Infections, BacterialPhase 1NCT01262885
A Randomized, Single Blind, Placebo Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses and Repeat Escalating Oral Doses of GSK2251052 in Healthy Adult Subjects
A Phase 1 study testing GSK2251052 in people with Infections, Bacterial, run by GlaxoSmithKline at 1 site in Australia.
Trial summary
GSK2251052 ((S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride) is a Gram negative antibacterial compound currently in development for the treatment of hospital acquired Gram negative infection (including E. coli, K. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Infections, Bacterial
- What is being tested?
- GSK2251052
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteAustralia
- Study dates
- 7 Oct 2010to 25 Aug 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- AST, ALT, alkaline phosphatase and bilirubin < or = 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 enrollment.
- Male or female between 18 and 65 years of age inclusive, 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) > 40 MlU/ml and estradiol < 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 (~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).
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- 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.
- 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 protocol.
- 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 history of orthostatic hypotension
Trial locations and contacts
1 site in 1 country.
About this study
GSK2251052 ((S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride) is a Gram negative antibacterial compound currently in development for the treatment of hospital acquired Gram negative infection (including E. coli, K. pneumoniae, and Enterobacter spp.) This study will be conducted in two (2) parts, with single oral doses being explored in Part A (500, 1000, and 2000 mg) and repeat oral doses (1000 and 2000 mg, b.i.d.) being explored in Part B. Parts A and B will be single-blind, randomized, placebo-controlled, dose-rising studies in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of oral GSK2251052.
- Conditions
- Infections, Bacterial
- Being tested
- GSK2251052, Placebo
- Keywords
- pharmacokinetics, tolerability, single dose, antibiotics, repeat dose, GSK2251052, safety
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2251052Drug
500 mg tablet, dose levels detailed in Arm description
PlaceboDrug
matching placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Part A Cohort 1 | Experimental | GSK2251052 500 mg (6 subjects), Placebo (1 subject) Receives: Drug: GSK2251052; Drug: Placebo |
| Part A Cohort 2 | Experimental | GSK2251052 1000 mg (6 subjects), Placebo (1 subject) Receives: Drug: GSK2251052; Drug: Placebo |
| Part A Cohort 3 | Experimental | GSK2251052 2000 mg (6 subjects), Placebo (1 subject) Receives: Drug: GSK2251052; Drug: Placebo |
| Part A Cohort 2 - fed | Experimental | GSK2251052 1000 mg (6 subjects), Placebo (1 subject) Receives: Drug: GSK2251052; Drug: Placebo |
| Part B Cohort 1 | Experimental | Placebo (3 subjects), GSK2251052 (9 subjects) dose to be determined Receives: Drug: GSK2251052; Drug: Placebo |
| Part B Cohort 2 | Experimental | Placebo (3 subjects), GSK2251052 (9 subjects) dose to be determined Receives: Drug: GSK2251052; Drug: Placebo |
| Part B Cohort 3 | Experimental | Placebo (3 subjects), GSK2251052 (9 subjects) dose to be determined Receives: Drug: GSK2251052; Drug: Placebo |
| Part A Cohort 4 | Experimental | Placebo (1 subject), GSK2251052 (6 subjects) dose to be determined Receives: Drug: GSK2251052; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event reporting, clinical laboratory tests, vital signs, cardiac monitoring, urinalysis, and clinical monitoring/observation.
Measured: within 35 days of first dose
Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, t1/2, Ae, fe, and CLr of GSK2251052 as data permit.
Measured: within 14 days of first dose
Secondary outcomes (4)
AUC(0-t), AUC(0-inf), and Cmax following single dose administration for the assessment of dose proportionality
Measured: within 72 h of dosing
Trough plasma concentrations
Measured: within 10 days of first dose
Accumulation based on AUC(Ro) and Cmax (RCmax) and determine the steady-state ratio (Rss)
Measured: within 14 days of first dose
AUC(0-t)am and Cmax,am following repeat administration at different doses for the assessment of dose proportionality
Measured: within 14 days of first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2010 (estimated)
- Study start7 Oct 2010
- Primary completion25 Aug 2011
- Study completion25 Aug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infections, BacterialStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 84 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
- NCT01262885
- Sponsor's protocol ID
- 114470
- Status last verified
- Jun 2017
- First submitted
- 16 Dec 2010
- 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 Randomized, Single Blind, Placebo Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses and Repeat Escalating Oral Doses of GSK2251052 in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT01262885
- Acronym / sponsor ID
- 114470
- Conditions
- Infections, Bacterial
- Keywords
- pharmacokinetics, tolerability, single dose, antibiotics, repeat dose, GSK2251052, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 7 Oct 2010 (actual)
- Primary completion
- 25 Aug 2011 (actual)
- Study completion
- 25 Aug 2011 (actual)
- First posted
- 17 Dec 2010 (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 ((S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride) is a Gram negative antibacterial compound currently in development for the treatment of hospital acquired Gram negative infection (including E. coli, K. pneumoniae, and Enterobacter spp.) This study will be conducted in two (2) parts, with single oral doses being explored in Part A (500, 1000, and 2000 mg) and repeat oral doses (1000 and 2000 mg, b.i.d.) being explored in Part B. Parts A and B will be single-blind, randomized, placebo-controlled, dose-rising studies in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of oral GSK2251052.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part A Cohort 1 | Experimental | Drug: GSK2251052, Drug: PlaceboGSK2251052 500 mg (6 subjects), Placebo (1 subject) |
| Part A Cohort 2 | Experimental | Drug: GSK2251052, Drug: PlaceboGSK2251052 1000 mg (6 subjects), Placebo (1 subject) |
| Part A Cohort 3 | Experimental | Drug: GSK2251052, Drug: PlaceboGSK2251052 2000 mg (6 subjects), Placebo (1 subject) |
| Part A Cohort 2 - fed | Experimental | Drug: GSK2251052, Drug: PlaceboGSK2251052 1000 mg (6 subjects), Placebo (1 subject) |
| Part B Cohort 1 | Experimental | Drug: GSK2251052, Drug: PlaceboPlacebo (3 subjects), GSK2251052 (9 subjects) dose to be determined |
| Part B Cohort 2 | Experimental | Drug: GSK2251052, Drug: PlaceboPlacebo (3 subjects), GSK2251052 (9 subjects) dose to be determined |
| Part B Cohort 3 | Experimental | Drug: GSK2251052, Drug: PlaceboPlacebo (3 subjects), GSK2251052 (9 subjects) dose to be determined |
| Part A Cohort 4 | Experimental | Drug: GSK2251052, Drug: PlaceboPlacebo (1 subject), GSK2251052 (6 subjects) dose to be determined |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- AST, ALT, alkaline phosphatase and bilirubin < or = 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 enrollment.
- Male or female between 18 and 65 years of age inclusive, 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 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 (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
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 |
|---|---|---|
| GSK2251052500 mg tablet, dose levels detailed in Arm description | Drug | Part A Cohort 1, Part A Cohort 2, Part A Cohort 2 - fed, Part A Cohort 3, Part A Cohort 4, Part B Cohort 1, Part B Cohort 2, Part B Cohort 3 |
| Placebomatching placebo tablet | Drug | Part A Cohort 1, Part A Cohort 2, Part A Cohort 2 - fed, Part A Cohort 3, Part A Cohort 4, Part B Cohort 1, Part B Cohort 2, Part B Cohort 3 |
Primary outcome
Adverse event reporting, clinical laboratory tests, vital signs, cardiac monitoring, urinalysis, and clinical monitoring/observation.
Time frame: within 35 days of first dose
Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, t1/2, Ae, fe, and CLr of GSK2251052 as data permit.
Time frame: within 14 days of first dose
4 secondary outcomes
AUC(0-t), AUC(0-inf), and Cmax following single dose administration for the assessment of dose proportionality
Time frame: within 72 h of dosing
Trough plasma concentrations
Time frame: within 10 days of first dose
Accumulation based on AUC(Ro) and Cmax (RCmax) and determine the steady-state ratio (Rss)
Time frame: within 14 days of first dose
AUC(0-t)am and Cmax,am following repeat administration at different doses for the assessment of dose proportionality
Time frame: within 14 days of first dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2017.
- Results for study 114470 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 Infections, Bacterial, 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: finished, 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse event reporting, clinical laboratory tests, vital signs, cardiac monitoring, urinalysis, and clinical monitoring/observation. (time frame: within 35 days of first dose). The study lists 2 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; AzTrials last refreshed its copy on 3 Nov 2026.