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.	Baseline and week 16
Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Week 16	Bazett-corrected QTcB duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.	Baseline and week 16
Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Week 16	Fridericia-corrected QTcF duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.	Baseline and week 16
Mean RR Duration (RRmean) - Change From Baseline to Week 16	RR duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.	Baseline and week 16
Mean Ventricular Rate (VRmean) - Change From Baseline to Week 16	Ventricular rate was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position	Baseline and week 16

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Archer SL. Riociguat for pulmonary hypertension--a glass half full. N Engl J Med. 2013 Jul 25;369(4):386-8. doi: 10.1056/NEJMe1306684. No abstract available.
• Wang C, Jing ZC, Huang YG, Zhou DX, Liu ZH, Meier C, Nikkho S, Curram J, Zhang P, He JG. Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison. Heart Asia. 2016 May 17;8(1):74-82. doi: 10.1136/heartasia-2015-010712. eCollection 2016.
• Ghofrani HA, Humbert M, Langleben D, Schermuly R, Stasch JP, Wilkins MR, Klinger JR. Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension. Chest. 2017 Feb;151(2):468-480. doi: 10.1016/j.chest.2016.05.024. Epub 2016 Jun 2.
• Saleh S, Becker C, Frey R, Muck W. Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulm Circ. 2016 Mar;6(Suppl 1):S86-96. doi: 10.1086/685404.
• Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013 Jul 25;369(4):319-29. doi: 10.1056/NEJMoa1209657.
• Simonneau G, D'Armini AM, Ghofrani HA, Grimminger F, Jansa P, Kim NH, Mayer E, Pulido T, Wang C, Colorado P, Fritsch A, Meier C, Nikkho S, Hoeper MM. Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016 May;4(5):372-80. doi: 10.1016/S2213-2600(16)30022-4. Epub 2016 Apr 8.
• Kim DY, Kim HJ, Han KH, Han SY, Heo J, Woo HY, Um SH, Kim YH, Kweon YO, Lim HY, Yoon JH, Lee WS, Lee BS, Lee HC, Ryoo BY, Yoon SK. Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data. Cancer Res Treat. 2016 Oct;48(4):1243-1252. doi: 10.4143/crt.2015.278. Epub 2016 Feb 24.
• Kudo M, Ikeda M, Takayama T, Numata K, Izumi N, Furuse J, Okusaka T, Kadoya M, Yamashita S, Ito Y, Kokudo N. Safety and efficacy of sorafenib in Japanese patients with hepatocellular carcinoma in clinical practice: a subgroup analysis of GIDEON. J Gastroenterol. 2016 Dec;51(12):1150-1160. doi: 10.1007/s00535-016-1204-2. Epub 2016 Apr 22.
• Benza RL, Boucly A, Farber HW, Frost AE, Ghofrani HA, Hoeper MM, Lambelet M, Rahner C, Bansilal S, Nikkho S, Meier C, Sitbon O. Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study. J Heart Lung Transplant. 2022 Mar;41(3):411-420. doi: 10.1016/j.healun.2021.10.013. Epub 2021 Oct 28.
• Benza RL, Farber HW, Frost AE, Ghofrani HA, Corris PA, Lambelet M, Nikkho S, Meier C, Hoeper MM. Application of the REVEAL risk score calculator 2.0 in the CHEST study. Respir Med. 2022 Apr-May;195:106783. doi: 10.1016/j.rmed.2022.106783. Epub 2022 Mar 1.
• Kim NH, D'Armini AM, Grimminger F, Grunig E, Hoeper MM, Jansa P, Mayer E, Neurohr C, Simonneau G, Torbicki A, Wang C, Fritsch A, Davie N, Ghofrani HA. Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension. Heart. 2017 Apr;103(8):599-606. doi: 10.1136/heartjnl-2016-309621. Epub 2016 Dec 23.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2009
• Primary Completion (Actual): June 27, 2012
• Study Completion (Actual): June 27, 2012

Study Registration Dates

• First Submitted: December 15, 2008
• First Submitted That Met QC Criteria: March 3, 2009
• First Posted (Estimated): March 4, 2009

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: PH; Chronic thromboembolic pulmonary hypertension; soluble Guanylate Cyclase Stimulator; sGC
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Enzyme Activators; Riociguat
• Other Study ID Numbers: 11348; 2007-000072-16 (EudraCT Number)