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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00603746




Registration number
NCT00603746
Ethics application status
Date submitted
27/12/2007
Date registered
29/01/2008

Titles & IDs
Public title
A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Moderate-Dose ICS Therapy.
Scientific title
A Randomized Double-Blind, Double Dummy, Placebo-Controlled, Parallel-Group, Multicenter Dose Ranging Study to Evaluate the Efficacy and Safety of GW685698X Inhalation Powder Once Daily and Fluticasone Propionate Inhalation Powder 500mcg Twice Daily Compared With Placebo for 8 Weeks in Adolescent an
Secondary ID [1] 0 0
FFA109684
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GW685698X

Experimental: GW685698X - GW685698X


Treatment: Drugs: GW685698X
GW685698X

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8
Timepoint [1] 0 0
Baseline and Week 8
Secondary outcome [1] 0 0
Mean Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Averaged Over the 8-week Treatment Period
Timepoint [1] 0 0
From Baseline up to Week 8
Secondary outcome [2] 0 0
Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period
Timepoint [2] 0 0
From Baseline up to Week 8
Secondary outcome [3] 0 0
Mean Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 8-week Treatment Period
Timepoint [3] 0 0
From Baseline up to Week 8
Secondary outcome [4] 0 0
Mean Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 8-week Treatment Period
Timepoint [4] 0 0
From Baseline up to Week 8
Secondary outcome [5] 0 0
Number Participants Who Withdrew Due to Lack of Efficacy During the 8-week Treatment Period
Timepoint [5] 0 0
From the first dose of the study medication up to Week 8/Early Withdrawal
Secondary outcome [6] 0 0
Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event Throughout the 8-week Treatment Period
Timepoint [6] 0 0
From the first dose of the study medication up to Week 8/Early Withdrawal
Secondary outcome [7] 0 0
Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis
Timepoint [7] 0 0
From Baseline up to Week 8/Early Withdrawal
Secondary outcome [8] 0 0
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8
Timepoint [8] 0 0
Baseline and Week 8
Secondary outcome [9] 0 0
Hematocrit at Baseline and Week 8
Timepoint [9] 0 0
Baseline and Week 8
Secondary outcome [10] 0 0
Hemoglobin at Baseline and Week 8
Timepoint [10] 0 0
Baseline and Week 8
Secondary outcome [11] 0 0
Platelet Count and White Blood Cell Count at Baseline and Week 8
Timepoint [11] 0 0
Baseline and Week 8
Secondary outcome [12] 0 0
Red Blood Cell Count at Baseline and Week 8
Timepoint [12] 0 0
Baseline and Week 8
Secondary outcome [13] 0 0
Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LDH) at Baseline and Week 8
Timepoint [13] 0 0
Baseline and Week 8
Secondary outcome [14] 0 0
Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8
Timepoint [14] 0 0
Baseline and Week 8
Secondary outcome [15] 0 0
Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/Bicarbonate, Chloride, Cholesterol, Glucose, Phosphorus Inorganic, Potassium, Sodium, and Urea at Baseline and Week 8
Timepoint [15] 0 0
Baseline and Week 8
Secondary outcome [16] 0 0
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8
Timepoint [16] 0 0
Baseline and Week 8
Secondary outcome [17] 0 0
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Withdrawal
Timepoint [17] 0 0
Baseline and Week 8/Early Withdrawal
Secondary outcome [18] 0 0
Urine Specific Gravity at Baseline and Week 8/Early Withdrawal
Timepoint [18] 0 0
Baseline and Week 8/Early Withdrawal
Secondary outcome [19] 0 0
Urine pH at Baseline and Week 8/Early Withdrawal
Timepoint [19] 0 0
Baseline and Week 8/Early Withdrawal
Secondary outcome [20] 0 0
24-hour Urinary Cortisol Excretion at Baseline and Week 8
Timepoint [20] 0 0
Baseline and Week 8
Secondary outcome [21] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8
Timepoint [21] 0 0
Baseline and Week 8
Secondary outcome [22] 0 0
Change From Baseline in Heart Rate at Week 8
Timepoint [22] 0 0
Baseline and Week 8

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

Subjects eligible for enrolment in the study must meet all of the following criteria:

* Type of Subject: Outpatient
* Age: 12 years of age or older at Visit 1. For sites in the following countries, subjects recruited will be =18 years of age: Bulgaria, Czech Republic, Germany, Greece, Lithuania, New Zealand, Russian Federation, Turkey and any other countries where local regulations or the regulatory status of study medication permit enrolment of adults only.
* 3. Gender: Male or Eligible Female
* To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:
* Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject
* Implants of levonorgestrel
* Injectable progestogen
* Oral contraceptive (either combined estrogen/progestin or progestin only)
* Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.
* Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial and for a period after the trial to account for elimination of the drug (minimum of six days).
* Double barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm).
* NB: For German sites, female subjects must use a method of birth control other than the double barrier method.
* The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds)
* Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation. A serum pregnancy test is required of all females. This test will be performed at the initial screening visit (Visit 1) and Visit 8. In addition, a urine pregnancy test will be performed on the evening of the double-blind treatment visit, prior to randomization (Visit 3) and at Visits 4 through 7.
* Asthma Diagnosis: Asthma as defined by the National Institutes of Health [National Institutes of Health, 2007].
* Severity of Disease: A best FEV1 of 40%-85% of the predicted normal value during the morning Visit 1 screening period or a best FEV1 of 40%-90% of the predicted normal value during the evening Visit 1 screening period.
* Reversibility of Disease: Demonstrated a = 12% and =200mL reversibility of FEV1 within approximately 30-minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers are permitted for reversibility testing only) or one nebulized albuterol/salbutamol solution during the screening period.

Re-screening of subjects during the Visit 1 screening period: If a subject does not meet the inclusion criteria based upon FEV1 percent predicted and/or reversibility, the subject may return to the site once within 4 days and repeat the lung function tests.

* Current Anti-Asthma Therapy: Subjects must have been using a inhaled corticosteroid for at least 8 weeks prior to Visit 1 and maintained on a stable dose of inhaled corticosteroids for four weeks prior to Visit 1 at one of the following doses: [fluticasone propionate MDI CFC/HFA >176 = 440mcg exactuator or > 200 =500mcg ex valve]; [fluticasone propionate DPI > 200=500mcg]; [beclomethasone dipropionate DPI > 420 = 840mcg exactuator or > 500 = 1000mcg ex-valve]; [beclomethasone dipropionate HFA Qvar > 160 = 480mcg exactuator or > 200 = 500mcg ex-valve]; [budesonide DPI MDI >400 =1200mcg]; [flunisolide > 1000 = 2000mcg]; [triamcinolone acetonide >1000 =1600mcg]; [mometasone furoate DPI >200 = 440mcg]; [ciclesonide MDI HFA >160 mcg = 320mcg ex-actuator dose / >200mcg = 400mcg ex-valve dose}
* Short- Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as needed for the duration of the study. The use of spacer devices with metered dose inhaler (MDI) or nebulized albuterol/salbutamol will not be allowed during the study with the exception of their use during reversibility testing at Visit 1. Subjects must be able to withhold all inhaled short-acting beta sympathomimetic bronchodilators for at least 6 hours prior to all study visits.
* Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.
* Compliance: Subjects must be able to comply with completion of the Daily Diary (includes paper medical conditions diary).
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Inclusion Criteria for Randomization

At the end of the run-in period, a subject will be eligible to enter the treatment period of the study if he/she meets the following criteria at Visit 3:

1. Evening pre-dose percent predicted FEV1 of between 40% and 90% of their predicted normal.
2. Any combination of the daily asthma symptom scores (day-time plus night-time) of =1 or albuterol/salbutamol use on at least 4 of the last 7 consecutive days of the run-in period (immediately preceding Visit 3).

EXCLUSION CRITERIA:

* History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.
* Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subject's asthma status or the subject's ability to participate in the study.
* Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1. A subject must not have had any hospitalization for asthma within 6 months prior to Visit 1.
* Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease including, but not limited to: cardiovascular disease, hepatic disease, renal disease, hematological disease, neurological disease, or pulmonary disease (including, but not confined to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. The list of additional excluded conditions/diseases includes, but is not limited to the following: congestive heart failure, clinically significant coronary artery disease, stroke within 3 months of Visit 1, poorly controlled peptic ulcer, immunologic compromise, tuberculosis (current or untreated), Addison's disease, uncontrolled thyroid disorder, known aortic aneurysm, clinically significant cardiac arrhythmia, uncontrolled hypertension, hematological, hepatic, or renal disease, current malignancy, cushings disease, uncontrolled diabetes mellitus, recent history of drug or alcohol abuse.
* Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of oral candidiasis at Visit 1.
* Investigational Medications: A subject must not have participated in a study or used any investigational drug within 30 days prior to Visit 1.
* Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the novel dry powder inhaler or DISKUS/ACCUHALER (i.e., lactose or magnesium stearate).
* Milk Protein Allergy: History of severe milk protein allergy.
* Immunosuppressive Medications: A subject must not be using, or require use, of immunosuppressive medications during the study. NOTE: Immunotherapy for the treatment of allergies is allowed during the study provided that the treatment was initiated prior to Visit 1 and the subject is maintained on a stable regimen throughout the study period.
* Attendance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol or scheduled visits to the study center and non-compliant with study medication or procedures (e.g. completion of daily diary). Neurological or psychiatric disease or history of drug or alcohol abuse which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirements excludes study participation.
* Tobacco Use : Current smoker or a smoking history of 10 pack years or more (e.g. 20 cigarettes/day for 10 years). A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco).
* Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.
* Corticosteroid Use: Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1.
* Potent Cytochrome P450 3A4 (CYP3A4) inhibitors: Patients who are receiving potent CYP3A4 inhibitors within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for Randomization At the end of the run-in period, a subject will not be eligible to enter the treatment period of the study if they meet any of the following criteria.

1. Clinical Laboratory Abnormalities: Clinically significant abnormal laboratory tests during Visit 1 which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality. When in doubt, GlaxoSmithKline, or designee, should be notified so that a joint decision can be made.
2. Changes in asthma medication (excluding albuterol/salbutamol inhalation aerosol provided at Visit 1).
3. Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subject's asthma status or the subject's ability to participate in the study.
4. Asthma exacerbation, defined as any worsening of asthma requiring any treatment other than rescue albuterol/salbutamol or regular inhaled corticosteroid use. This includes requiring the use of systemic corticosteroids and / or emergency room visit or hospitalization or a change in subject's regular inhaled corticosteroid dose.
5. A subject will not be eligible for randomization if he/she has an abnormal visual oropharyngeal exam at the randomization Visit 3 (visual clinical evidence of oral candidiasis).
6. Non-compliance with completion of the Daily Diary, defined as: -Completion of AM and PM symptom scores on less than 4 days out of the last 7 days immediately preceding Visit 3.

* Completion of AM and PM rescue use on less than 4 days out of the last 7 days immediately preceding Visit 3.
* Completion of AM and PM PEF measurements on less than 4 days out of the last 7 days immediately preceding Visit 3.
* Recording run-in asthma medication use on less than 4 days out of the last 7 days immediately preceding Visit 3.

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?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [2] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kansas
Country [12] 0 0
United States of America
State/province [12] 0 0
Kentucky
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maine
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Minnesota
Country [18] 0 0
United States of America
State/province [18] 0 0
Mississippi
Country [19] 0 0
United States of America
State/province [19] 0 0
Missouri
Country [20] 0 0
United States of America
State/province [20] 0 0
Montana
Country [21] 0 0
United States of America
State/province [21] 0 0
Nevada
Country [22] 0 0
United States of America
State/province [22] 0 0
New Jersey
Country [23] 0 0
United States of America
State/province [23] 0 0
New York
Country [24] 0 0
United States of America
State/province [24] 0 0
North Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
Ohio
Country [26] 0 0
United States of America
State/province [26] 0 0
Oklahoma
Country [27] 0 0
United States of America
State/province [27] 0 0
Oregon
Country [28] 0 0
United States of America
State/province [28] 0 0
Pennsylvania
Country [29] 0 0
United States of America
State/province [29] 0 0
South Carolina
Country [30] 0 0
United States of America
State/province [30] 0 0
Tennessee
Country [31] 0 0
United States of America
State/province [31] 0 0
Texas
Country [32] 0 0
United States of America
State/province [32] 0 0
Vermont
Country [33] 0 0
United States of America
State/province [33] 0 0
Virginia
Country [34] 0 0
United States of America
State/province [34] 0 0
Washington
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Pleven
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Ruse
Country [37] 0 0
Bulgaria
State/province [37] 0 0
Sofia
Country [38] 0 0
Canada
State/province [38] 0 0
Newfoundland and Labrador
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
Chile
State/province [41] 0 0
Región Metro De Santiago
Country [42] 0 0
Chile
State/province [42] 0 0
Valparaíso
Country [43] 0 0
Chile
State/province [43] 0 0
Santiago
Country [44] 0 0
Czechia
State/province [44] 0 0
Beroun
Country [45] 0 0
Czechia
State/province [45] 0 0
Brno
Country [46] 0 0
Czechia
State/province [46] 0 0
Kutna Hora
Country [47] 0 0
Czechia
State/province [47] 0 0
Tabor
Country [48] 0 0
Estonia
State/province [48] 0 0
Tallinn
Country [49] 0 0
Estonia
State/province [49] 0 0
Tartu
Country [50] 0 0
France
State/province [50] 0 0
Grenoble
Country [51] 0 0
France
State/province [51] 0 0
Marseille
Country [52] 0 0
France
State/province [52] 0 0
Montpellier
Country [53] 0 0
France
State/province [53] 0 0
Nantes
Country [54] 0 0
Germany
State/province [54] 0 0
Hessen
Country [55] 0 0
Germany
State/province [55] 0 0
Niedersachsen
Country [56] 0 0
Germany
State/province [56] 0 0
Berlin
Country [57] 0 0
Mexico
State/province [57] 0 0
Jalisco
Country [58] 0 0
Mexico
State/province [58] 0 0
Distrito Federal
Country [59] 0 0
Mexico
State/province [59] 0 0
Mexico
Country [60] 0 0
Netherlands
State/province [60] 0 0
Amsterdam
Country [61] 0 0
Netherlands
State/province [61] 0 0
Eindhoven
Country [62] 0 0
Netherlands
State/province [62] 0 0
Hengelo
Country [63] 0 0
Netherlands
State/province [63] 0 0
Schiedam
Country [64] 0 0
Netherlands
State/province [64] 0 0
Utrecht
Country [65] 0 0
Peru
State/province [65] 0 0
Lima
Country [66] 0 0
Poland
State/province [66] 0 0
Bialystok
Country [67] 0 0
Poland
State/province [67] 0 0
Warszawa
Country [68] 0 0
Poland
State/province [68] 0 0
Wroclaw
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Irkutsk
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Kazan
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Moscow
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Tomsk
Country [73] 0 0
South Africa
State/province [73] 0 0
Amanzimtoti
Country [74] 0 0
South Africa
State/province [74] 0 0
Bellville
Country [75] 0 0
South Africa
State/province [75] 0 0
Durban
Country [76] 0 0
South Africa
State/province [76] 0 0
Mowbray
Country [77] 0 0
Thailand
State/province [77] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.