GSK Investigational Site
Baltimore, Maryland, 21225, United States
NCT Number: NCT01934205
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.
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Notify Me18 year–55 year
All sexes
Interventional
Phase 1
Baltimore, Maryland, 21225, United States
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
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).
Time frame: Day 1, Day 2, Day 3
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.
Time frame: Day 1, Day 2, Day 3
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).
Time frame: Day1, Day 2, Day 3, Day 4, Day 5
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.
Time frame: Day1, Day 2, Day 3, Day 4, Day 5
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).
Time frame: Up to study day 15
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.
Time frame: Up to study day 15
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)
Time frame: Up to study day 15
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.
Time frame: Up to study day 15
Vital sign measurements will include systolic and diastolic blood pressure, body temperature, pulse rate.
Time frame: Up to study day 18
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.
Time frame: Up to study day 18
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis)
Time frame: Up to study day 18
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.
Time frame: Up to study day 18
Vital sign measurements will include systolic and diastolic blood pressure, body temperature, pulse rate.
GlaxoSmithKline
Industry
An Open-label Study To Evaluate Plasma and Pulmonary Pharmacokinetics Following Intravenous Administration of GSK2140944 in Healthy Adult Subjects (BTZ116666)
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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