CompletedNCT01610388Updated Jun 12, 2017

A Study to Investigate the Safety, Tolerability and Pharmacokinetics of Oral and Intravenous GSK1322322 in Healthy Subjects

A Phase 1 interventional study of 500mg IV GSK1322322/placebo and 1000mg oral GSK1322322/placebo in Infections, Bacterial, sponsored by GlaxoSmithKline. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-06-12.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Other

From the registry’s dates

Registered 8 months after the study started (first participant enrolled Sep 2011, registered May 2012).

Phase: Phase 1
Study type: Interventional
Enrollment: 61
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study summary

This first time in human (FTIH) study will be the first administration of GSK1322322 as an intravenous formulation and will investigate safety, tolerability, and pharmacokinetics in healthy subjects. One cohort of subjects will undergo bronchoalveolar lavage (BAL) for determination of GSK1322322 concentrations in lung with simultaneous comparison to plasma concentrations to evaluate drug penetration in the lung. The study will evaluate the absolute bioavailability of an oral tablet formulation as compared to the IV formulation.In addition, Amendment 01 will enable the investigation of an improved IV formulation (GSK1322322J mesylate salt) in an additional repeat dosing cohort and the supra-therapeutic cohort.

Conditions studied

Infections, Bacterial

Browse trials for

Bacterial Infections 658

Keywords

healthy subjects
double-blind
FTIH
dose-escalation
absolute bioavailability
GSK1322322
BAL

In context

Bacterial Infections

658 studies on the registry are indexed under Bacterial Infections; 100 are open to participants now.

This study's enrollment of 61 is below the median of 84 across 405 interventional studies indexed under Bacterial Infections.

Browse Bacterial Infections studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Healthy as determined by a responsible and experienced physician, based on a medical evaluation including [medical history, physical examination, laboratory tests and ECGs. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included at the discretion of the Investigator only if the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
A female subject 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
Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the final follow up visit.
Body weight greater than or equal to 50 kilograms and body mass index (BMI) between 18.5-29.9 (inclusive).
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
QTcB less than 450 millisecond (msec); or QTcB less than 480 msec in subjects with Bundle Branch Block on Screening ECG

Exclusion criteria

Exclusion Criteria:

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Contraindications to bronchoalveolar lavage including hypercapnia greater than 50 mm Hg, refractory hypoxemia, reactive airway disease or asthma, unstable angina or acute myocardial infarction in the last 6 months, heart failure, and severe hemostatic alterations (Cohort C only).
A positive pre-study drug/alcohol screen.
A positive test for HIV antibody.
History of regular alcohol consumption within 6 months of the study
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, and within 5 days following discontinuation of GSK1322322 (for sensitive and narrow therapeutic index CYP3A4 substrates), unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
Use of antacids, H2 blockers, proton pump inhibitors, vitamins, and iron supplements within 7 days prior to the first dose of study medication and for the duration of the trial, including follow-up.
History of sensitivity to any of the study medications, 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.
History of sensitivity to medications used in study, ie Atropine, Midazolam, Fentanyl, Lidocaine, Codeine (Cohort C only) that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
Where participation in the study would result in donation of blood or blood products in excess of 500 milliliters within a 56 day period.
Pregnant females as determined by positive [serum or urine] test at screening or prior to dosing.

Lactating females.

Unwillingness or inability to follow the procedures outlined in the protocol.
Subject is mentally or legally incapacitated.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] 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 less than 45 and greater than 100 beats per minute (bpm) and females less than 50 and greater than 100bpm. PR interval less than 120 and greater than 220msec, QRS duration less than 70 and greater than 120 msec, and QTcB greater than 450msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). 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 (greater than or equal to 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 subject.

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Single group
Masking: Double (Participant, Investigator)
Enrollment: 61 participants (actual)

Study arms

Experimental
Cohort A1
Single dose 60 minute infusion of 500mg IV GSK1322322/placebo followed by BID for 4 days
Drug: 500mg IV GSK1322322/placebo
Experimental
Cohort A2
Single dose 30 minute infusion of 500mg IV GSK1322322/placebo followed by BID for 4 days
Drug: 500mg IV GSK1322322/placebo
Experimental
Cohort B
Initial single 1000mg oral GSK1322322/placebo dose, initial single dose 1000mg IV GSK1322322/placebo followed by BID for 4 days
Drug: 1000mg oral GSK1322322/placebo · Drug: 1000mg IV GSK1322322/placebo
Experimental
Cohort C
Initial single 1500mg oral GSK1322322/placebo dose, initial single dose 1500mg IV GSK1322322/placebo followed by BID for 4 days
Drug: 1500mg oral GSK1322322/placebo dose · Drug: 1500mg IV GSK1322322/placebo
Experimental
Cohort D
Single dose 2000mg IV GSK1322322J/placebo
Drug: 2000mg IV GSK1322322J/placebo
Experimental
Cohort E
Single dose 3000mg IV GSK1322322J/placebo
Drug: 3000mg IV GSK1322322J/placebo
Experimental
Cohort F
1000mg IV GSK1322322J/placebo followed by BID for 4 days
Drug: 1000mg IV GSK1322322J/placebo

Interventions

Drug500mg IV GSK1322322/placebo
500mg IV
Drug1000mg oral GSK1322322/placebo
1000mg oral
Drug1000mg IV GSK1322322/placebo
1000mg IV
Drug1500mg oral GSK1322322/placebo dose
1500mg oral
Drug1500mg IV GSK1322322/placebo
1500mg IV
Drug2000mg IV GSK1322322J/placebo
2000mg IV
Drug3000mg IV GSK1322322J/placebo
3000mg IV
Drug1000mg IV GSK1322322J/placebo
1000mg IV

What researchers measure

Primary outcomes

GSK1322322 safety parameters including the number of subjects with adverse events (AEs)
Time frame: Cohort A up to 14 days; Cohort B and C up to 16 days
GSK1322322 safety parameters including absolute values and changes over time of clinical safety laboratory assessments.
Time frame: Cohort A up to 14 days; Cohort B and C up to 16 days
GSK1322322 safety parameters including the change from baseline in vital signs (blood pressure (BP) and heart rate)
Time frame: Cohort A up to 14 days; Cohort B and C up to 16 days
GSK1322322 safety parameters including change from baseline in electrocardiogram (ECG) parameters
Time frame: Cohort A up to 14 days; Cohort B and C up to 16 days
GSK1322322 pharmacokinetic parameters (PK) after single oral dose, area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)).
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-∞)).
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose aximum observed concentration (Cmax).
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose time of occurrence of Cmax (tmax).
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose mean residence time (MRTpo)
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose apparent clearance after oral administration (CL/F)
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose apparent volume of distribution after oral administration (Vz/F)
Time frame: Cohorts B and C on Day -2
GSK1322322 PK parameters after single oral dose terminal phase half-life (t 1/2).
Time frame: cohort B and C on Day -2
GSK1322322 PK parameters after single IV dose area under the concentration-time curve from zero (pre-dose) to some fixed nominal time (12 hours) (AUC(0-12)).
Time frame: Cohorts A, B, C, D, E on Day 1
GSK1322322 PK parameters after single IV dose area under the concentration-time curve from zero (pre-dose) to some fixed nominal time (24 hours) AUC(0-24)
Time frame: Cohorts A, B, C, D, E on Day 1
GSK1322322 PK parameters after single IV dose AUC(0-t)
Time frame: Cohorts A, B, C, D, E on Day 1
GSK1322322 PK parameters after single IV dose AUC(0-∞).
Time frame: Cohorts A, B, C, D, E on Day 1
GSK1322322 PK parameters after single IV dose Cmax
Time frame: Cohorts A, B, C, D, E on Day 1
GSK1322322 PK parameters after single IV dose mean residence time intravenous (MRTiv)
Time frame: Cohort A, B, C, D, E on Day 1
GSK1322322 PK parameters after single IV dose t1/2
Time frame: Cohort A, B, C, D, E on Day 1
Absolute bioavailability will be determined by comparing oral AUC(0-∞) to IV AUC(0-∞)
Time frame: Cohort B and C on Day -2 and Day 1
MAT of oral tablet will be determined (=MRTpo-MRTiv)
Time frame: Cohort B and C on Day -2 and Day 1
After repeated IV doses, pharmacokinetic parameters including Area under the concentration-time curve over the dosing interval (AUC(0-τ))
Time frame: Cohorts A, B, C on Days 3 - 6
After repeated IV doses, pharmacokinetic parameters including Cmax
Time frame: Cohorts A, B, C on Days 3 - 6
After repeated IV doses, pharmacokinetic parameters including CL
Time frame: Cohorts A, B, C on Days 3 - 6
GSK1322322 concentrations in BAL obtained in epithelial lining fluid (ELF) and alveolar macrophages (AM) as compared to that in plasma
Time frame: Cohort C Day 6

Secondary outcomes

GSK1322322 urine PK parameters: amount excreted (Ae) of unchanged GSK1322322, fraction of the dose excreted in the urine (fe) and renal clearance (CLr) following single dose IV administration from Period 2 and Period 3.
Time frame: cohort B and C on Day 1 and 2
Day 6 GSK1322322 AUC(0-τ) compared to AUC(0-12) on Day 1 to evaluate the accumulation ratio following repeat IV administration of GSK1322322.
Time frame: Cohorts A, B, C Day 6 and Day 1
Day 6 GSK1322322 AUC(0-τ) compared to AUC(0-∞) on Day 1 to evaluate time invariance following repeat IV administration of GSK1322322.
Time frame: Cohorts A, B, C Day 6 and Day 1
GSK1322322 PK parameters: AUC(0-∞) on Day 1 and AUC(0-τ) on Day 6 following IV administration at different doses for the assessment of dose proportionality.
Time frame: Cohorts A, B, C Day1 and 6
Microbiome analysis of stool prior to and after exposure to GSK1322322
Time frame: Cohort A, B,C, D, E single sample predose and single sample post dose
GSK1322322J safety parameters including the number of subjects with adverse events (AEs)
Time frame: Cohort D and E up to 11 days, Cohort F up to 14 days
GSK1322322J safety parameters including absolute values and changes over time of clinical safety laboratory assessments
Time frame: Cohort D and E up to 11 days; Cohort F up to 14 days
GSK1322322J safety parameters including the change from baseline in vital signs (blood pressure (BP) and heart rate)
Time frame: Cohort D and E up to 11 days; Cohort F up to 14 days
GSK1322322J safety parameters including change from baseline in electrocardiogram (ECG) parameters
Time frame: Cohort D and E up to 11 days: Cohort F up to 14 days

Study locations

1 site

GSK Investigational Site
Minneapolis, Minnesota 55404, United States

References and documents

Publications

Naderer OJ, Rodvold KA, Jones LS, Zhu JZ, Bowen CL, Chen L, Dumont E. Penetration of GSK1322322 into epithelial lining fluid and alveolar macrophages as determined by bronchoalveolar lavage. Antimicrob Agents Chemother. 2014;58(1):419-23. doi: 10.1128/AAC.01836-13. Epub 2013 Nov 4. PubMed 24189245 ↗

Individual participant data

Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 12, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01610388
Lead sponsor: GlaxoSmithKline
Responsible party: Sponsor
First posted: Jun 4, 2012
Start date: Sep 13, 2011
Primary completion: Jan 26, 2012
Completion: Jan 26, 2012
Last update: Jun 12, 2017

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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