Community-acquired InfectionPhase 1Relative BioNCT01702350
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
A Phase 1 study testing GSK2251052 in people with Community-acquired Infection, run by GlaxoSmithKline at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Community-acquired Infection
- What is being tested?
- GSK2251052
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteAustralia
- Study dates
- 21 Oct 2011to 8 Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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 locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed 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 (including E. coli, K. pneumoniae, and Enterobacter spp.). This is a multi-part study. Part A is a randomized, open-label, single dose, three-period, incomplete block design to evaluate the relative bioavailability of five oral formulations of GSK2251052. Approximately 24 healthy subjects will be enrolled to receive treatment with GSK2251052 at a dose of 2000 mg and randomized to receive three of the following five formulations: 1) enteric-coated tablet (Treatment A), 2) modified release tablet (Treatment B), 3) enteric-coated powder for oral suspension (Treatment C), 4) immediate release tablet (Treatment D), and 5) oral solution (Treatment E). One or two formulations from Part A will be selected on the basis of acceptable safety and pharmacokinetic criteria for further dose evaluation in Part B. If no formulations are deemed to have the desired PK characteristics, Part B will not be conducted. Part B is a randomized, single-blind, placebo-controlled, dose-escalation evaluation of the selected formulation(s) from Part A. Approximately 8 subjects will be randomly assigned to receive GSK2251052 at the planned starting dose of 2000 mg or respective placebo in Period 1. In Period 2, the next dose level will be administered at an increment of 500 mg and/or based on the PK and safety of the preceding period. Additional periods may be conducted with the selected formulation pending acceptable safety in order to achieve target pharmacokinetic concentrations. Part C is a randomized, single-blind, placebo-controlled, two-cohort, two period, crossover study of the selected formulation of GSK2251052 in Part B to evaluate its multiple-dose safety and pharmacokinetics in both young and elderly, male and female healthy volunteers. Approximately 16 subjects will be enrolled (8 per cohort with an equal number of females if possible) and will be randomized to receive either active treatment or placebo for 5 days both fasted and with a meal. Cohorts will be evaluated sequentially, with cohort 1 (young) conducted first, and pending acceptable safety, proceeding with an evaluation in cohort 2 (elderly) subsequently. Part D is identical in design and conduct to Part C except it will evaluate the multipledose pharmacokinetics, safety, and tolerability of an immediate release formulation given thrice daily at a dose of 2000 mg. Part D is conditional and will only be conducted if none of the new formulations demonstrate appropriate pharmacokinetics, safety and tolerability. This study will be conducted at a single center in Australia.
- Conditions
- Community-acquired Infection
- Being tested
- GSK2251052
- Keywords
- Healthy Subjects, Relative Bioavailability, Pharmacokinetics, Elderly Subjects
- Medical subject headings
- Community-Acquired Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2251052Drug
Oral formulation of an an antibacterial
| Study group | Role | What they receive |
|---|---|---|
| Study Drug Formulation A | Experimental | Enterric Coated Tablet Formulation of GSK2251052 Receives: Drug: GSK2251052 |
| Study Drug Formulation B | Experimental | Modified Release Table Formulation of GSK2251052 Receives: Drug: GSK2251052 |
| Study Drug Formulation C | Experimental | Enterric Coated Powder for Oral Suspension Formulation of GSK2251052 Receives: Drug: GSK2251052 |
| Study Drug Formulation D | Experimental | Immidiate Release Table Formulation of GSK2251052 Receives: Drug: GSK2251052 |
| Study Drug Formulation E | Experimental | Oral Solution Formulation of GSk2251052 Receives: Drug: GSK2251052 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Single dose relative bioavailability of five formulations
Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.
Measured: 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.
Measured: 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.
Measured: Days 1 to 4 and day 9
Secondary outcomes (3)
Safety and tolerability in Part A
Clinical safety data from all adverse event reporting, 12-lead ECGs, vital signs, concurrent medication, nursing/physician observation, and safety laboratory tests.
Measured: Days 1 to 4 and day 14 post-dose in periods 3
Safety and tolerability in Part B
Clinical safety data from all adverse event reporting, 12-lead ECGs, vital signs, concurrent medication, nursing/physician observation, and safety laboratory tests.
Measured: 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
Clinical safety data from all adverse event reporting, 12-lead ECGs, vital signs, concurrent medication, nursing/physician observation, and safety laboratory tests.
Measured: Days 1 to 4 and day 9 and day 14 post last dose in period 2.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2012 (estimated)
- Study start21 Oct 2011
- Primary completion8 Dec 2011
- Study completion8 Dec 2011
Why it stopped: Study was terminated in March 2012 due to lack of eficacy in a seperate Phase II study in patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Community-acquired InfectionStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01702350
- Sponsor's protocol ID
- 115244
- Acronym
- Relative Bio
- Status last verified
- Jun 2017
- First submitted
- 20 Sep 2012
- Last updated
- 28 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01702350
- Acronym / sponsor ID
- Relative Bio / 115244
- Conditions
- Community-acquired Infection
- Keywords
- Healthy Subjects, Relative Bioavailability, Pharmacokinetics, Elderly Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated in March 2012 due to lack of eficacy in a seperate Phase II study in patients.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 21 Oct 2011 (actual)
- Primary completion
- 8 Dec 2011 (actual)
- Study completion
- 8 Dec 2011 (actual)
- First posted
- 8 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 (including E. coli, K. pneumoniae, and Enterobacter spp.). This is a multi-part study. Part A is a randomized, open-label, single dose, three-period, incomplete block design to evaluate the relative bioavailability of five oral formulations of GSK2251052. Approximately 24 healthy subjects will be enrolled to receive treatment with GSK2251052 at a dose of 2000 mg and randomized to receive three of the following five formulations: 1) enteric-coated tablet (Treatment A), 2) modified release tablet (Treatment B), 3) enteric-coated powder for oral suspension (Treatment C), 4) immediate release tablet (Treatment D), and 5) oral solution (Treatment E). One or two formulations from Part A will be selected on the basis of acceptable safety and pharmacokinetic criteria for further dose evaluation in Part B. If no formulations are deemed to have the desired PK characteristics, Part B will not be conducted. Part B is a randomized, single-blind, placebo-controlled, dose-escalation evaluation of the selected formulation(s) from Part A. Approximately 8 subjects will be randomly assigned to receive GSK2251052 at the planned starting dose of 2000 mg or respective placebo in Period 1. In Period 2, the next dose level will be administered at an increment of 500 mg and/or based on the PK and safety of the preceding period. Additional periods may be conducted with the selected formulation pending acceptable safety in order to achieve target pharmacokinetic concentrations. Part C is a randomized, single-blind, placebo-controlled, two-cohort, two period, crossover study of the selected formulation of GSK2251052 in Part B to evaluate its multiple-dose safety and pharmacokinetics in both young and elderly, male and female healthy volunteers. Approximately 16 subjects will be enrolled (8 per cohort with an equal number of females if possible) and will be randomized to receive either active treatment or placebo for 5 days both fasted and with a meal. Cohorts will be evaluated sequentially, with cohort 1 (young) conducted first, and pending acceptable safety, proceeding with an evaluation in cohort 2 (elderly) subsequently. Part D is identical in design and conduct to Part C except it will evaluate the multipledose pharmacokinetics, safety, and tolerability of an immediate release formulation given thrice daily at a dose of 2000 mg. Part D is conditional and will only be conducted if none of the new formulations demonstrate appropriate pharmacokinetics, safety and tolerability. This study will be conducted at a single center in Australia.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Study Drug Formulation A | Experimental | Drug: GSK2251052Enterric Coated Tablet Formulation of GSK2251052 |
| Study Drug Formulation B | Experimental | Drug: GSK2251052Modified Release Table Formulation of GSK2251052 |
| Study Drug Formulation C | Experimental | Drug: GSK2251052Enterric Coated Powder for Oral Suspension Formulation of GSK2251052 |
| Study Drug Formulation D | Experimental | Drug: GSK2251052Immidiate Release Table Formulation of GSK2251052 |
| Study Drug Formulation E | Experimental | Drug: GSK2251052Oral Solution Formulation of GSk2251052 |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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:
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2251052Oral formulation of an an antibacterial | Drug | Study Drug Formulation A, Study Drug Formulation B, Study Drug Formulation C, Study Drug Formulation D, Study Drug Formulation E |
Primary outcome
Single dose relative bioavailability of five formulations
Time frame: 3 days
Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.
Pharamacokinetics of escalating single oral doses
Time frame: 4 days
Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.
To evaluate and compare the pharmacokinetics of multiple oral doses of GSK2251052 in young and elderly healthy adult subjects
Time frame: Days 1 to 4 and day 9
Plasma GSK2251052 Cmax, AUC(0-t), AUC(0-Tau), and AUC (0-∞), as applicable, for each formulation.
3 secondary outcomes
Safety and tolerability in Part A
Time frame: Days 1 to 4 and day 14 post-dose in periods 3
Safety and tolerability in Part B
Time frame: 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
Time frame: Days 1 to 4 and day 9 and day 14 post last dose in period 2.
Results and safety
The study was stopped early (reason given: Study was terminated in March 2012 due to lack of eficacy in a seperate Phase II study in patients.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2017.
- Results for study 115244 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2251052 in people with Community-acquired Infection, run by GlaxoSmithKline at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was terminated in March 2012 due to lack of eficacy in a seperate Phase II study in patients.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Single dose relative bioavailability of five formulations (time frame: 3 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2017.