A Four Part Study to Investigate Relative Bioavailability, Safety and Tolerability of up to 5 Oral Formulation of GSK2251052 in Order to Identify a Formulation for Further Evaluation in a Future Later Phase Study

NCT01702350 | Terminated Phase 1

• 1 other identifier: 115244
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

GSK2251052 is a member of a novel mechanistic and structural class of antibiotics that inhibits the bacterial enzyme leucyl tRNA synthetase (LeuRS) by forming a boron adduct with tRNA and is currently in development for the treatment of hospital acquired Gramnegative infections.

Conditions

Community-acquired Infection

Keywords

Healthy Subjects; Relative Bioavailability; Pharmacokinetics; Elderly Subjects

Outcome Measures

Primary Outcomes (3)

• Single dose relative bioavailability of five formulations

  Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.

  3 days

• Pharamacokinetics of escalating single oral doses

  Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.

  4 days

• To evaluate and compare the pharmacokinetics of multiple oral doses of GSK2251052 in young and elderly healthy adult subjects

  Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.

  Days 1 to 4 and day 9

Secondary Outcomes (3)

• Safety and tolerability in Part A

  Days 1 to 4 and day 14 post-dose in periods 3

• Safety and tolerability in Part B

  Days 1 to4 and day 14 post dose in period 3

• Part C and Part D, to assess the safety and tolerability of GSK2251502 in healthy young and elderly volunteers following single and repeat dose administration with and without food

  Days 1 to 4 and day 9 and day 14 post last dose in period 2.

Study Arms (5)

Study Drug Formulation A

EXPERIMENTAL

Enterric Coated Tablet Formulation of GSK2251052

Drug: GSK2251052

Study Drug Formulation B

EXPERIMENTAL

Modified Release Table Formulation of GSK2251052

Drug: GSK2251052

Study Drug Formulation C

EXPERIMENTAL

Enterric Coated Powder for Oral Suspension Formulation of GSK2251052

Drug: GSK2251052

Study Drug Formulation D

EXPERIMENTAL

Immidiate Release Table Formulation of GSK2251052

Drug: GSK2251052

Study Drug Formulation E

EXPERIMENTAL

Oral Solution Formulation of GSk2251052

Drug: GSK2251052

Interventions

GSK2251052 DRUG

Oral formulation of an an antibacterial

Study Drug Formulation A; Study Drug Formulation B; Study Drug Formulation C; Study Drug Formulation D; Study Drug Formulation E

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• AST, ALT, alkaline phosphatase and bilirubin ≤1.5xULN (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, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with coagulation, reticulocyte, or Hgb values outside the normal range should always be excluded from enrolment.
• Part A, Part B, and young healthy cohort in Parts C and D: Male or female between 18 and 64 years of age inclusive, at the time of signing the informed consent. Part C and Part D for healthy elderly cohorts: Male or female ≥65 years of age 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH greater than 40 MlU/ml and estradiol less than 40 pg/ml (\<147 pmol/L) is confirmatory).
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until at least 90 days post-last dose.
• Body weight ≥50 kg and BMI within the range 19 - 32 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• QTc, QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.

You may not qualify if:

• 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).
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• History of regular alcohol consumption within 6 months of the study defined as:
• an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (appromimately 240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• 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) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. However, in elderly cohorts of Part C and Part D, use of concomitant medications may be considered on a case by case basis by the PI in consultation with the GSK Medical monitor.
• 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing..
• Lactating females.
• Unwillingness or inability to follow the procedures outlined in the protocol14. Subject is mentally or legally incapacitated.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

Related Links

• Results for study 115244 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Community-Acquired Infections

Interventions

3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole

Condition Hierarchy (Ancestors)

Infections

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2012
• First Posted: October 8, 2012
• Study Start: October 21, 2011
• Primary Completion: December 8, 2011
• Study Completion: December 8, 2011
• Last Updated: June 28, 2017

Record last verified: 2017-06

Locations

AU (1)