A Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C -GSK1322322 After an Intravenous and an Oral Dose

An Open Label, Non-Randomized, Single Dose, Two Period, Cross-Over, Mass Balance Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C -GSK1322322 Administered as a Single Intravenous and Single Oral Dose to Healthy Adult Male Subjects

This is a phase 1, non-randomized, open label, single-dose, two-period, cross-over study. This study will utilize 14C radiolabeled GSK1322322 to investigate the recovery, excretion, and pharmacokinetics of GSK1322322 in 6 healthy adult male subjects through the sampling of blood, urine, and feces.

Each subject will participate in the study for approximately 7 to 8 weeks i.e., 30 day screening period, two dosing periods (approximately 8 days each) and a follow up visit.

The subjects will be admitted to the clinical unit on Day 1 of the first treatment period and remain in the unit for up to approximately 16 days through the end of the second treatment period.

On Day 1 of Period 1, each subject will receive 14C radiolabeled GSK1322322 as a single therapeutic intravenous (IV) dose (1000 milligrams [mg]). When the total radioactivity is <1% of the administered dose in all subjects, Period 2 dosing will begin (approximately 8 days after the IV dose). On Day 1 of Period 2, each subject will receive single therapeutic oral solution dose (1200 mg). Blood, urine, bile and fecal samples will be collected during both the periods. The subject may be discharged from the unit as early as Day 8 of Period 2. Subjects will visit the study unit for the follow-up visit 7 to 10 days following discharge from the unit.

Study Overview

• Status: Completed
• Conditions: Infections, Bacterial
• Intervention / Treatment: Drug: GSK1322322 1000 mg containing radioactive 14C-GSK1322322; Drug: GSK1322322 1200 mg containing radioactive 14C-GSK1322322

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects between 30 and 55 years of age, with body weight between 60 to 80 kilograms (kg) and a history of regular bowel movements
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods from first dose of study medication until the final follow up visit
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin =<1.5x upper limit of normal
• QT interval by Bazett's correction formula (QTcB) <450 millisecond (msec); or QTcB <480 msec in subjects with Bundle Branch Block
• Available to complete the study and return for follow-up visits if necessary
• Capable of giving written informed consent

Exclusion Criteria:

• Any condition that could interfere with the accurate assessment and recovery of radioactivity [14C]
• Participation in a clinical trial involving administration of radiolabeled 14C-labelled compound(s) within the last 12 months
• Any condition which impairs the absorption, distribution, metabolism or excretion of the investigational product
• Subjects with a history of cholecystectomy
• Subject has received a total body radiation dose of greater than 5.0 millisievert (mSv) or exposure to significant radiation during 1 year before dosing
• The subject has a positive: drug/alcohol, Hepatitis, HIV screen
• Abuse of alcohol
• History of liver disease, or known hepatic or biliary abnormalities
• The subject has recently received an investigational product
• Donation of more than 500 mL blood within a 56 day period
• Unwillingness or inability to follow the procedures outlined in the protocol
• Use of prescription or non-prescription drugs
• Subject is mentally or legally incapacitated
• History of sensitivity to heparin or heparin-induced thrombocytopenia
• Smoking or history or regular use of tobacco or nicotine-containing products
• Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose
• History of cardiac disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK1322322 1000 mg IV; On Day 1 of Period 1, after an overnight fast, subjects will receive GSK1322322 1000 mg IV single dose (containing approximately 45.5 microcurie [μCi] radioactive 14C-GSK1322322) for intravenous infusion over 60 minutes.	Drug: GSK1322322 1000 mg containing radioactive 14C-GSK1322322; GSK1322322 1000 mg is a mesylate salt powder for injection containing 45.5 μCi radioactive 14C-GSK1322322 1000 mg as free base.
Experimental: GSK1322322 1200 mg Oral Solution; On Day 1 of Period 2, after an overnight fast, subjects will receive GSK1322322 1200 mg oral solution single dose (containing approximately 54.5 μCi radioactive 14C-GSK1322322).	Drug: GSK1322322 1200 mg containing radioactive 14C-GSK1322322; GSK1322322 1200 mg is a mesylate salt powder for oral solution containing 54.5 μCi radioactive 14C-GSK1322322 1200 mg as free base.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetic (PK) parameters of GSK1322322 and radiolabeled compound following single IV or oral solution dose: AUC(0-infinity), AUC(0-t), Cmax, tmax, t1/2 for IV and oral solution regimens and CL and Vss for IV regimen only	Plasma PK parameters will be statistically summarized by treatment. Plasma concentration-time data will be analyzed by non-compartmental methods. Following PK parameters will be studied: Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)], AUC(0-t), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2) for IV and oral solution regimens and systemic clearance (CL) and volume of distribution (Vss) for IV regimen only.	Day 1 through Day 8 of Period 1 and Period 2 (16 days)
Percent total recovery of radioactivity in urine and feces in each interval and cumulative	Total recovery of radioactivity in urine and feces (as a percentage of total radioactive dose in each interval and cumulative)	Day 1 through Day 8 (and additional days, if required) of Period 1 and Period 2 (16 days or more)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety parameters including adverse events, clinical laboratory tests, concomitant medications, electrocardiograms, and vital signs	To evaluate the safety and tolerability of GSK1322322 after single IV and oral solution doses in healthy subjects safety parameters will be analyzed.	Duration of the study (56 days)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2012
• Primary Completion (Actual): October 5, 2012
• Study Completion (Actual): October 5, 2012

Study Registration Dates

• First Submitted: July 19, 2012
• First Submitted That Met QC Criteria: August 9, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: healthy volunteer; antibiotic; oral; mass balance; IV; GSK1322322; radiolabel
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: 112167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 112167
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register