FLASH: Study to Assess the Efficacy and Safety of AZD5718 in Moderate-to-Severe Uncontrolled Asthma

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05251259

Collaborator

(none)

1,900

Enrollment

177

Locations

Arms

24.4

Anticipated Duration (Months)

10.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomised, placebo-controlled, double-blind study with an active comparator (montelukast) arm to assess the efficacy and safety of AZD5718 administered at multiple dose levels over a 12-week treatment period to adult participants with moderate-to-severe uncontrolled asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: AZD5718 Drug: Placebo Drug: Montelukast	Phase 2

Detailed Description

The study will enroll participants with moderate-to-severe uncontrolled asthma who are on low-dose inhaled corticosteroid (ICS) - a long-acting beta-agonist (LABA) or medium-to-high-dose ICS with or without LABA background treatment.

The study will be performed as a 2-part study Part 1 and Part 2 with a Lead-in pharmacokinetics (PK) cohort.

In the Lead-in PK cohort, participants will be randomised to AZD5718 or placebo.

In Part 1 of the study, participants will be randomised 1:1 to AZD5718 or placebo.

In Part 2 of the study, participants will be randomised to 1 of 5 treatment groups (AZD5718:

Dose A, B, C, montelukast or placebo).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1900 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Randomised, Double-Blind, Placebo and Active Comparator-Controlled Study to Assess Efficacy and Safety of Multiple Dose Levels of AZD5718 Given Orally Once Daily for Twelve Weeks in Adults With Moderate-to-Severe Uncontrolled Asthma

Actual Study Start Date :

Jan 27, 2022

Anticipated Primary Completion Date :

Feb 8, 2024

Anticipated Study Completion Date :

Feb 8, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lead-in PK Cohort (AZD5718 Dose A) Randomized participants will receive AZD5718 dose A	Drug: AZD5718 Randomized participants will receive AZD5718
Experimental: Part 1: AZD5718 Dose A Randomised participants will receive AZD5718 Dose A	Drug: AZD5718 Randomized participants will receive AZD5718
Experimental: Part 2: AZD5718 Dose A Randomised participants will receive AZD5718 Dose A	Drug: AZD5718 Randomized participants will receive AZD5718
Experimental: Part 2: AZD5718 Dose B Randomised participants will receive AZD5718 Dose B	Drug: AZD5718 Randomized participants will receive AZD5718
Experimental: Part 2: AZD5718 Dose C Randomised participants will receive AZD5718 Dose C	Drug: AZD5718 Randomized participants will receive AZD5718
Active Comparator: Part 2: Montelukast Dose X Participants will receive montelukast dose X	Drug: Montelukast Randomized participants will receive montelukast
Placebo Comparator: Lead-in PK, Part 1 and Part 2 Placebo Randomized participants will receive placebo	Drug: Placebo Randomized participants will receive placebo

Outcome Measures

Primary Outcome Measures

Time to first CompEx Asthma event (Composite endpoint for Exacerbations) [Baseline up to Week 12]
The clinical efficacy of AZD5718 Dose A will be assessed by calculating a Hazard Ratio between the following treatment arms: a) AZD5718 Dose A vs. placebo; b) AZD5718 Dose A vs. Montelukast. CompEx Asthma, a novel composite endpoint for exacerbations, captures asthma-worsening episodes based on a combination of diary events (worsening in daily PEF, asthma symptoms and reliever medication use) plus severe asthma exacerbation events.

Secondary Outcome Measures

Time to first CompEx Asthma event (Composite endpoint for Exacerbations) [Baseline up to Week 12]
The clinical efficacy of AZD5718 Dose A will be identified using the Hazard Ratio of AZD5718 Dose A vs. placebo.
Time to first CompEx Asthma event (Composite endpoint for Exacerbations) [Baseline up to Week 12]
The clinical efficacy of AZD5718 at different dose levels compared to placebo will be assessed by calculating a Hazard Ratio between the following treatment arms: a) AZD5718 Dose A compared to placebo; b) AZD5718 Dose B compared to placebo; c) AZD5718 Dose C compared to placebo
Time to first CompEx Asthma event (Composite endpoint for Exacerbations) [Baseline up to Week 12]
The clinical efficacy of AZD5718 Dose A will be assessed by calculating the Hazard Ratio of AZD5718 Dose A vs. placebo.
Change from baseline in Pre-bronchodilator forced expiratory volume in 1 second [Baseline, Week 4 and Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to montelukast in adult participants with moderate-to-severe uncontrolled asthma
Change from baseline in St. George's Respiratory Questionnaire [Baseline, Week 4 and Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to Montelukast in adult participants with moderate-to-severe uncontrolled asthma. The St. George's Respiratory Questionnaire (SGRQ) is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The questionnaire is divided into two parts: part one consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and three domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status.
Change from baseline in Asthma Control Questionnaire 6 [Baseline Week 4, Week 8, Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to Montelukast in adult participants with moderate-to-severe uncontrolled asthma. The Asthma Control Questionnaire 6 (ACQ-6) has 6 questions (the top scoring 5 symptoms and daily rescue bronchodilator use). The symptom and bronchodilator use questions on a 7-point scale (0 = no impairment, 6 = maximum impairment). Score 0 means totally controlled and 6 reflects severely uncontrolled.
Change from baseline in average morning and evening Peak Flow Measurement [Baseline Week 4, Week 8, Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to Montelukast in adult participants with moderate-to-severe uncontrolled asthma.
Change from baseline in Daily asthma symptom score (total, daytime, and night-time) [Baseline Week 4, Week 8, Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to Montelukast in adult participants with moderate-to-severe uncontrolled asthma. Asthma symptom scores during night-time and day-time will be assessed by the participant each morning and evening according to the following scoring system: (0) You have no asthma symptoms; (1): You are aware of your asthma symptoms, but you can easily tolerate the symptoms; (2): Your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep); (3): You are unable to do your normal activities (or to sleep) because of your asthma. Here, low score reflects no asthma symptoms and high score suggests severe or frequent symptoms.
Time to first severe asthma exacerbation [Baseline up to Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to montelukast in adult participants with moderate-to-severe uncontrolled asthma.
Event status (CompEx Asthma event yes/no) [Baseline up to Week 12]
To evaluate the clinical efficacy of AZD5718 as compared to placebo and as compared to Montelukast in adult participants with moderate-to-severe uncontrolled asthma.
Lead-in PK: Area under the curve (AUC) [Day 1 and Day 15]
PK parameter of AZD5718 will be assessed. Participants will be randomised to AZD5718 Dose A in the Lead-in PK Cohort.
Lead-in PK: Maximum (or peak) serum concentration (Cmax) [Day 1 and Day 15]
PK parameter of AZD5718 will be assessed. Participants will be randomised to AZD5718 Dose A in the Lead-in PK Cohort.
Lead-in PK cohort: Pre-dose trough concentration (Ctrough) [Day 15]
PK parameter of AZD5718 will be assessed. Participants will be randomised to AZD5718 Dose A in the Lead-in PK Cohort.
AZD5718 plasma concentrations in a subset of participants, post-dose samples [Week 4]
To summarise AZD5718 post-dose plasma concentrations.
AZD5718 plasma concentrations in all participants, pre-dose samples [Baseline, Week 4 and Week 12]
To summarise AZD5718 pre-dose plasma concentrations.
Number of participants with adverse events (AEs) [Baseline up to Week 12]
To assess the safety and tolerability of AZD5718 in adult participants with moderate-to-severe uncontrolled asthma.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Lead-in PK Cohort:

18 to 55 years of age inclusive at the time of signing the informed consent at Visit

Bodyweight 50 to 100 kg (inclusive) and BMI 18 to 30 kg/m^2 (inclusive) at Visit 1.
Documented asthma diagnosis ≥ 12 months prior to Visit 1.
Able to perform acceptable lung function testing for FEV1 according to American Thoracic Society / European Respiratory Society (ATS/ERS) 2019 acceptability criteria.
Morning pre- bronchodilator (BD) forced expiratory volume (FEV)1 ≥ 70% predicted at Visit 1 and Visit 2.
Treated with low dose inhaled corticosteroid plus long-acting β2-agonist (ICS-LABA) or medium-high dose ICS alone or in combination with LABA at a stable dose for at least 3 months prior to Visit 1. Also, treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 3 months prior to Visit 1 is allowed.
Participant's influenza/pneumonia vaccination is up to date as per local guidelines prior to Visit 2.

Part 1 and Part 2: Specific Inclusion Criteria for Pre-Screening:

Participant must be 18 to 80 years of age inclusive at the time of signing the informed consent
Treated with low dose ICS-LABA or medium-high dose ICS alone or in combination with LABA at a stable dose for at least 3 months prior to Visit 1.
Documented history of ≥ 1 severe asthma exacerbation within 12 months prior to Visit

Morning pre-BD FEV1 between ≥ 40% and ≤ 80% predicted at Visit 0.
Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.

Specific Biomarker Inclusion Criteria for Part 1:

Test for prospective biomarkers will be performed at visit 0 or 1.

General Inclusion Criteria for Part 1 and Part 2:

Body weight ≥ 40 kg and body mass index (BMI) < 35 kg/m^2.
Documented physician-diagnosed asthma ≥ 12 months prior to Visit 1.
Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria.
Morning pre-BD FEV1 between ≥ 40% and ≤ 80% predicted at Visit 1 and at Visit 3.
An Asthma Control Questionnaire (ACQ)-6 score ≥ 1.5 at Visit 1 and at Visit 3.
Participant's influenza/pneumonia vaccination is up to date as per local guidelines prior to Visit 2.

Additional Specific Criteria for Visit 3 (randomisation):

Pre-bronchodilator FEV1 between ≥ 40% and ≤ 80% predicted.
ACQ-6 score of ≥ 1.5.
At least 80% compliance with usual asthma background medication during run-in period (from Visit 2 to Visit 3) based on the daily asthma electronic patient-reported outcome (ePROs).

Exclusion Criteria

A severe asthma exacerbation within 8 weeks of randomisation.
A positive nucleic acid test (eg Real Time-Polymerase Chain Reaction) at Visit 1 or at Visit 3 for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for Coronavirus disease 2019 (COVID-19).
Participants with a significant COVID-19 illness within 6 months of enrolment.
Clinically important pulmonary disease other than asthma.
Galactose intolerance, Lapp lactase deficiency, or glucose-galactose metabolism.
Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable.
Any clinically significant cardiac disease.
History of severe renal disease or history of creatinine clearance < 30 mL/min × m2 calculated using Cockcroft-Gault equation.
Severe hepatic impairment (Child-Pugh class C).
Previous hepatotoxicity related to zileuton or leukotriene receptor antagonist (LTRAs) (eg montelukast).
Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
Evidence of active or untreated latent tuberculosis (TB).
History of or current alcohol or drug abuse (including marijuana).
Current diagnosis of cancer, not including in-situ or non-melanoma skin cancer or other previous malignancies where curative therapy was completed at least 5 years prior to Visit 1.
Clinically important ongoing or previous psychiatric disease, especially suicidal behaviour, that in the opinion of the investigator might compromise the safety of the participant in the study.
Treatment with any serum creatinine-altering drugs within 1 month prior to Visit 1 including but not limited to amphotericin, cimetidine, clofibrate, dronedarone, ketoconazole, probenecid, ranolazine, trimethoprim, aminoglycosides, or cephalosporins.
Treatment with systemic corticosteroid use within 8 weeks (oral) or 12 weeks (intramuscular) before Visit 1.
Treatment with marketed biologics including benralizumab, mepolizumab, reslizumab, omalizumab, and dupilumab within 6 months of Visit 1 or 5 half-lives whichever is longer.
Treatment with LTRAs or 5-lipoxygenase inhibitors (eg zileuton and montelukast; at least 8 weeks prior to Visit 1).
Inhaled corticosteroid + fast-acting β2 agonist as a reliever (eg Symbicort or Fostair Maintenance and Reliever Treatment) is not allowed 15 days prior to Visit 1, during screening/run-in and the treatment period and preferably 1 week after the last dose of study intervention.
Live or attenuated vaccines within 4 weeks of Visit 1.
Immunoglobulin or blood products within 4 weeks of Visit 1.
Treatment with Gemfibrozil within 4 weeks of Visit 1.
Any immunotherapy within 6 months of Visit 1, except for stable maintenance dose allergen-specific immunotherapy started at least 4 weeks prior to Visit 1 and expected to continue through to the end of the follow-up period.
Investigational products within 4 months or 5 half-lives of Visit 1.
Potent inducers/inhibitors of cytochrome P450 3A4 within 4 weeks of Visit 1.
Treatment with simvastatin, lovastatin, and atorvastatin at doses > 40 mg per day within 1 month prior to Visit 1. Treatment with sensitive cytochrome 3A substrates with narrow therapeutic window should be avoided from randomization to study drug.
For female participants on ethinyl estradiol containing combined oral contraceptives.
Concurrent enrolment in another clinical study.
Participant treated with any investigational drug within 30 days prior to Visit 1.
Known history of allergy or reaction to any component of the study intervention formulation.
For female participants only: Currently pregnant or breast-feeding.
Current smokers or participants with smoking history ≥ 10 pack-years.
Involvement in the planning and/or conduct of the study.
Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1.
Major surgery within 8 weeks prior to Visit 1, or planned inpatient surgery, major dental procedure or hospitalisation during the screening, treatment or follow-up periods.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Sheffield	Alabama	United States	35660
2	Research Site	Bakersfield	California	United States	93301
3	Research Site	Fountain Valley	California	United States	92708
4	Research Site	Huntington Beach	California	United States	92647
5	Research Site	San Diego	California	United States	92120
6	Research Site	San Jose	California	United States	95117
7	Research Site	Clearwater	Florida	United States	33765
8	Research Site	Coral Gables	Florida	United States	33145
9	Research Site	Cutler Bay	Florida	United States	33157
10	Research Site	Cutler Bay	Florida	United States	33189
11	Research Site	Hialeah	Florida	United States	33010
12	Research Site	Hialeah	Florida	United States	33012
13	Research Site	Hialeah	Florida	United States	33016
14	Research Site	Hollywood	Florida	United States	33024
15	Research Site	Miami Springs	Florida	United States	33166
16	Research Site	Miami	Florida	United States	33125
17	Research Site	Miami	Florida	United States	33144
18	Research Site	Miami	Florida	United States	33155
19	Research Site	Miami	Florida	United States	33173
20	Research Site	Miami	Florida	United States	33174
21	Research Site	Miami	Florida	United States	33174
22	Research Site	Miami	Florida	United States	33175
23	Research Site	Miami	Florida	United States	33197
24	Research Site	Palmetto Bay	Florida	United States	33157
25	Research Site	Tampa	Florida	United States	33615
26	Research Site	Boise	Idaho	United States	83706
27	Research Site	Lexington	Kentucky	United States	40509
28	Research Site	Lexington	Kentucky	United States	40509
29	Research Site	Owensboro	Kentucky	United States	42301
30	Research Site	Oxon Hill	Maryland	United States	20745
31	Research Site	Ann Arbor	Michigan	United States	48105
32	Research Site	Buckley	Michigan	United States	49620
33	Research Site	Saint Louis	Missouri	United States	63141
34	Research Site	Bellevue	Nebraska	United States	68123
35	Research Site	Toms River	New Jersey	United States	08755
36	Research Site	Bronx	New York	United States	10455
37	Research Site	Horseheads	New York	United States	14845
38	Research Site	Gastonia	North Carolina	United States	28054
39	Research Site	Blue Ash	Ohio	United States	45242
40	Research Site	Oakwood	Ohio	United States	45409
41	Research Site	Toledo	Ohio	United States	43617
42	Research Site	Edmond	Oklahoma	United States	73034
43	Research Site	Altoona	Pennsylvania	United States	16602
44	Research Site	Pittsburgh	Pennsylvania	United States	15241
45	Research Site	Columbia	South Carolina	United States	29204
46	Research Site	Spartanburg	South Carolina	United States	29303
47	Research Site	Dallas	Texas	United States	75225
48	Research Site	Houston	Texas	United States	77022
49	Research Site	McKinney	Texas	United States	75069
50	Research Site	Pearland	Texas	United States	77581
51	Research Site	Tomball	Texas	United States	77375
52	Research Site	Clayton		Australia	3168
53	Research Site	Mitcham		Australia	3132
54	Research Site	South Brisbane		Australia	4101
55	Research Site	Kozloduy		Bulgaria	3320
56	Research Site	Montana		Bulgaria	3400
57	Research Site	Ruse		Bulgaria	7000
58	Research Site	Sofia		Bulgaria	1113
59	Research Site	Sofia		Bulgaria	1202
60	Research Site	Sofia		Bulgaria	1407
61	Research Site	Stara Zagora		Bulgaria	6003
62	Research Site	Velingrad		Bulgaria	4691
63	Research Site	Vidin		Bulgaria	3700
64	Research Site	Klenovnik		Croatia	42244
65	Research Site	Petrinja		Croatia	44250
66	Research Site	Rijeka		Croatia	51000
67	Research Site	Split		Croatia	21000
68	Research Site	Zabok		Croatia	49210
69	Research Site	Zagreb		Croatia	10 000
70	Research Site	Zagreb		Croatia	10000
71	Research Site	Bordeaux		France	33076
72	Research Site	Montpellier Cedex 5		France	34295
73	Research Site	Saint-Herblain		France	44800
74	Research Site	Strasbourg		France	67091
75	Research Site	Toulouse		France	31300
76	Research Site	Berlin		Germany	12203
77	Research Site	Marburg		Germany	35037
78	Research Site	Wiesbaden		Germany	65187
79	Research Site	Balassagyarmat		Hungary	2660
80	Research Site	Budapest		Hungary	1121
81	Research Site	Gyula		Hungary	5700
82	Research Site	Hajdúnánás		Hungary	4080
83	Research Site	Nyíregyháza		Hungary	4400
84	Research Site	Pécs		Hungary	7635
85	Research Site	Püspökladány		Hungary	4150
86	Research Site	Szombathely		Hungary	9700
87	Research Site	Battipaglia (SA)		Italy	84091
88	Research Site	Ferrara		Italy	44121
89	Research Site	Firenze		Italy	50134
90	Research Site	Milano		Italy	20123
91	Research Site	Monza		Italy	20090
92	Research Site	Napoli		Italy	80131
93	Research Site	Reggio Emilia		Italy	42123
94	Research Site	Roma		Italy	00168
95	Research Site	Rozzano		Italy	20089
96	Research Site	Siena		Italy	53100
97	Research Site	Verona		Italy	37126
98	Research Site	Chuo-ku		Japan	103-0022
99	Research Site	Chuo-ku		Japan	104-0031
100	Research Site	Fukuoka		Japan	811-1394
101	Research Site	Gifu		Japan	500-8717
102	Research Site	Himeji		Japan	672-8064
103	Research Site	Kodaira-shi		Japan	187-0024
104	Research Site	Kyoto-shi		Japan	601-8213
105	Research Site	Nagaoka-shi		Japan	940-8621
106	Research Site	Niigata		Japan	940-0840
107	Research Site	Osaka-shi		Japan	531-0073
108	Research Site	Shibuya-Ku		Japan	150-0013
109	Research Site	Toshima-ku		Japan	170-0003
110	Research Site	Toshima-ku		Japan	171-0014
111	Research Site	Yokohama-shi		Japan	223-0059
112	Research Site	Incheon		Korea, Republic of	405-760
113	Research Site	Seongnam-si		Korea, Republic of	13496
114	Research Site	Seongnam		Korea, Republic of	13620
115	Research Site	Seoul		Korea, Republic of	02841
116	Research Site	Seoul		Korea, Republic of	06591
117	Research Site	Seoul		Korea, Republic of	138-736
118	Research Site	Seoul		Korea, Republic of	6351
119	Research Site	Suwon-si		Korea, Republic of	16499
120	Research Site	Breda		Netherlands	4818 CK
121	Research Site	Groningen		Netherlands	9713 GZ
122	Research Site	Zutphens		Netherlands	7207 AE
123	Research Site	Grudziadz		Poland	86-300
124	Research Site	Katowice		Poland	40-282
125	Research Site	Katowice		Poland	40-611
126	Research Site	Kielce		Poland	25-751
127	Research Site	Krakow		Poland	31-455
128	Research Site	Kraków		Poland	31-513
129	Research Site	Ksawerów		Poland	95-054
130	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
131	Research Site	Ostróda		Poland	14-100
132	Research Site	Tarnów		Poland	33-100
133	Research Site	Warszawa		Poland	02-119
134	Research Site	Warszawa		Poland	02-793
135	Research Site	Warszawa		Poland	03-291
136	Research Site	Wrocław		Poland	53-301
137	Research Site	Łódź		Poland	90-153
138	Research Site	Łódź		Poland	90-302
139	Research Site	Brasov		Romania	500091
140	Research Site	Brasov		Romania	500283
141	Research Site	Bucuresti		Romania	010626
142	Research Site	Bucuresti		Romania	014461
143	Research Site	Caracal		Romania	235200
144	Research Site	Cluj-Napoca		Romania	400371
145	Research Site	Constanta		Romania	900673
146	Research Site	Deva		Romania	330084
147	Research Site	Iasi		Romania	700115
148	Research Site	Resca, Com. Dobrosloveni		Romania	237143
149	Research Site	Timisoara		Romania	300310
150	Research Site	Belgrade		Serbia	11000
151	Research Site	Belgrade		Serbia	11070
152	Research Site	Belgrade		Serbia	11080
153	Research Site	Sremska Kamenica		Serbia	21204
154	Research Site	Humenne		Slovakia	066 01
155	Research Site	Kezmarok		Slovakia	060 01
156	Research Site	Kosice		Slovakia	040 01
157	Research Site	Levice		Slovakia	934 01
158	Research Site	Presov		Slovakia	08001
159	Research Site	Surany		Slovakia	942 01
160	Research Site	Topolcany		Slovakia	95501
161	Research Site	Golnik		Slovenia	SI-4204
162	Research Site	Jesenice		Slovenia	4270
163	Research Site	Kamnik		Slovenia	1241
164	Research Site	Ljubljana		Slovenia	1000
165	Research Site	A Coruña		Spain	15001
166	Research Site	Badalona		Spain	08916
167	Research Site	Barcelona		Spain	08006
168	Research Site	Benalmádena		Spain	29631
169	Research Site	Madrid		Spain	28007
170	Research Site	Madrid		Spain	28031
171	Research Site	Málaga		Spain	29010
172	Research Site	Mérida		Spain	06802
173	Research Site	Sagunto(Valencia)		Spain	46520
174	Research Site	Vinnytsia		Ukraine	21001
175	Research Site	Leicester		United Kingdom	LE3 9QP
176	Research Site	London		United Kingdom	W1G 8HU
177	Research Site	Paddington		United Kingdom	W2 1NY