Clinical trial NCT03116971: Phase Ib/II Study of M3814 With Etoposide and Cisplatin in Small Cell Lung Cancer (SCLC) Extensive Disease (ED)
Official title: A Multicenter Study With an Open Label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and PK of M3814 in Combination With Etoposide and Cisplatin in Subjects With Treatment-naïve Small Cell Lung Cancer (SCLC) Extensive Disease (ED)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Keywords: M3814, Small Cell Lung Cancer (SCLC), Deoxyribonucleic acid-dependent protein kinase inhibitor, Chemotherapy
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2017-04-17
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: M3814 is an investigational drug under evaluation for treatment of lung cancer. The purpose of the study was to assess the Safety and Efficacy of M3814 in combination with chemotherapy with SCLC ED.

Detailed description: The study was intended to be a phase I/II trial, but the study never moved forward to Phase II due to recruitment challenges.

Eligibility criteria: Inclusion Criteria:

To be eligible for the study (Phase Ib and Phase II) the participant must fulfill all of the following criteria:

* Male or female participants at least 18 years of age
* Histological or cytological diagnosis of SCLC
* Extensive disease (ie, disease beyond ipsilateral hemithorax, which may include malignant pleural or pericardial effusion or hematogenous metastases \[Tany, Nany, M1a/b; T3-T4, Nany, M0, due to multiple lung nodules or extent of disease that precludes a tolerable radiation field, as judged by the Investigator\])
* Participants eligible for first line platinum-based chemotherapy
* Measurable or evaluable disease according to RECIST v1.1
* Eastern Cooperative Oncology Group performance status (ECOG PS) less than equals to (\<=) 2
* Life expectancy of greater than equals to (≥) 3 months
* Female participants of childbearing potential and male participants with female partners of childbearing potential must be willing to avoid pregnancy Note: Other protocol defined criteria could apply.

Exclusion Criteria:

Participants are not eligible for the study if they fulfill any of the following exclusion criteria:

* Prior anticancer therapy for extensive disease (ED) SCLC including experimental agents.
* Concurrent use of other anticancer therapy including any investigational agent within 28 days prior to the first dose of the investigational drug M3814.
* Extensive prior radiotherapy (RT) on more than 30% of bone marrow reserves (by Investigator judgment)
* Prior bone marrow/stem cell transplantation within 5 years before study start (Phase II only)
* Major surgical intervention within 28 days prior to the first dose of investigational drug administration. Intervention(s) to establish the diagnosis for SCLC is permitted within 28 days as long as participants are cleared by the medical and surgical teams.
* Poor vital organ functions defined as:
* Bone marrow impairment as evidenced by hemoglobin less than (\<) 9.0 gram per deci liter (g/dL) (5.7 micromole per liter (μmol/L)), absolute neutrophil count \< 1.5 × 109/L, platelets \< 100 × 109/L
* Renal impairment as evidenced by calculated creatinine clearance \< 60 mL/minutes (min) (according to the Cockcroft-Gault formula)
* Liver function abnormality as defined by total bilirubin greater than (\>) 1.5 × upper limit of normal (ULN) or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2.5 × ULN (participants with liver involvement: a maximum of AST/ALT 5 × ULN)
* Contraindication to the use of etoposide or cisplatin
* Participants currently receiving (or unable to stop using prior to receiving the first dose of investigational drug) medications or herbal supplements known to be potent inhibitors of cytochrome P450 (CYP) 3A and CYP2C19 (unless treatment can be discontinued at least 1 week prior to receiving the first dose of investigational drug) or potent inducers of CYP3A and CYP2C19 (unless treatment can be discontinued at least 3 weeks prior to receiving the first dose of investigational drug). Note: Other protocol defined criteria could apply.

Primary outcomes:
measure: Phase Ib: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period.
timeFrame: up to 21 days
measure: Phase Ib: Determination of Recommended Phase II dose (RP2D) of Escalating Dose of M3814 in Combination With Cisplatin and Etoposide for the Phase II Part of the Study
timeFrame: up to 11 months
measure: Phase II: Progression Free Survival (PFS) as Assessed by the Investigator according to RECIST v1.1
timeFrame: Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 24 months
Secondary outcomes:
measure: Phase Ib: Number of Subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths
timeFrame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
measure: Phase Ib: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs)
timeFrame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
measure: Phase Ib: Change in Eastern Cooperative Oncology Group performance status (ECOG PS)
timeFrame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
measure: Phase Ib: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1
timeFrame: Post randomization with period tumor evaluations until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy, assessed up to 11 months
measure: Phase Ib: Duration of Response (DoR) According to RECIST v1.1
timeFrame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months
measure: Phase Ib: Percentage of Subjects With Disease Control
timeFrame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months
measure: Phase Ib: Progression Free Survival (PFS) According to RECIST v1.1
timeFrame: Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 11 months
measure: Phase Ib: Overall Survival (OS)
timeFrame: Time from randomization to death due to any cause, assessed up to 11 months
measure: Phase Ib: Area under the concentration-time curve from 0 to 4 hours (AUC 0-4), 0 to 24 hours (AUC 0-24) for M3814, Cisplatin and Etoposide
timeFrame: Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose, C3D1 Pre-dose and 3.5 hrs post dose
measure: Phase Ib: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide
timeFrame: Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase Ib: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose
measure: Phase Ib: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose
measure: Phase Ib: Apparent Terminal Half-life (t1/2) for M3814
timeFrame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose
measure: Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814
timeFrame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose
measure: Phase Ib: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose
measure: Phase Ib: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hr post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase Ib: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase Ib: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase Ib: Terminal rate constant (λz) for M3814, Cisplatin and Etoposide
timeFrame: Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase Ib: Changes in Cmax for M3814 Between Day -1 and C2D1
timeFrame: Day (D) -1, Cycle (C) 2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
measure: Phase Ib: Changes in AUC for M3814 Between Day -1 and C2D1
timeFrame: Day (D) -1, Cycle (C) 2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
measure: Phase Ib: Changes in AUC for Etoposide From C1D1 to C1D2, C1D3, and C2D1 (for the first 2 dose levels), or From C1D1 to C2D1 (other dose levels)
timeFrame: Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
measure: Phase Ib: Changes in Cmax for Etoposide From C1D1 and C2D1
timeFrame: Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
measure: Phase Ib: Changes in AUC for Cisplatin From C1D1 to C1D2, C1D3, and C2D1 (for the first 2 dose levels), or From C1D1 to C2D1 (other dose levels)
timeFrame: Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
measure: Phase Ib: Changes in Cmax for Cisplatin From C1D1 and C2D1
timeFrame: Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose
measure: Phase II: Overall Survival (OS)
timeFrame: Time from randomization to death due to any cause, assessed up to 24 months
measure: Phase II: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1
timeFrame: Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
measure: Phase II: Duration of Response (DoR) According to RECIST v1.1
timeFrame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months
measure: Phase II: Percentage of Subjects With Disease Control
timeFrame: First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months
measure: Phase II: Percentage of Subjects Who Received Prophylactic Cranial Irradiation (PCI) and/or Thorax Irradiation After 6 Cycles of Treatment
timeFrame: After 6 Cycles of treatment, assessed up to 24 months
measure: Phase II: Tumor shrinkage From Baseline in target lesions
timeFrame: Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
measure: Phase II: Number of subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths
timeFrame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
measure: Phase II: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs)
timeFrame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
measure: Phase II: Change in Eastern Cooperative Oncology Group performance status (ECOG PS)
timeFrame: From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment
measure: Phase II: Primary Health-Related Quality of Life (HRQoL) Based on Time to Definitive Deterioration (TUDD) as Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)
timeFrame: Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
measure: Phase II: Primary HRQoL based on TUDD Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)
timeFrame: Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
measure: Phase II: Primary HRQoL based on TUDD Assessed Using European Quality of Life 5- dimensions questionnaire (EQ-5D)
timeFrame: Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months
measure: Phase II: Area under the concentration-time curve from 0 to 24 hours (AUC 0-24) for M3814, Cisplatin and Etoposide
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Apparent Terminal Half-life (t1/2) for M3814
timeFrame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose
measure: Phase II: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814
timeFrame: C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose
measure: Phase II: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide
timeFrame: Time Frame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
measure: Phase II: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide
timeFrame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Research site
state: Arizona
city: Santa Rosa
country: United States
facility: Research site 1
state: California
city: Santa Rosa
country: United States
facility: Research site
state: California
city: Whittier
country: United States
facility: Research site
state: California
city: Danbury
country: United States
facility: Research site
state: Connecticut
city: Norwalk
country: United States
facility: Research site
state: Connecticut
city: Columbus
country: United States
facility: Research site
state: Georgia
city: Newnan
country: United States
facility: Research site
state: Georgia
city: Topeka
country: United States
facility: Research site
state: Kansas
city: Ashland
country: United States
facility: Research site
state: Kentucky
city: Billings
country: United States
facility: Research site
state: Montana
city: Pinehurst
country: United States
facility: Research site
state: North Carolina
city: Cincinnati
country: United States
facility: Research site
state: Ohio
city: Portland
country: United States
facility: Research site
state: Oregon
city: Philadelphia
country: United States
facility: Research site
state: Pennsylvania
city: Houston
country: United States
facility: Research site
state: Texas
city: Aalst
country: Belgium
facility: Research site
city: Charleroi
country: Belgium
facility: Research site
city: Edegem
country: Belgium
facility: Research site
city: Gent
country: Belgium
facility: Research site
city: Libramont
country: Belgium
facility: Research site
city: Liège
country: Belgium
facility: Research site
city: Roeselare
country: Belgium
facility: Research site
city: Yvoir
country: Belgium
facility: Research site
city: Sofia
country: Bulgaria
facility: Research site 4
city: Sofia
country: Bulgaria
facility: Research site 2
city: Sofia
country: Bulgaria
facility: Research site 6
city: Sofia
country: Bulgaria
facility: Reasearch site 5
city: Sofia
country: Bulgaria
facility: Research site 3
city: Sofia
country: Bulgaria
facility: Research site 1
city: Calgary
country: Canada
facility: Research site
state: Alberta
city: St. John
country: Canada
facility: Research site
state: New Brunswick
city: London
country: Canada
facility: Research site
state: Ontario
city: Toronto
country: Canada
facility: Research site
state: Ontario
city: Benesov
country: Czechia
facility: Research site
city: Olomouc
country: Czechia
facility: Research site
city: Aalborg
country: Denmark
facility: Research site
city: Herlev
country: Denmark
facility: Research site
city: Odense C
country: Denmark
facility: Research site
city: Freiburg
country: Germany
facility: Research site
state: Baden Wuerttemberg
city: Gauting
country: Germany
facility: Research site
state: Bavaria
city: Nuernberg
country: Germany
facility: Research site
state: Bavaria
city: Hannover
country: Germany
facility: Research site
state: Lower Saxony
city: Chemnitz
country: Germany
facility: Research site
state: Saxony
city: Kiel
country: Germany
facility: Research site
state: Schleswig-Holstein
city: Luebeck
country: Germany
facility: Research site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Research site 1
city: Berlin
country: Germany
facility: Research site 2
city: Budapest
country: Hungary
facility: Research site 1
city: Budapest
country: Hungary
facility: Research site 2
city: Budapest
country: Hungary
facility: Research site 3
city: Farkasgyepu
country: Hungary
facility: Research site
city: Szekszard
country: Hungary
facility: Research site
city: Szolnok
country: Hungary
facility: Research site
city: Rozzano
country: Italy
facility: Research site
state: Milano
city: Catania
country: Italy
facility: Research site
city: Genova
country: Italy
facility: Research site
city: Napoli
country: Italy
facility: Research site
city: Ravenna
country: Italy
facility: Research site
city: Reggio Emilia
country: Italy
facility: Research site
city: Roma
country: Italy
facility: Research site
city: Torino
country: Italy
facility: Research site
city: Olsztyn
country: Poland
facility: Research site
city: Poznan
country: Poland
facility: Research site
city: Warszawa
country: Poland
facility: Research site
city: Wodzislaw Slaski
country: Poland
facility: Research site
city: Baia Mare
country: Romania
facility: Research site
city: Cluj-Napoca
country: Romania
facility: Research site
city: Cluj-Napoca
country: Romania
facility: Research site
city: Craiova
country: Romania
facility: Research site
city: Timisoara
country: Romania
facility: Research site
city: Badajoz
country: Spain
facility: Research site
city: Madrid
country: Spain
facility: Research site 1
city: Madrid
country: Spain
facility: Research site 4
city: Madrid
country: Spain
facility: Research site 3
city: Madrid
country: Spain
facility: Research site 2
city: Hull
country: United Kingdom
facility: Research site
state: East Riding Of Yorkshire
city: London
country: United Kingdom
facility: Research site
state: Greater London
city: Sheffield
country: United Kingdom
facility: Research site
state: South Yorkshire
city: Glasgow
country: United Kingdom
facility: Research site
state: Strathclyde
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: