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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01663389
First received: July 19, 2012
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Infections, Bacterial
Drug: GSK1322322 1000 mg containing radioactive 14C-GSK1322322
Drug: GSK1322322 1200 mg containing radioactive 14C-GSK1322322
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 1 through Day 8 of Period 1 and Period 2 (16 days) ] [ Designated as safety issue: No ]
    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.

  • Percent total recovery of radioactivity in urine and feces in each interval and cumulative [ Time Frame: Day 1 through Day 8 (and additional days, if required) of Period 1 and Period 2 (16 days or more) ] [ Designated as safety issue: No ]
    Total recovery of radioactivity in urine and feces (as a percentage of total radioactive dose in each interval and cumulative)


Secondary Outcome Measures:
  • Safety parameters including adverse events, clinical laboratory tests, concomitant medications, electrocardiograms, and vital signs [ Time Frame: Duration of the study (56 days) ] [ Designated as safety issue: No ]
    To evaluate the safety and tolerability of GSK1322322 after single IV and oral solution doses in healthy subjects safety parameters will be analyzed.


Enrollment: 5
Study Start Date: August 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   30 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663389

Locations
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01663389     History of Changes
Other Study ID Numbers: 112167
Study First Received: July 19, 2012
Last Updated: November 8, 2012
Health Authority: United States: Food and Drug Administartion

Keywords provided by GlaxoSmithKline:
mass balance
radiolabel
oral
IV
GSK1322322
healthy volunteer
antibiotic

Additional relevant MeSH terms:
Bacterial Infections

ClinicalTrials.gov processed this record on October 19, 2014