Cabazitaxel at 20 mg/m² Compared to 25 mg/m² With Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT01308580
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
- To demonstrate the non inferiority in term of overall survival (OS) of Cabazitaxel 20 mg/m² (Arm A) versus Cabazitaxel 25 mg/m² (Arm B) in combination with prednisone in participants with metastatic castration resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen.
Secondary Objectives:
* To evaluate safety in the 2 treatment arms and to assess if Cabazitaxel 20 mg/m² was better tolerated than Cabazitaxel 25 mg/m².
* To compare efficacy of Cabazitaxel at 20 mg/m² and 25 mg/m² for:
* Progression Free Survival (PFS) defined as the first occurrence of any of the following events: tumor progression per Response Evaluation Criteria In Solid Tumors (RECIST), prostate-specific antigen (PSA) progression, pain progression or death due to any cause;
* PSA Progression;
* Pain progression;
* Tumor response in participants with measurable disease (RECIST 1.1);
* PSA response;
* Pain response in participants with stable pain at baseline.
* To compare Health-related Quality of Life (HRQoL).
* To assess the pharmacokinetics and pharmacogenomics of Cabazitaxel.
- Detailed Description
Participants were treated until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles. All participants were followed when on study treatment and after completion of study treatment during follow up period until death or the study cutoff date, whichever came first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cabazitaxel 20 mg/m^2 Prednisone (or Prednisolone) Cabazitaxel 20 mg/m\^2 intravenous (IV) infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles. Cabazitaxel 20 mg/m^2 Cabazitaxel (XRP6258) Cabazitaxel 20 mg/m\^2 intravenous (IV) infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles. Cabazitaxel 25 mg/m^2 Cabazitaxel (XRP6258) Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles. Cabazitaxel 25 mg/m^2 Prednisone (or Prednisolone) Cabazitaxel 25 mg/m\^2 IV infusion over 1 hour on Day 1 of each 21-day cycle in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, unacceptable toxicity, participant's refusal of further study treatment or for a maximum of 10 cycles.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From baseline up to death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months) OS was defined as the time interval from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earlier of the last date the participant was known to be alive or the study cut-off date. The cut-off date for the final analysis of OS was the date when the 988th death had been observed. Analysis was performed by Kaplan-Meier method.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) From baseline up to tumor progression, PSA progression, pain progression, death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months) PFS was evaluated from date of randomization to date of first documentation of any of the events: 1) Radiological tumor progression: as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: at least a 20% increase in sum of diameters of target lesions (sum must also demonstrate an absolute increase of ≥5 mm) taking as reference the smallest sum while on study, appearance of one or more new lesions, or unequivocal progression of existing non target lesions, 2) Prostate Specific Antigen (PSA) progression: ≥25% increase over baseline/nadir value if baseline PSA ≥10 ng/mL; or 25% increase above the baseline level if baseline PSA \>0 ng/mL \& \<10 ng/mL; or post-baseline value of \>=2 ng/mL, if baseline PSA=0 ng/mL, 3) Pain progression: increase of ≥1 point in median Present Pain Intensity (PPI) from nadir or ≥25% increase in mean analgesic score (AS) from baseline score or requirement of local palliative radiotherapy, 4) Death. Analysis was performed by Kaplan-Meier method.
Time to Tumor Progression From baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months) Time to Tumor progression was defined as the first occurrence of radiological tumor progression according to RECIST 1.1. Radiological tumor progression was defined at least a 20% increase in sum of diameters of target lesions (sum must also demonstrate an absolute increase of ≥5 mm) taking as reference the smallest sum while on study, appearance of one or more new lesions, or unequivocal progression of existing non target-lesions. Analysis was performed by Kaplan-Meier method.
Percentage of Participants With Overall Objective Tumor Response From baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months) Overall objective tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1 criteria, as assessed by the investigator. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time to PSA Progression From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months) Time to PSA progression was time interval between randomization \& first occurrence of PSA progression. PSA progression defined as: 1) PSA responders (\>50% decline from baseline PSA ≥10 ng/mL): increase of ≥25% (≥2 ng/mL) over nadir value, confirmed by second PSA ≥3 weeks later; 2) PSA non-responders (did not achieve \>50% decline from baseline PSA ≥10 ng/mL): increase of ≥25% (≥2 ng/mL) over baseline value, confirmed by second PSA ≥3 weeks later; 3) In participants not eligible for PSA response (baseline PSA \<10 ng/mL): (a) participants with baseline PSA \>0 ng/mL \& \<10 ng/mL: increase in PSA by 25% (≥2 ng/mL) above baseline level, confirmed by second PSA value ≥3 weeks apart; (b) participants with baseline value=0 ng/mL: post-baseline PSA value ≥2 ng/mL. Note (for 1-3): Rise in PSA in first 12 weeks was progression only if met definition above and was associated with other sign of DP or if it continued beyond 12 weeks. Analysis was performed by Kaplan-Meier method.
Percentage of Participants With PSA Response From baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 48 months) PSA response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later in participants with baseline PSA value ≥10 ng/mL.
Time to Pain Progression From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months) Pain Progression was defined as an increase of ≥1 point in the median PPI from its nadir confirmed by a second assessment at least 3 weeks later or ≥25 % increase in the mean AS compared with the baseline score confirmed by a second assessment at least 3 weeks later or requirement for local palliative radiotherapy. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. AS was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was performed by Kaplan-Meier method.
Percentage of Participants With Pain Response From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months) Pain response was defined as either a ≥2-point decrease from baseline median PPI score without increase in AS, or a ≥50% decrease from baseline mean AS without increase in the PPI score, maintained for 2 consecutive evaluations at least 3 weeks apart. Increases in pain during the first 12 weeks were ignored in determining pain response.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of Health Related Quality of Life (HRQoL) Baseline, Day 1 of each Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 (each cycle 21-day); post-treatment follow up 1 (up to 12 weeks) FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P TOI combines physical well-being, functional well-being, and prostate-specific concerns sub-scales for a total possible score range of 0 to 104, where higher values represent better HRQoL.
Change From Baseline in FACT-P:Total Score as a Measure of HRQoL Baseline, Day 1 of each Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 (each cycle 21-day); post-treatment follow up 1 (up to 12 weeks) FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P Total Score sums all 5 sub-scales to give a score in the range of 0 to 156, where higher values represent better HRQoL.
Percentage of Participants With FACT-P Total Score Response From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months) FACT-P is a 39-item participant questionnaire that measures the concerns of participants with prostate cancer. It consists of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P Total Score sums all 5 sub-scales to give a score in the range of 0 to 156, where higher values represent better HRQoL. Responder of FACT-P was defined as at least one occurrence of 7-point improvement from baseline in FACT-P total score during treatment period.
Time to Definitive Deterioration of Score by 10% From Baseline on FACT-P Sub-Scales From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months) The time to definitive deterioration (10% decrease in score from baseline) was assessed for the individual sub-scales (Physical Well-Being; Social/Family Well-Being; Emotional Well-Being; Functional Well-Being; Prostate-Specific Concerns). Analysis was performed by Kaplan-Meier method.
Time to Definitive Deterioration of ECOG PS Score From Baseline From baseline until death or study cut-off date (maximum duration: 48 months) The ECOG PS was used to evaluate participant's DP and the effect of the disease on the participant's activities of daily living. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for \< 50 % of the time; 3= in bed for \> 50% of the time; 4= 100% bedridden; 5= dead). Time to definitive deterioration in ECOG PS score from baseline was defined as a change from 0, 1 to ≥2, or from 2 to ≥3. Analysis was performed by Kaplan-Meier method.
Time to Definitive Weight Loss by 5% and 10% From Baseline From baseline until death or study cut-off date (maximum duration: 48 months) Time to definitive weight loss was defined as the time to first occurrence of ≥5% or ≥10% decrease in body weight from baseline. Analysis was performed by Kaplan-Meier method.
Time to First Definitive Consumption of Narcotic Medication From baseline until DP, start of another anti-cancer therapy, death or study cut-off date (maximum duration: 48 months) Concomitant medications used were recorded for all participants, and time of first definitive consumption of narcotic medication (if it occurred) was determined. This measure summarizes the time from baseline to first definitive consumption of narcotic medication. Analysis was performed by Kaplan-Meier method.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From first administration of study treatment until 30 days after the last administration of study treatment (Maximum duration: 48 months) Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during on-treatment period. On-treatment period: The time from the first dose of treatment to 30 days after the last dose of treatment (either Cabazitaxel or Prednisone). A serious adverse event: Any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 4.03 (Grade 3 \[severe\] and Grade 4 \[life-threatening\]) was used in this study to grade clinical AEs.
Plasma Clearance (CL) for Cabazitaxel Day 1 of Cycle 1: 5 minutes before the end of infusion (EOI), 15 minutes, 1 to 4 hour, 6 to 24 hours, 48 to 168 hour after EOI Blood samples for pharmacokinetic (PK) analysis were obtained from a subset of the study participants (approximately 150 participants/group, by protocol) according to a sparse sampling strategy.
Plasma Steady State Volume of Distribution (Vss) for Cabazitaxel Day 1 of Cycle 1: 5 minutes before the EOI, 15 minutes, 1 to 4 hour, 6 to 24 hours, 48 to 168 hour after EOI Blood samples for PK analysis were obtained from a subset of the study participants (approximately 150 participants/group, by protocol) according to a sparse sampling strategy.
Trial Locations
- Locations (172)
Investigational Site Number 840014
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840021
🇺🇸Stamford, Connecticut, United States
Investigational Site Number 840020
🇺🇸Akron, Ohio, United States
Investigational Site Number 840012
🇺🇸Corpus Christi, Texas, United States
Investigational Site Number 056002
🇧🇪Bruxelles, Belgium
Investigational Site Number 056009
🇧🇪Charleroi, Belgium
Investigational Site Number 056016
🇧🇪Haine-Saint-Paul, Belgium
Investigational Site Number 528001
🇳🇱Zwolle, Netherlands
Investigational Site Number 604006
🇵🇪Lima, Peru
Investigational Site Number 604001
🇵🇪Lima, Peru
Investigational Site Number 642005
🇷🇴Alba Iulia, Romania
Investigational Site Number 642003
🇷🇴Cluj Napoca, Romania
Investigational Site Number 158002
🇨🇳Taiching, Taiwan
Investigational Site Number 788002
🇹🇳Tunis, Tunisia
Investigational Site Number 604002
🇵🇪Lima, Peru
Investigational Site Number 604004
🇵🇪Lima, Peru
Investigational Site Number 642002
🇷🇴Cluj Napoca, Romania
Investigational Site Number 642013
🇷🇴Onesti, Romania
Investigational Site Number 642007
🇷🇴Hunedoara, Romania
Investigational Site Number 642004
🇷🇴Cluj Napoca, Romania
Investigational Site Number 642012
🇷🇴Focsani, Romania
Investigational Site Number 158003
🇨🇳Tainan, Taiwan
Investigational Site Number 076003
🇧🇷Sao Jose Do Rio Preto, Brazil
Investigational Site Number 076001
🇧🇷Sao Paulo, Brazil
Investigational Site Number 076007
🇧🇷Salvador, Brazil
Investigational Site Number 076008
🇧🇷Sao Paulo, Brazil
Investigational Site Number 840002
🇺🇸Muscle Shoals, Alabama, United States
Investigational Site Number 840016
🇺🇸Lincoln, Nebraska, United States
Investigational Site Number 840007
🇺🇸New Orleans, Louisiana, United States
Investigational Site Number 840004
🇺🇸Hot Springs, Arkansas, United States
Investigational Site Number 840015
🇺🇸East Orange, New Jersey, United States
Investigational Site Number 840006
🇺🇸Pawtucket, Rhode Island, United States
Investigational Site Number 840008
🇺🇸Anaheim, California, United States
Investigational Site Number 840005
🇺🇸Rockville, Maryland, United States
Investigational Site Number 036012
🇦🇺Camperdown, Australia
Investigational Site Number 840024
🇺🇸Raleigh, North Carolina, United States
Investigational Site Number 840023
🇺🇸Jacksonville, Florida, United States
Investigational Site Number 840011
🇺🇸Jackson, Mississippi, United States
Investigational Site Number 032003
🇦🇷Salta, Argentina
Investigational Site Number 036013
🇦🇺Bankstown, Australia
Investigational Site Number 840003
🇺🇸Port St. Lucie, Florida, United States
Investigational Site Number 840017
🇺🇸St Louis Park, Minnesota, United States
Investigational Site Number 036008
🇦🇺Coffs Harbour, Australia
Investigational Site Number 036010
🇦🇺Box Hill, Australia
Investigational Site Number 036014
🇦🇺Adelaide, Australia
Investigational Site Number 152005
🇨🇱Santiago, Chile
Investigational Site Number 056001
🇧🇪Bruxelles, Belgium
Investigational Site Number 056011
🇧🇪Ottignies, Belgium
Investigational Site Number 036009
🇦🇺Fitzroy, Australia
Investigational Site Number 250008
🇫🇷Hyeres, France
Investigational Site Number 124003
🇨🇦Ottawa, Canada
Investigational Site Number 056008
🇧🇪Brussel, Belgium
Investigational Site Number 036016
🇦🇺Subiaco, Australia
Investigational Site Number 152001
🇨🇱Viña Del Mar, Chile
Investigational Site Number 152004
🇨🇱Santiago, Chile
Investigational Site Number 056003
🇧🇪Gent, Belgium
Investigational Site Number 076014
🇧🇷Porto Alegre, Brazil
Investigational Site Number 056007
🇧🇪Antwerpen, Belgium
Investigational Site Number 056005
🇧🇪Hasselt, Belgium
Investigational Site Number 056006
🇧🇪Turnhout, Belgium
Investigational Site Number 076016
🇧🇷Fortaleza, Brazil
Investigational Site Number 076015
🇧🇷Mogi Das Cruzes, Brazil
Investigational Site Number 056004
🇧🇪Roeselare, Belgium
Investigational Site Number 076012
🇧🇷Ijui, Brazil
Investigational Site Number 276004
🇩🇪Düsseldorf, Germany
Investigational Site Number 250005
🇫🇷Avignon Cedex 9, France
Investigational Site Number 076009
🇧🇷Sao Paulo, Brazil
Investigational Site Number 124005
🇨🇦Owen Sound, Canada
Investigational Site Number 152002
🇨🇱Santiago, Chile
Investigational Site Number 250001
🇫🇷La Roche Sur Yon, France
Investigational Site Number 276006
🇩🇪München, Germany
Investigational Site Number 276011
🇩🇪Hamburg, Germany
Investigational Site Number 276007
🇩🇪Dresden, Germany
Investigational Site Number 276003
🇩🇪Aachen, Germany
Investigational Site Number 348001
🇭🇺Budapest, Hungary
Investigational Site Number 276001
🇩🇪Erlangen, Germany
Investigational Site Number 410003
🇰🇷Seongnam, Korea, Republic of
Investigational Site Number 528002
🇳🇱Nijmegen, Netherlands
Investigational Site Number 604007
🇵🇪Lima, Peru
Investigational Site Number 616006
🇵🇱Lubin, Poland
Investigational Site Number 604005
🇵🇪Lima, Peru
Investigational Site Number 616001
🇵🇱Rybnik, Poland
Investigational Site Number 642001
🇷🇴Cluj Napoca, Romania
Investigational Site Number 642006
🇷🇴Baia Mare, Romania
Investigational Site Number 643006
🇷🇺Moscow, Russian Federation
Investigational Site Number 643001
🇷🇺St.Petersburg, Russian Federation
Investigational Site Number 643003
🇷🇺Tula, Russian Federation
Investigational Site Number 788003
🇹🇳Sousse, Tunisia
Investigational Site Number 710004
🇿🇦Johannesburg, South Africa
Investigational Site Number 710003
🇿🇦Cape Town, South Africa
Investigational Site Number 710001
🇿🇦Pretoria, South Africa
Investigational Site Number 710002
🇿🇦Durban, South Africa
Investigational Site Number 158001
🇨🇳Taipei, Taiwan
Investigational Site Number 724002
🇪🇸Madrid, Spain
Investigational Site Number 788004
🇹🇳Sfax, Tunisia
Investigational Site Number 724006
🇪🇸Málaga, Spain
Investigational Site Number 724007
🇪🇸Sevilla, Spain
Investigational Site Number 724004
🇪🇸Sabadell, Spain
Investigational Site Number 792002
🇹🇷Istanbul, Turkey
Investigational Site Number 826001
🇬🇧Sutton, United Kingdom
Investigational Site Number 826003
🇬🇧Newcastle Upon Tyne, United Kingdom
Investigational Site Number 276010
🇩🇪Homburg, Germany
Investigational Site Number 276005
🇩🇪Hamburg, Germany
Investigational Site Number 250002
🇫🇷Nantes Cedex 2, France
Investigational Site Number 250004
🇫🇷Nimes, France
Investigational Site Number 250007
🇫🇷Reims, France
Investigational Site Number 250006
🇫🇷Saint Brieuc Cedex, France
Investigational Site Number 250003
🇫🇷Toulouse Cedex 09, France
Investigational Site Number 410002
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410004
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 724003
🇪🇸Badalona, Spain
Investigational Site Number 724005
🇪🇸Palma De Mallorca, Spain
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 036006
🇦🇺South Brisbane, Australia
Investigational Site Number 036001
🇦🇺Concord, Australia
Investigational Site Number 036007
🇦🇺Garran, Australia
Investigational Site Number 032002
🇦🇷Buenos Aires, Argentina
Investigational Site Number 840010
🇺🇸La Jolla, California, United States
Investigational Site Number 840001
🇺🇸San Bernardino, California, United States
Investigational Site Number 036004
🇦🇺Wodonga, Australia
Investigational Site Number 840013
🇺🇸Lakeland, Florida, United States
Investigational Site Number 032001
🇦🇷Rosario, Argentina
Investigational Site Number 032004
🇦🇷Santa Fe, Argentina
Investigational Site Number 840025
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 036015
🇦🇺Elizabeth Vale, Australia
Investigational Site Number 036005
🇦🇺Heidelberg West, Australia
Investigational Site Number 036002
🇦🇺Malvern, Australia
Investigational Site Number 036003
🇦🇺Wahroonga, Australia
Investigational Site Number 056012
🇧🇪Godinne, Belgium
Investigational Site Number 056010
🇧🇪Libramont, Belgium
Investigational Site Number 056013
🇧🇪Liège, Belgium
Investigational Site Number 076010
🇧🇷Rio De Janeiro, Brazil
Investigational Site Number 076002
🇧🇷Sao Paulo, Brazil
Investigational Site Number 076013
🇧🇷Sao Paulo, Brazil
Investigational Site Number 124002
🇨🇦Greenfield Park, Canada
Investigational Site Number 124001
🇨🇦Oshawa, Canada
Investigational Site Number 250010
🇫🇷Paris, France
Investigational Site Number 250009
🇫🇷Reims Cedex, France
Investigational Site Number 250011
🇫🇷Toulouse Cedex 03, France
Investigational Site Number 276002
🇩🇪Wuppertal, Germany
Investigational Site Number 276012
🇩🇪Nürtingen, Germany
Investigational Site Number 276008
🇩🇪Tübingen, Germany
Investigational Site Number 348005
🇭🇺Budapest, Hungary
Investigational Site Number 348004
🇭🇺Budapest, Hungary
Investigational Site Number 348003
🇭🇺Pécs, Hungary
Investigational Site Number 348006
🇭🇺Miskolc, Hungary
Investigational Site Number 410005
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 410001
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 528005
🇳🇱Arnhem, Netherlands
Investigational Site Number 528003
🇳🇱Blaricum, Netherlands
Investigational Site Number 528004
🇳🇱Hoofddorp, Netherlands
Investigational Site Number 604003
🇵🇪Arequipa, Peru
Investigational Site Number 616004
🇵🇱Torun, Poland
Investigational Site Number 642009
🇷🇴Bucuresti, Romania
Investigational Site Number 642008
🇷🇴Bucuresti, Romania
Investigational Site Number 643007
🇷🇺Moscow, Russian Federation
Investigational Site Number 643009
🇷🇺Ekaterinburg, Russian Federation
Investigational Site Number 643005
🇷🇺Moscow, Russian Federation
Investigational Site Number 643004
🇷🇺Moscow, Russian Federation
Investigational Site Number 643008
🇷🇺Obninsk, Russian Federation
Investigational Site Number 643010
🇷🇺St.Petersburg, Russian Federation
Investigational Site Number 710005
🇿🇦Johannesburg, South Africa
Investigational Site Number 724008
🇪🇸Madrid, Spain
Investigational Site Number 792003
🇹🇷Antalya, Turkey
Investigational Site Number 792001
🇹🇷Bornova, Turkey
Investigational Site Number 826002
🇬🇧Birmingham, United Kingdom
Investigational Site Number 826004
🇬🇧Colchester, United Kingdom
Investigational Site Number 826005
🇬🇧Glasgow, United Kingdom
Investigational Site Number 826007
🇬🇧Manchester, United Kingdom
Investigational Site Number 826006
🇬🇧Guildford, United Kingdom
Investigational Site Number 616002
🇵🇱Olsztyn, Poland
Investigational Site Number 616005
🇵🇱Siedlce, Poland