- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01934205
To Evaluate Plasma and Pulmonary Pharmacokinetics of GSK2140944
12. května 2017 aktualizováno: GlaxoSmithKline
An Open-label Study To Evaluate Plasma and Pulmonary Pharmacokinetics Following Intravenous Administration of GSK2140944 in Healthy Adult Subjects (BTZ116666)
Antimicrobial penetration can be assessed through evaluation of antimicrobial concentrations in various lung compartments, including bronchial mucosal tissue, epithelial lining fluid (ELF), and alveolar macrophages (AM).
Antimicrobial concentrations determined in ELF and alveolar macrophages represent an ideal estimate of concentrations at the site of infection and can be accessed via bronchoalveolar lavage (BAL).
However sampling of antimicrobial concentrations via BAL is not routine in clinical practice due to its complex methodology and poor patient tolerability.
This study will evaluate intrapulmonary and plasma pharmacokinetics of GSK2140944 after single IV dose in adult healthy volunteers.
This is a Phase I, open-label study to evaluate plasma and pulmonary pharmacokinetics following intravenous administration of GSK2140944 in healthy adult participants.
Part A will evaluate the single dose PK profiles.
Part B is optional and will only be conducted if necessary.
Each part will consist of a maximum of 6 cohorts.
In Part A, only 4 of the 6 cohorts will be dosed initially; cohorts 5 and 6 are optional and will only be dosed if additional time-points are necessary to adequately model the pulmonary pharmacokinetic profile.
Přehled studie
Postavení
Dokončeno
Podmínky
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
22
Fáze
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Maryland
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Baltimore, Maryland, Spojené státy, 21225
- GSK Investigational Site
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let až 55 let (Dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, vital signs, electrocardiograms (ECGs), physical examination, and laboratory tests. A participant with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if in the Investigator's judgement the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent. A female participant is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) > 40 milli-international units per milliliter (MlU/ml) and estradiol < 40 picrograms (pg)/ml (<147 picromoles/Liter [pmol/L]) is confirmatory. Male participant with female partners of child-bearing potential must agree to use one of the contraception methods listed as per protocol. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
- Body weight >= 50 kg and Body mass index (BMI) within the range 19 - 31Kilograms/meter^2(kg/m^2) (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria:
- Contraindications to bronchoalveolar lavage including hypercapnia >50 millimeters of mercury (mm Hg), known or suspected intolerability to medications necessary for bronchoscopy, refractory hypoxemia, reactive airway disease or asthma, unstable angina or acute myocardial infarction in the last 6 months, heart failure, and severe hemostatic alterations.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the participant at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
- A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening.
- A screening urinalysis positive for protein or glucose (greater than "trace" findings of protein or glucose).
- A serum creatinine value that is out of the normal range, or an increase of 0.2 milligrams/decilitre (mg/dL) (or 15.25 micromoles/Liters [µmol/L]) in serum creatinine value between screening and Day -1 visit.
- History of photosensitivity to quinolones.
- Unwillingness to commit to avoid excessive exposure to sunlight (or exposure whilst on a tanning bed) which would cause a sunburn reaction from first dose up to and including the follow-up visit.
- History of drug abuse within 6 months of the study or a history of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- The participant has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John's Wort within 14 days prior to the first dose of study medication. By exception, the volunteer may take paracetamol or acetaminophen (<=2 grams/day) up to 48 hours prior to the first dose of study medication. However, the Investigator and GSK study team can review medication on a case by case basis to determine if its use would compromise participant safety or interfere with the study procedures or data interpretation.
- History of sensitivity to any of the study medications, including GSK2140944 and those that may be used in association with the BAL procedure, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Donation of blood in excess of 500 mL within 12 weeks prior to dosing.
- History of tendon rupture.
- History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
- Consumption of red wine, pomegranate, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart Rate, Males <40 and >100 Beat Per Minute (bpm), females <50 and >100 bpm; PR interval <120 and >220 msec; QRS duration <70 and >100 msec; A QT interval corrected for heart rate using the Bazett's formula (QTcB) or Single QT duration corrected for heart rate by Fridericia's formula (QTcF) interval >450 msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). A participant has Bundle Branch Block. Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual participant.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Part A(Cohort1)
Study BTZ116666 has two parts.
Each part will consist of a maximum of 6 cohorts.
Part A will be initiated with 4 initial cohorts/timepoints in order to minimize the number of healthy volunteers that undergo bronchoscopy in this study.
After review of data from Cohorts 1 through 4 of Part A, the study team will determine if additional cohorts are needed to be studied in Part A and/ or if Part B is needed.
If the study team determines that additional cohorts are needed, then only the necessary cohorts in Parts A and/or B will be executed.
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 2 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
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Experimentální: Part A (Cohort2)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 4 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
|
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Experimentální: Part A (Cohort3)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 8 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
|
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Experimentální: Part A (Cohort4)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion over 12 hours x 1 dose
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
|
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Experimentální: Part A (Cohort5)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
|
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Experimentální: Part A (Cohort6)
In Part A, participants will receive GSK2140944 1000 mg intravenous (IV) infusion.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously as a single dose.
|
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Experimentální: Part B (Cohort1)
In Part B, participants will receive GSK2140944 1000 mg IV infusion, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
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A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
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Experimentální: Part B (Cohort2)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
|
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Experimentální: Part B (Cohort3)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
|
|
Experimentální: Part B (Cohort4)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
|
|
Experimentální: Part B (Cohort5)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
|
|
Experimentální: Part B (Cohort6)
In Part B, participants will receive GSK2140944 1000 mg IV infusion over, q12h x 5 doses.
Optional Cohort or Part and will only be used if necessary.
Sampling times are to be determined based on the review of preliminary PK results from prior study parts and/or cohorts.
|
A lyophilized formulation, pale yellow to grayish yellow cake containing 750 mg of GSK2140944 (as free base) per vial, Administered intravenously every 12 hours for 5 doses (3 days).
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Pulmonary pharmacokinetics of GSK2140944 following intravenous single-dose administration.
Časové okno: Day 1, Day 2, Day 3
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Blood samples will be collected assessment of PK parameters including Epithelial Lining Fluid (ELF) and Alveolar Macrophages (AM) (AUC[0- τ]), Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a participant across all treatments (AUC[0-t]), Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
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Day 1, Day 2, Day 3
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Plasma pharmacokinetics of GSK2140944 following intravenous single-dose administration.
Časové okno: Day 1, Day 2, Day 3
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Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
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Day 1, Day 2, Day 3
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Pulmonary pharmacokinetics of GSK2140944 following repeat daily multiple intravenous dose administration.
Časové okno: Day1, Day 2, Day 3, Day 4, Day 5
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Blood samples will be collected assessment of PK parameters including ELF and AM AUC(0- τ)), AUC(0-t), Cmax, tmax, ELF and AM/plasma ratios for GSK2140944 at the early, mid and late dosing interval timepoints, and AUCELF/AUC plasma and AUCAM/AUC plasma ratios, as data permit.
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Day1, Day 2, Day 3, Day 4, Day 5
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Plasma pharmacokinetics of GSK2140944 following repeat daily multiple intravenous dose administration.
Časové okno: Day1, Day 2, Day 3, Day 4, Day 5
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Blood sample will be collected for estimation of relative bioavailability and assessment of PK parameters including maximum observed concentration; Cmax, area under the concentration-time curve from time 0 to time t; AUC (0-t) and area under the concentration-time curve from time 0 to infinity; AUC(0-infinity), Systemic clearance of parent drug (CL), Volume of distribution at steady state of parent drug after intravascular (e.g., IV) administration (Vdss) and Terminal phase half-life (t½).
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Day1, Day 2, Day 3, Day 4, Day 5
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Characterisation of the safety profile of GSK2140944 with adverse events (AEs) following intravenous single-dose administration
Časové okno: Up to study day 15
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AE is defined as Any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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Up to study day 15
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Characterisation of the safety profile of GSK2140944 with chemistry and haematology laboratory values following intravenous single-dose administration
Časové okno: Up to study day 15
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Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)
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Up to study day 15
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Characterisation of the safety profile of GSK140944 electrocardiograms (ECG) following intravenous single-dose administration
Časové okno: Up to study day 15
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Twelve (12)-lead ECGs will be obtained using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, RR and QTcB intervals.
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Up to study day 15
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Characterisation of the safety profile of GSK2140944 with vital signs following intravenous single-dose administration
Časové okno: Up to study day 15
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Vital sign measurements will include systolic and diastolic blood pressure, body temperature, pulse rate.
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Up to study day 15
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Characterisation of the safety profile of GSK2140944 with adverse events (AEs) following repeat daily multiple intravenous dose administration
Časové okno: Up to study day 18
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AE is defined as Any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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Up to study day 18
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Characterisation of the safety profile of GSK2140944 with chemistry and haematology laboratory values following repeat daily multiple intravenous dose administration
Časové okno: Up to study day 18
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Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)
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Up to study day 18
|
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Characterisation of the safety profile of GSK140944 electrocardiograms (ECG) following repeat daily multiple intravenous dose administration
Časové okno: Up to study day 18
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Twelve (12)-lead ECGs will be obtained using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, RR and QTcB intervals.
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Up to study day 18
|
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Characterisation of the safety profile of GSK2140944 with vital signs following repeat daily multiple intravenous dose administration
Časové okno: Up to study day 18
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Vital sign measurements will include systolic and diastolic blood pressure, body temperature, pulse rate.
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Up to study day 18
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
25. září 2013
Primární dokončení (Aktuální)
21. prosince 2013
Dokončení studie (Aktuální)
21. prosince 2013
Termíny zápisu do studia
První předloženo
29. srpna 2013
První předloženo, které splnilo kritéria kontroly kvality
29. srpna 2013
První zveřejněno (Odhad)
4. září 2013
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
15. května 2017
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
12. května 2017
Naposledy ověřeno
1. května 2017
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 116666
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Ano
Popis plánu IPD
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Studijní data/dokumenty
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Formulář komentované zprávy o případu
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Soubor dat jednotlivých účastníků
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Zpráva o klinické studii
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Formulář informovaného souhlasu
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Specifikace datové sady
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Plán statistické analýzy
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Protokol studie
Identifikátor informace: 116666Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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