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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02138825




Registration number
NCT02138825
Ethics application status
Date submitted
15/04/2014
Date registered
15/05/2014
Date last updated
4/12/2017

Titles & IDs
Public title
Efficacy and Safety of Riociguat in Patients With Symptomatic Pulmonary Hypertension (PH) Associated With Idiopathic Interstitial Pneumonias (IIP)
Scientific title
A Randomized, Double-blind, Placebo-controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat (0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID) in Patients With Symptomatic Pulmonary Hypertension Associated With Idiopathic Interstitial Pneumonias (IIP).
Secondary ID [1] 0 0
2010-024332-42
Secondary ID [2] 0 0
13605
Universal Trial Number (UTN)
Trial acronym
RISE-IIP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Interstitial Pneumonias / Hypertension,Pulmonary 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Placebo

Experimental: Riociguat (Adempas, BAY63-2521) - In the main study treatment phase participants received Riociguat titrated to optimal dose within range of 0.5 mg TID (3 times a day) to 2.5 mg TID for 10 weeks followed by maintenance period of 16 weeks. This phase was followed by a long-term extension phase, which included a blinded sham titration phase of 10 weeks followed by an open-label extension phase. During the open-label extension phase participants were to be treated with Riociguat until commercial access in the indication of pulmonary hypertension (PH) associated with idiopathic interstitial pneumonias (IIP) or until an agreed time point is defined with the individual country, local regulatory authority and the Sponsor's global team.

Placebo Comparator: Placebo - In the main study treatment phase participants received sham titration within range of 0.5 mg TID to 2.5 mg TID for 10 weeks followed by maintenance period of 16 weeks. This phase was followed by a long-term extension phase, which included a blinded titration phase to optimal dose of Riociguat of 10 weeks followed by an open-label extension phase. During the open-label extension phase participants were to be treated with Riociguat until commercial access in the indication of PH associated with IIP or until an agreed time point is defined with the individual country, local regulatory authority and the Sponsor's global team.


Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
Active drug 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration. The starting dose will be 0.5 mg TID, and the dose will be adjusted every two weeks for ten weeks in 0.5 mg increments up to a maximum dose of 2.5 mg TID based on patient's systolic blood pressure and well-being.

Treatment: Drugs: Placebo
Inactive dosed at 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration for 26 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change in 6 Minute Walking Distance (6MWD) From Baseline to Week 26
Timepoint [1] 0 0
Baseline to 26 weeks
Secondary outcome [1] 0 0
Number of Participants With Clinical Worsening
Timepoint [1] 0 0
From baseline to week 26

Eligibility
Key inclusion criteria
-

- Men or women aged from =18 to =80 years

- Diagnosed with one of the following (confirmed using a multidisciplinary approach, as
per ATS(American Thoracic Society) / ERS(European Respiratory Society) / JRS (Japanese
Respiratory Society) / ALAT(Latin American Thoracic Association) guidelines:

- Major IIPs (idiopathic interstitial pneumonias) diagnosis or suspected as one of
the following:

- Idiopathic pulmonary fibrosis

- Idiopathic nonspecific interstitial pneumonia

- Respiratory bronchiolitis-interstitial lung disease

- Desquamative interstitial pneumonia

- Cryptogenic organizing pneumonia

- Acute interstitial pneumonia

- Rare IIPs diagnosis by one of the following:

- Idiopathic lymphoid interstitial pneumonia

- Idiopathic pleuroparenchymal fibroelastosis

- Unclassifiable idiopathic interstitial pneumonias

- Forced Vital Capacity (FVC) = 45 %

- 6MWD (6 minutes walking distance) = 150 m to = 450 m {under stable O2(oxygen)
supplementation via nasal cannula}

- Diagnosis of PH (pulmonary hypertension) confirmed by right heart catheter (RHC) with
(mean artery pulmonary artery pressure )mPAP = 25 mmHg and (pulmonary artery wedge
pressure)PAWP =15 mmHg at rest

- Systolic blood pressure (SBP) = 95 mmHg and no signs or symptoms of hypotension

- WHO functional class II-IV

- Women of childbearing potential can only be included in the study if a pregnancy test
is negative. Women of childbearing potential must agree to use adequate contraception
when sexually active. 'Adequate contraception' is defined as any combination of at
least 2 effective methods of birth control, of which at least one is a physical
barrier (e.g. condoms with hormonal contraception or implants or combined oral
contraceptives, certain intrauterine devices). Adequate contraception is required from
the signing of the informed consent form up until 4 weeks after the last study drug
administration

-
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known significant left heart disease:

- Pulmonary venous hypertension indicated by baseline pulmonary capillary wedge
pressure > 15 mmHg

- Symptomatic coronary artery disease

- Systolic left-ventricular dysfunction with an left ventricular ejection fraction
(LVEF) <45%

- Active state of hemoptysis or pulmonary hemorrhage, including those events managed by
bronchial artery embolization

- Any history of bronchial artery embolization or massive hemoptysis within 3 months
prior to screening. Massive hemoptysis being defined as acute bleeding >240 mL in a
24-hour period or recurrent bleeding >100 mL/d over several days

- Difference > 15% between the eligibility and the baseline 6MWD test

- Forced expiratory volume in one second (FEV1) / Forced Vital Capacity (FVC) <0.65
after bronchodilator administration

- Initiation in cytotoxic, immunosuppressive, cytokine modulating therapy initiated
within 3 months prior to screening. Such agents might include. azathioprine,
cyclophosphamide, corticosteroids, etanercept, tumor necrosis factor alpha (TNFa)
inhibitors and others

- Any specific treatment for (pulmonary arterial hypertension) PAH/PH (pulmonary
hypertension )within 3 months prior to screening

- Concomitant use of the following medication: nitrates or (nitric oxide) NO donors
(such as amyl nitrite) in any form, phosphodiesterase 5 inhibitors (such as
sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors
(theophylline, dipyridamole),

- Pregnant women (i.e. positive pregnancy test or other signs of pregnancy), or breast
feeding women, or women of childbearing potential not using adequate contraception (as
defined in the aforementioned inclusion criterion) and not willing to agree to 4
weekly pregnancy testing from Visit 1(first administration of study drug) onwards
until 4 weeks after last study drug intake

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/09/2016
Sample size
Target
Accrual to date
Final
147
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Darlinghurst
Recruitment hospital [3] 0 0
- Sydney
Recruitment hospital [4] 0 0
- Chermside
Recruitment hospital [5] 0 0
- Adelaide
Recruitment hospital [6] 0 0
- Prahran
Recruitment hospital [7] 0 0
- Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2751 - Sydney
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3181 - Prahran
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Colorado
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Florida
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Kansas
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United States of America
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Kentucky
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New York
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United States of America
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Tennessee
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Ciudad Auton. de Buenos Aires
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Argentina
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Mendoza
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Argentina
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Tucuman
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Belgium
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Leuven
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Colombia
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Distrito Capital de Bogotá
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Colombia
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Santander
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Colombia
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Valle del Cauca
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Colombia
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Bogotá
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Colombia
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Santafe de Bogotá
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Denmark
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Aarhus N
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France
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Bron
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France
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Lille Cedex
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France
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Marseille
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France
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Paris Cedex 15
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Sachsen
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Germany
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Grosshansdorf
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Greece
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Athens
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Greece
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Haidari
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Greece
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Ioannina
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Greece
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Thessaloniki
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Italy
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Emilia-Romagna
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Sicilia
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Italy
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Toscana
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Japan
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Aichi
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Japan
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Kanagawa
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Osaka
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Tokyo
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Chiba
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Auckland
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Christchurch
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Portugal
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Coimbra
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Portugal
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Porto
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Portugal
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Vila Nova de Gaia
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Russian Federation
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Vladimir
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Saudi Arabia
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Riyadh
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Spain
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Barcelona
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Valencia
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Switzerland
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Bern
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Switzerland
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Genève
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Switzerland
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Zürich
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Turkey
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Denizli
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Turkey
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Izmir
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United Kingdom
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Cambridgeshire
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West Dunbartonshire
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United Kingdom
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London
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United Kingdom
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Newcastle

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the efficacy and safety of 26-weeks of treatment with riociguat vs. placebo in
patients with symptomatic PH (pulmonary hypertension) associated with IIP (idiopathic
interstitial pneumonias).
Trial website
https://clinicaltrials.gov/ct2/show/NCT02138825
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02138825