Infections, BacterialPhase 1NCT01039610
A Single Center Four Part Study in Healthy Adult Subjects to Evaluate: the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose and Repeat Escalating Oral Doses of GSK945237; the Effect of Linezolid on Hematology Safety Parameters; and the Effects of GSK945237 and Moxifloxacin on QTc.
A Phase 1 study testing GSK945237, Linezolid and Moxifloxacin in people with Infections, Bacterial, run by GlaxoSmithKline.
Trial summary
GSK945237 belongs to the Bacterial Type II Topoisomerase Inhibitor (BTI) class of antibiotics. GSK945237 has demonstrated in vitro and in vivo activity against Gram positive [including methicillin resistant Staphylococcus aureus (MRSA)] and Gram-negative pathogens associated with respiratory tract, skin and soft… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Infections, Bacterial
- What is being tested?
- GSK945237, Linezolid and Moxifloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2009to Aug 2010
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. A subject with a non-clinically significant abnormality or laboratory parameters outside the reference range may be included only if the investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures or data interpretation.
- Male or female between 18 and 60 years of age.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented bilateral tubal ligation, hysterectomy, or bilateral oophorectomy; 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 (<140 pmol/L) is confirmatory].
- Male subjects 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 greater than 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.
- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Who cannot join
- Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
- Any preexisting retinal condition or finding on baseline examination that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial or may interfere with interpretation of ophthalmologic safety results during the conduct of the trial.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
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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 above the recommended daily intake herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John's Wort within 14 days prior to the first dose of study medication. By exception, the volunteer may take acetaminophen (< or equal to 2 grams/day) or ibuprofen (1600 mg/day) up to 48 hours prior to the first dose of study medication. However, the investigator and study team can review medication use on a case by case basis to determine if its use would compromise subject safety or interfere with study procedures or data interpretation.
- 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.
- The subject has donated blood within 2 months prior to dosing and/or donated plasma within 1 week prior to dosing.
- An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women, or an unwillingness of male subjects to use a condom and spermicide, in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if engaging in sexual intercourse with a female partner who could become pregnant. This criterion must be followed from the time of study medication administration and until 90 days after study medication administration.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- 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.
- For Part C and Part D only: Contraindications to the use of linezolid or moxifloxacin, respectively as per the package insert [Avelox Product Information, 2008; Zyvox Product Information, 2008].
About this study
GSK945237 belongs to the Bacterial Type II Topoisomerase Inhibitor (BTI) class of antibiotics. GSK945237 has demonstrated in vitro and in vivo activity against Gram positive [including methicillin resistant Staphylococcus aureus (MRSA)] and Gram-negative pathogens associated with respiratory tract, skin and soft tissue infections including isolates resistant to existing classes of antimicrobials. This study will be conducted in four (4) parts, with a single oral dose being explored in Part A (2400 mg) and repeat oral doses (b.i.d. and q.d.) being explored in Part B. Parts C and D will be optional evaluations of repeat oral doses of linezolid and a comparative evaluation of the effect of GSK945237 and moxifloxacin, respectively. Parts A and B will be single-blind, randomized, placebo-controlled, dose-rising (Part B only) studies of healthy subjects to evaluate the safety, tolerability and pharmacokinetics of GSK945237. The proposed doses range from 400 mg to 2400 mg. Part C will be a single-blind, randomized, and placebo-controlled repeat dose evaluation of 600 mg (b.i.d.) of linezolid. Part D will be a single-blind, randomized, placebo-controlled, two period crossover study. The proposed doses for Part D will be 1200 mg GSK945237 and 400 mg moxifloxacin.
- Conditions
- Infections, Bacterial
- Being tested
- GSK945237, Placebo, Linezolid, Moxifloxacin
- Keywords
- single dose, pharmacokinetics, GSK945237, tolerability, safety, antibiotics, linezolid, QTc, bacterial type II topoisomerase Inhibitors (BTI), moxifloxacin, repeat dose
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK945237Drug
Dose detailed in Arm description
PlaceboDrug
matching placebo tablet
LinezolidDrug
600 mg BID, 14 Days
MoxifloxacinDrug
40 mg single dose
| Study group | Role | What they receive |
|---|---|---|
| Part A | Experimental | GSK945237 2400mg single dose Receives: Drug: GSK945237; Drug: Placebo |
| Part B Cohort 1 | Experimental | GSK945237 400 mg QD, 7 Days 4 subjects GSK945237:2 subjects Placebo Receives: Drug: GSK945237; Drug: Placebo |
| Part B Cohort 2 | Experimental | GSK945237 400 mg QD, 14 Days 4 subjects GSK945237:2 subjects Placebo Receives: Drug: GSK945237; Drug: Placebo |
| Part B Cohort 3 | Experimental | GSK945237 400 mg BID, 14 Days 4 subjects GSK945237:2 subjects Placebo Receives: Drug: GSK945237; Drug: Placebo |
| Part B Cohort 4 | Experimental | GSK945237 800 mg BID, 14 Days 9 subjects GSK945237:3 subjects Placebo Receives: Drug: GSK945237; Drug: Placebo |
| Part B Cohort 5 | Experimental | GSK945237 1200 mg BID, 14 Days 9 subjects GSK945237:3 subjects Placebo Receives: Drug: GSK945237; Drug: Placebo |
| Part B Cohort 6 | Experimental | GS945237 1600 mg QD, 14 Days 9 subjects GSK945237:3 subjects Placebo Receives: Drug: GSK945237; Drug: Placebo |
| Part C | Active comparator | Linezolid 600 mg BID, 14 Days 9 subjects Linezolid:3 subjects Placebo Receives: Drug: Placebo; Drug: Linezolid |
| Part D | Active comparator | 2 period crossover Period 1: Placebo 1 day; GSK945237 dose to be determined, 5 Days Period 2: Placebo 5 days; moxifloxacin 400 mg single dose
16 subjects Receives: Drug: GSK945237; Drug: Placebo; Drug: Moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability assessments, consisting of AEs, ECGs, vital signs, clinical laboratory tests.
Measured: duration of dosing
Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, and t1/2 of GSK945237
Measured: duration of dosing
Amount excreted in urine (Ae) and renal clearance of GSK945237
Measured: duration of dosing
Saliva PK parameters
Measured: duration of dosing
QT interval and heart rate
Measured: duration of dosing
Change from baseline in QTc for GSk945237, moxifloxacin, and placebo
Measured: duration of dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2009 (estimated)
- Study startNov 2009
- Primary completionAug 2010
- Study completionAug 2010 (estimated)
Why it stopped: Internal decision to progress alternate molecule with more preferable profile
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
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 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
- NCT01039610
- Sponsor's protocol ID
- 107895
- Status last verified
- Apr 2015
- First submitted
- 23 Dec 2009
- Last updated
- 22 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center Four Part Study in Healthy Adult Subjects to Evaluate: the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose and Repeat Escalating Oral Doses of GSK945237; the Effect of Linezolid on Hematology Safety Parameters; and the Effects of GSK945237 and Moxifloxacin on QTc.
- ClinicalTrials.gov ID
- NCT01039610
- Acronym / sponsor ID
- 107895
- Conditions
- Infections, Bacterial
- Keywords
- single dose, pharmacokinetics, GSK945237, tolerability, safety, antibiotics, linezolid, QTc
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Internal decision to progress alternate molecule with more preferable profile
- Enrolment
- 0 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (estimated)
- First posted
- 25 Dec 2009 (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.
GSK945237 belongs to the Bacterial Type II Topoisomerase Inhibitor (BTI) class of antibiotics. GSK945237 has demonstrated in vitro and in vivo activity against Gram positive [including methicillin resistant Staphylococcus aureus (MRSA)] and Gram-negative pathogens associated with respiratory tract, skin and soft tissue infections including isolates resistant to existing classes of antimicrobials. This study will be conducted in four (4) parts, with a single oral dose being explored in Part A (2400 mg) and repeat oral doses (b.i.d. and q.d.) being explored in Part B. Parts C and D will be optional evaluations of repeat oral doses of linezolid and a comparative evaluation of the effect of GSK945237 and moxifloxacin, respectively. Parts A and B will be single-blind, randomized, placebo-controlled, dose-rising (Part B only) studies of healthy subjects to evaluate the safety, tolerability and pharmacokinetics of GSK945237. The proposed doses range from 400 mg to 2400 mg. Part C will be a single-blind, randomized, and placebo-controlled repeat dose evaluation of 600 mg (b.i.d.) of linezolid. Part D will be a single-blind, randomized, placebo-controlled, two period crossover study. The proposed doses for Part D will be 1200 mg GSK945237 and 400 mg moxifloxacin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Part A | Experimental | Drug: GSK945237, Drug: PlaceboGSK945237 2400mg single dose |
| Part B Cohort 1 | Experimental | Drug: GSK945237, Drug: PlaceboGSK945237 400 mg QD, 7 Days 4 subjects GSK945237:2 subjects Placebo |
| Part B Cohort 2 | Experimental | Drug: GSK945237, Drug: PlaceboGSK945237 400 mg QD, 14 Days 4 subjects GSK945237:2 subjects Placebo |
| Part B Cohort 3 | Experimental | Drug: GSK945237, Drug: PlaceboGSK945237 400 mg BID, 14 Days 4 subjects GSK945237:2 subjects Placebo |
| Part B Cohort 4 | Experimental | Drug: GSK945237, Drug: PlaceboGSK945237 800 mg BID, 14 Days 9 subjects GSK945237:3 subjects Placebo |
| Part B Cohort 5 | Experimental | Drug: GSK945237, Drug: PlaceboGSK945237 1200 mg BID, 14 Days 9 subjects GSK945237:3 subjects Placebo |
| Part B Cohort 6 | Experimental | Drug: GSK945237, Drug: PlaceboGS945237 1600 mg QD, 14 Days 9 subjects GSK945237:3 subjects Placebo |
| Part C | Active comparator | Drug: Placebo, Drug: LinezolidLinezolid 600 mg BID, 14 Days 9 subjects Linezolid:3 subjects Placebo |
| Part D | Active comparator | Drug: GSK945237, Drug: Placebo, Drug: Moxifloxacin2 period crossover Period 1: Placebo 1 day; GSK945237 dose to be determined, 5 Days Period 2: Placebo 5 days; moxifloxacin 400 mg single dose 16 subjects |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. A subject with a non-clinically significant abnormality or laboratory parameters outside the reference range may be included only if the investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures or data interpretation.
- Male or female between 18 and 60 years of age.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented bilateral tubal ligation, hysterectomy, or bilateral oophorectomy; 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 (<140 pmol/L) is confirmatory].
- Male subjects 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.
Key exclusion criteria (18 listed)
- Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
- Any preexisting retinal condition or finding on baseline examination that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial or may interfere with interpretation of ophthalmologic safety results during the conduct of the trial.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
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 |
|---|---|---|
| GSK945237Dose detailed in Arm description | Drug | Part A, Part B Cohort 1, Part B Cohort 2, Part B Cohort 3, Part B Cohort 4, Part B Cohort 5, Part B Cohort 6, Part D |
| Placebomatching placebo tablet | Drug | Part A, Part B Cohort 1, Part B Cohort 2, Part B Cohort 3, Part B Cohort 4, Part B Cohort 5, Part B Cohort 6, Part C, Part D |
| Linezolid600 mg BID, 14 Days | Drug | Part C |
| Moxifloxacin40 mg single dose | Drug | Part D |
Primary outcome
Safety and tolerability assessments, consisting of AEs, ECGs, vital signs, clinical laboratory tests.
Time frame: duration of dosing
Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, and t1/2 of GSK945237
Time frame: duration of dosing
Amount excreted in urine (Ae) and renal clearance of GSK945237
Time frame: duration of dosing
Saliva PK parameters
Time frame: duration of dosing
QT interval and heart rate
Time frame: duration of dosing
Change from baseline in QTc for GSk945237, moxifloxacin, and placebo
Time frame: duration of dosing
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2015.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK945237, Linezolid and Moxifloxacin in people with Infections, Bacterial, run by GlaxoSmithKline.
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 8 inclusion and 18 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: withdrawn, as of the sponsor's last update on 22 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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?
Safety and tolerability assessments, consisting of AEs, ECGs, vital signs, clinical laboratory tests. (time frame: duration of dosing). The study lists 6 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 22 Apr 2015.