Last updated: 11/03/2018 17:45:04
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 studyRelative Bio
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: A study to evaluate the relative bioavailability of five different oral formulations of GSK2251052 and the multiple-dose, safety, tolerability, and pharmacokinetics of GSK2251052 with and without food in male and female, young and elderly healthy volunteers
Trial description: 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.
Primary purpose:
Other
Trial design:
Parallel Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
Single dose relative bioavailability of five formulations
Timeframe: 3 days
Pharamacokinetics of escalating single oral doses
Timeframe: 4 days
To evaluate and compare the pharmacokinetics of multiple oral doses of GSK2251052 in young and elderly healthy adult subjects
Timeframe: Days 1 to 4 and day 9
Secondary outcomes:
Safety and tolerability in Part A
Timeframe: Days 1 to 4 and day 14 post-dose in periods 3
Safety and tolerability in Part B
Timeframe: 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
Timeframe: Days 1 to 4 and day 9 and day 14 post last dose in period 2.
Interventions:
Enrollment:
24
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Community-Acquired Infection
Product
epetraborole
Collaborators
Not applicable
Study date(s)
October 2011 to December 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 64 years
Accepts healthy volunteers
Yes
- AST, ALT, alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
- Abnormal LFT tests may be repeated once at the discretion of the Investigator. If an abnormality is repeated, the subject would not be eligible for inclusion.
- 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).
Inclusion and exclusion criteria
Inclusion criteria:
- AST, ALT, alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
- Abnormal LFT tests may be repeated once at the discretion of the Investigator. If an abnormality is repeated, the subject would not be eligible for inclusion.
- 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.
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).
- 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.
- Subjects who have asthma or a history of asthma, (e.g., for any FTIH where risk of bronchoconstriction is unknown, or compound specific where risk of bronchoconstriction).
- 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.
- A recent history of symptomatic orthostatic hypotension.
Trial location(s)
Location
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Other
Actual primary completion date
Not applicable
Actual study completion date
2011-08-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 115244 can be found on the GSK Clinical Study Register.
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