Infections, Respiratory TractPhase 1NCT01706315

This Study Will Investigate the Safety, Tolerability and Pharmacokinetic Profile of Repeat Oral Doses of GSK2140944 in Healthy Adult Subjects

A Phase 1 study testing GSK2140944 in people with Infections, Respiratory Tract, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Infections, Respiratory Tract
What is being tested?: GSK2140944
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 72 participants
Where: 1 siteUnited States
Study dates: 17 Oct 2012to 13 Dec 2013
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

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x upper limit of normal (ULN) (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 GlaxSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Male or female between 18 and 60 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. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) >40 MlU/ml and estradiol <40 pg/ml (<147 pmol/L) is confirmatory. Male subjects with female partners of child-bearing potential must agree to use the contraception methods. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
Body weight >=50 kg and body mass index (BMI) within the range 19 to 31 kg/m2 (inclusive).
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Who cannot join

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
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.
A screening or Day -2 urinalysis positive for protein or glucose (greater than "trace" findings of protein or glucose).
A serum creatinine value between screening and Day -2 visit that is increased by more than 0.2 mg/dL (or 15.25 umol/L) changes.
History of photosensitivity to quinolones and tendon rupture.

Show all 22Show fewer

Unwillingness to commit to avoid excessive exposure to sunlight which would cause a sunburn reaction from first dose up to and including the follow-up visit.
A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening or Day -2.
History of drug abuse within 6 months of the study
History of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
Use of prescription or non-prescription drugs, including vitamins, 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 paracetamol or acetaminophen (<=2 grams/day) up to 48 hours prior to the first dose of study medication. However, the Investigator and GSK study team can review medication on a case by case basis to determine if its use would compromise subject safety or interfere with the 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.
History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
Donation of blood in excess of 500 ml within 12 weeks prior to dosing.
Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
Screening ECG: Heart rate <40 and >100 bpm for males and <50 and >100 bpm for females. PR Interval <120 and >220 msec, QRS duration <70 and >100 msec, QTcB or QTcF interval >450msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization); any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses >3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject.
Screening holter monitoring shows one or more of the following: any symptomatic arrhythmia (except isolated extra systoles); sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (SVT) [>10 consecutive beats]); sinus tachycardia (or SVT) >150 bpm; non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats); any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher in an awake subject], WPW syndrome, other pre-excitation syndromes); symptomatic sinus pause or sinus pause >3 seconds - unless patient is straining, vomiting, or having some other type of hypervagal response; 300 or more supraventricular ectopic beats in 24 hours; 250 or more ventricular ectopic beats in 24 hours; Ischemia, diagnosed by a sequence of EKG changes that include flat or down sloping ST-segment depression >0.1 mV, with a gradual onset and offset that lasts for a minimum period of 1 minute. Each episode of ischemia must be separated by a minimum duration of at least 1 minute, during which the ST segment returns back to baseline (1x1x1 rule).
Unwillingness or inability to follow the procedures outlined in the protocol.
Subject is mentally or legally incapacitated.
Neutrophil count <2000 cells per microliter (a single repeat is allowed for eligibility determination).

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Overland Park, Kansas, 66211

Other trials in United States

About this study

Official title: A Randomized, Single Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Repeat Escalating Oral Doses of GSK2140944 in Healthy Adult Subjects (BTZ116778)

This will be a randomized, placebo-controlled, single blind study to investigate the safety, tolerability and pharmacokinetic (PK) profile of GSK2140944 following repeat oral doses in healthy adult subjects. The study will include a Screening period (40 days), Treatment period (16 days) and a Follow-up period (26 to 30 days). A single dose will be administered on Day 1 for characterization of single dose PK, followed by twice-daily (BID) or thrice-daily (TID) dosing on Days 3 to 16. Subjects may only be randomized to one cohort per the randomization schedule. Up to 6 cohorts will be enrolled using a sequential panel. Subjects in Cohort 1 will receive GSK2140944 (6) and placebo (2). Subsequent cohorts will enroll 16 subjects such that 12 subjects will receive GSK2140944 and 4 subjects will receive placebo, per dose level according to the randomization schedule. Dose escalations are planned to run in successive weeks. Cohort 2 may begin dosing once subjects in Cohort 1 have completed 7 days of BID dosing, PK data is reviewed and safety data from at least 6 subjects is available. Each subsequent dose escalation will commence only when GSK2140944 safety data and available PK data of at least 12 subjects dosed at the previous dose level have been reviewed. The number of cohorts may be reduced or expanded if needed. The first planned dose is 400 milligram (mg) BID but may be modified based upon emergent PK, safety and tolerability data from ongoing clinical study BTZ115198 evaluating single and repeat intravenous (IV) doses of GSK2140944. The projected dose for Cohort 2 is 800 mg BID, Cohort 3 is 1500 mg BID, Cohort 4 is 2300 mg BID or 1500 mg TID and Cohort 5 and cohort 6 will be decided later. The planned maximum dose is 2500 mg TID but may be modified based upon emergent safety, tolerability and PK data. Doses of GSK2140944 or placebo will be administered following a moderate fat meal.

Conditions: Infections, Respiratory Tract
Being tested: GSK2140944, Placebo
Medical subject headings: Respiratory Tract Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2140944Drug
GSK2140944 will be available as immediate release capsules of dose strength 100 mg and 500 mg
PlaceboDrug
Matching placebo will be available

Study groups in NCT01706315
Study group	Role	What they receive
Cohort 1 - GSK2140944 400 mg	Experimental	Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days Receives: Drug: GSK2140944
Cohort 1 - Placebo	Placebo comparator	Subjects will be randomized in 6:2 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days Receives: Drug: Placebo
Cohort 2 - GSK2140944 800 mg	Experimental	Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 2 will be decided based on the safety and PK data from six subjects in Cohort 1 Receives: Drug: GSK2140944
Cohort 2 - Placebo	Placebo comparator	Subjects will be randomized in 12:4 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days Receives: Drug: Placebo
Cohort 3 - GSK2140944 1500 mg	Experimental	Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 3 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 2 Receives: Drug: GSK2140944
Cohort 3 - Placebo	Placebo comparator	Subjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days Receives: Drug: Placebo
Cohort 4 - GSK2140944 2500 mg	Experimental	Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 4 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 3 Receives: Drug: GSK2140944
Cohort 4 - Placebo	Placebo comparator	Subjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days Receives: Drug: Placebo
Cohort 5 - GSK2140944 TBD	Experimental	Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 4 Receives: Drug: GSK2140944
Cohort 5 - Placebo	Placebo comparator	Subjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days Receives: Drug: Placebo
Cohort 6 - GSK2140944 TBD	Experimental	Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 6 subjects dosed at the Cohort 5 Receives: Drug: GSK2140944
Cohort 6 - Placebo	Placebo comparator	Subjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

GSK2140944 clinical safety data assessed as change from baseline in 12-lead ECG
12-lead ECGs will be obtained at each timepoint using an ECG machine, after the subject has rested in a semi-supine position for at least 10 minutes
Measured: Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and at the Follow-up visit
GSK2140944 clinical safety data from dual-lead cardiac monitoring
Continuous dual-lead cardiac monitoring will be obtained at each timepoints using an ECG machine
Measured: Day 1
GSK2140944 clinical safety data assessed as change from baseline in clinical laboratory tests
Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
Measured: Day -2 and pre-morning dose on Day 2, Day 5, Day 8, Day 11, and Day 14; on the morning of Day 17 and at the Follow-up visit
GSK2140944 clinical safety data assessed as by number of adverse events (AE)
Safety and tolerability parameters will include recording of AEs, throughout the study
Measured: Up to the Follow-up visit
GSK2140944 clinical safety data assessed as change from baseline in blood pressure
Vital sign measurements will be done in semi-supine position and will include systolic and diastolic blood pressure
Measured: Day -1, Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and the Follow-up visit
GSK2140944 clinical safety data assessed as change from baseline in heart rate
Vital sign measurements will be done in semi-supine position and will include pulse rate
Measured: Day -1, Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and the Follow-up visit
Pharmacokinetic parameter: AUC(0-12) following single dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 12 hour post-dose (AUC(0-12)) following single dose of GSK2140944
Measured: Day 1
Pharmacokinetic parameter: AUC(0-24) following single dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 24 hour post-dose (AUC(0-24)) following single dose of GSK2140944
Measured: Up to Day 2
Pharmacokinetic parameter: AUC(0-t) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) following single dose of GSK2140944
Measured: Up to Day 3
Pharmacokinetic parameter: AUC(0-infinity) following single dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)) following single dose of GSK2140944
Measured: Up to Day 3
Pharmacokinetic parameter: Cmax following single dose of GSK2140944
Pharmacokinetic data will include maximum observed concentration (Cmax) following single dose of GSK2140944
Measured: Up to Day 3
Pharmacokinetic parameter: tmax following single dose of GSK2140944
Pharmacokinetic data will include time of occurrence of Cmax (tmax) following single dose of GSK2140944
Measured: Up to Day 3
Pharmacokinetic parameter: t1/2 following single dose of GSK2140944
Pharmacokinetic data will include terminal phase half-life (t1/2) following single dose of GSK2140944
Measured: Up to Day 3
Pharmacokinetic parameter: AUC(0-tau) following repeat dose of GSK2140944
Pharmacokinetic data will include area under the concentration-time curve over the dosing interval (AUC(0-tau)) following repeat dose of GSK2140944
Measured: Day 14, Day 15 and Day 16
Pharmacokinetic parameter: Cmax following repeat dose of GSK2140944
Pharmacokinetic data will include Cmax following repeat dose of GSK2140944
Measured: Day 14, Day 15 and Day 16
Pharmacokinetic parameter: tmax following repeat dose of GSK2140944
Pharmacokinetic data will include tmax following repeat dose of GSK2140944
Measured: Day 14, Day 15 and Day 16
Pharmacokinetic parameter: Ctau following repeat dose of GSK2140944
Pharmacokinetic data will include pre-dose (trough) concentration at the end of the dosing interval (Ctau) following repeat dose of GSK2140944
Measured: Day 14, Day 15 and Day 16
Pharmacokinetic parameter: Ro following repeat dose of GSK2140944
Pharmacokinetic data will include accumulation ratio (Ro) following repeat dose of GSK2140944
Measured: Day 14, Day 15 and Day 16
Pharmacokinetic parameter: AUC(0-8) following single dose of GSK2140944
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 8 hour post-dose (AUC[0-8]) following single dose of GSK2140944
Measured: Day 1

Secondary outcomes (9)

To assess preliminary dose proportionality using PK parameter AUC(0-infinity) following single dose of GSK2140944
Preliminary dose proportionality will be assessed using PK parameter (AUC(0-infinity)) following single dose of GSK2140944
Measured: Up to Day 3
To assess preliminary dose proportionality using PK parameter Cmax following single dose of GSK2140944
Preliminary dose proportionality will be assessed using PK parameter Cmax following single dose of GSK2140944
Measured: Up to Day 3
To assess preliminary dose proportionality using PK parameter AUC(0-tau) following repeat doses of GSK2140944
Preliminary dose proportionality will be assessed using PK parameter (AUC(0-tau) following repeat doses of GSK2140944
Measured: Day 14, Day 15 and Day 16
To assess preliminary dose proportionality using PK parameter Cmax following repeat doses of GSK2140944
Preliminary dose proportionality will be assessed using PK parameter Cmax following repeat doses of GSK2140944
Measured: Day 14, Day 15 and Day 16
To examine extent of accumulation using PK parameter Ro using AUC(0-tau) following repeat doses of GSK2140944
Accumulation ratio will be assessed using PK parameter AUC(0-tau) following repeat doses of GSK2140944
Measured: Day 14, Day 15 and Day 16
To examine extent of accumulation using PK parameter AUC(0-tau) following single dose of GSK2140944
Accumulation ratio will be assessed using PK parameter AUC(0-tau) following single dose of GSK2140944
Measured: Day 1
To examine the extent of time invariance using repeat dose AUC(0-tau)
The extent of time invariance will be assessed using PK parameter AUC(0-tau) following repeat dose
Measured: Day 14, Day 15 and Day 16
To examine the extent of time invariance using single dose AUC(0-infinity)
The extent of time invariance will be assessed using PK parameter AUC(0-infinity) following single dose
Measured: Up to Day 3
To assess achievement of steady-state following repeat oral doses of GSK2140944
Achievement of steady-state will be assessed using trough concentrations at the end of the dosing interval (Ctau) collected at pre-morning dose on Days 14 and 15 (together with pre-morning dose Ctau on Days 16 from the full PK profiles on Day 16).
Measured: Day 14, Day 15 and Day 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Oct 201213 Dec 2013

First posted15 Oct 2012 (estimated)
Study start17 Oct 2012
Primary completion13 Dec 2013
Study completion13 Dec 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infections, Respiratory TractStudies 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: Investigator
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01706315
Sponsor's protocol ID: 116778
Status last verified: May 2017
First submitted: 11 Oct 2012
Last updated: 9 May 2017
Results posted: No
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

Tiffany C, Dumont EF, Hossain M, Srinivasan M, Swift B. Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects. Clin Transl Sci. 2022 Sep;15(9):2251-2264. doi: 10.1111/cts.13359. Epub 2022 Jul 13.
PubMed 35769034

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 May 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 Repeat Escalating Oral Doses of GSK2140944 in Healthy Adult Subjects (BTZ116778)
ClinicalTrials.gov ID: NCT01706315
Acronym / sponsor ID: 116778
Conditions: Infections, Respiratory Tract
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 17 Oct 2012 (actual)
Primary completion: 13 Dec 2013 (actual)
Study completion: 13 Dec 2013 (actual)
First posted: 15 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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 12

Arm	Type	Receives
Cohort 1 - GSK2140944 400 mg	Experimental	Drug: GSK2140944Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days
Cohort 1 - Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 6:2 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days
Cohort 2 - GSK2140944 800 mg	Experimental	Drug: GSK2140944Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 2 will be decided based on the safety and PK data from six subjects in Cohort 1
Cohort 2 - Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 12:4 ratio to receive either GSK2140944 BID or matching placebo for approximately 15 days
Cohort 3 - GSK2140944 1500 mg	Experimental	Drug: GSK2140944Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 3 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 2
Cohort 3 - Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days
Cohort 4 - GSK2140944 2500 mg	Experimental	Drug: GSK2140944Subjects will be randomized in 12:4 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) BID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 4 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 3
Cohort 4 - Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 12:4 ratio to receive either GSK2140944 bid or matching placebo for approximately 15 days
Cohort 5 - GSK2140944 TBD	Experimental	Drug: GSK2140944Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 12 subjects dosed at the Cohort 4
Cohort 5 - Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days
Cohort 6 - GSK2140944 TBD	Experimental	Drug: GSK2140944Subjects will be randomized in 6:2 ratio to receive either GSK2140944 (Day 1: Single oral dose Days 3 to 16: (14 Days) TID oral doses) or placebo for approximately 15 days. GSK2140944 dose in Cohort 5 will be decided on the safety data and available PK data from at least 6 subjects dosed at the Cohort 5
Cohort 6 - Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 6:2 ratio to receive either GSK2140944 TID or matching placebo for approximately 15 days

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x upper limit of normal (ULN) (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 GlaxSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Male or female between 18 and 60 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. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) >40 MlU/ml and estradiol <40 pg/ml (<147 pmol/L) is confirmatory. Male subjects with female partners of child-bearing potential must agree to use the contraception methods. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
Body weight >=50 kg and body mass index (BMI) within the range 19 to 31 kg/m2 (inclusive).

Key exclusion criteria (22 listed)

A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
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.
A screening or Day -2 urinalysis positive for protein or glucose (greater than "trace" findings of protein or glucose).
A serum creatinine value between screening and Day -2 visit that is increased by more than 0.2 mg/dL (or 15.25 umol/L) changes.

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
GSK2140944GSK2140944 will be available as immediate release capsules of dose strength 100 mg and 500 mg	Drug	Cohort 1 - GSK2140944 400 mg, Cohort 2 - GSK2140944 800 mg, Cohort 3 - GSK2140944 1500 mg, Cohort 4 - GSK2140944 2500 mg, Cohort 5 - GSK2140944 TBD, Cohort 6 - GSK2140944 TBD
PlaceboMatching placebo will be available	Drug	Cohort 1 - Placebo, Cohort 2 - Placebo, Cohort 3 - Placebo, Cohort 4 - Placebo, Cohort 5 - Placebo, Cohort 6 - Placebo

Primary outcome

GSK2140944 clinical safety data assessed as change from baseline in 12-lead ECG
Time frame: Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and at the Follow-up visit
12-lead ECGs will be obtained at each timepoint using an ECG machine, after the subject has rested in a semi-supine position for at least 10 minutes
GSK2140944 clinical safety data from dual-lead cardiac monitoring
Time frame: Day 1
Continuous dual-lead cardiac monitoring will be obtained at each timepoints using an ECG machine
GSK2140944 clinical safety data assessed as change from baseline in clinical laboratory tests
Time frame: Day -2 and pre-morning dose on Day 2, Day 5, Day 8, Day 11, and Day 14; on the morning of Day 17 and at the Follow-up visit
Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
GSK2140944 clinical safety data assessed as by number of adverse events (AE)
Time frame: Up to the Follow-up visit
Safety and tolerability parameters will include recording of AEs, throughout the study
GSK2140944 clinical safety data assessed as change from baseline in blood pressure
Time frame: Day -1, Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and the Follow-up visit
Vital sign measurements will be done in semi-supine position and will include systolic and diastolic blood pressure
GSK2140944 clinical safety data assessed as change from baseline in heart rate
Time frame: Day -1, Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and the Follow-up visit
Vital sign measurements will be done in semi-supine position and will include pulse rate
Pharmacokinetic parameter: AUC(0-12) following single dose of GSK2140944
Time frame: Day 1
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 12 hour post-dose (AUC(0-12)) following single dose of GSK2140944
Pharmacokinetic parameter: AUC(0-24) following single dose of GSK2140944
Time frame: Up to Day 2
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 24 hour post-dose (AUC(0-24)) following single dose of GSK2140944
Pharmacokinetic parameter: AUC(0-t) following single dose of GSK2140944
Time frame: Up to Day 3
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) following single dose of GSK2140944
Pharmacokinetic parameter: AUC(0-infinity) following single dose of GSK2140944
Time frame: Up to Day 3
Pharmacokinetic data will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)) following single dose of GSK2140944
Pharmacokinetic parameter: Cmax following single dose of GSK2140944
Time frame: Up to Day 3
Pharmacokinetic data will include maximum observed concentration (Cmax) following single dose of GSK2140944
Pharmacokinetic parameter: tmax following single dose of GSK2140944
Time frame: Up to Day 3
Pharmacokinetic data will include time of occurrence of Cmax (tmax) following single dose of GSK2140944
Pharmacokinetic parameter: t1/2 following single dose of GSK2140944
Time frame: Up to Day 3
Pharmacokinetic data will include terminal phase half-life (t1/2) following single dose of GSK2140944
Pharmacokinetic parameter: AUC(0-tau) following repeat dose of GSK2140944
Time frame: Day 14, Day 15 and Day 16
Pharmacokinetic data will include area under the concentration-time curve over the dosing interval (AUC(0-tau)) following repeat dose of GSK2140944
Pharmacokinetic parameter: Cmax following repeat dose of GSK2140944
Time frame: Day 14, Day 15 and Day 16
Pharmacokinetic data will include Cmax following repeat dose of GSK2140944
Pharmacokinetic parameter: tmax following repeat dose of GSK2140944
Time frame: Day 14, Day 15 and Day 16
Pharmacokinetic data will include tmax following repeat dose of GSK2140944
Pharmacokinetic parameter: Ctau following repeat dose of GSK2140944
Time frame: Day 14, Day 15 and Day 16
Pharmacokinetic data will include pre-dose (trough) concentration at the end of the dosing interval (Ctau) following repeat dose of GSK2140944
Pharmacokinetic parameter: Ro following repeat dose of GSK2140944
Time frame: Day 14, Day 15 and Day 16
Pharmacokinetic data will include accumulation ratio (Ro) following repeat dose of GSK2140944
Pharmacokinetic parameter: AUC(0-8) following single dose of GSK2140944
Time frame: Day 1
Pharmacokinetic data will include area under the curve from time zero (pre-dose) to 8 hour post-dose (AUC[0-8]) following single dose of GSK2140944

9 secondary outcomes

To assess preliminary dose proportionality using PK parameter AUC(0-infinity) following single dose of GSK2140944
Time frame: Up to Day 3
To assess preliminary dose proportionality using PK parameter Cmax following single dose of GSK2140944
Time frame: Up to Day 3
To assess preliminary dose proportionality using PK parameter AUC(0-tau) following repeat doses of GSK2140944
Time frame: Day 14, Day 15 and Day 16
To assess preliminary dose proportionality using PK parameter Cmax following repeat doses of GSK2140944
Time frame: Day 14, Day 15 and Day 16
To examine extent of accumulation using PK parameter Ro using AUC(0-tau) following repeat doses of GSK2140944
Time frame: Day 14, Day 15 and Day 16
To examine extent of accumulation using PK parameter AUC(0-tau) following single dose of GSK2140944
Time frame: Day 1
To examine the extent of time invariance using repeat dose AUC(0-tau)
Time frame: Day 14, Day 15 and Day 16
To examine the extent of time invariance using single dose AUC(0-infinity)
Time frame: Up to Day 3
To assess achievement of steady-state following repeat oral doses of GSK2140944
Time frame: Day 14, Day 15 and Day 16

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 9 May 2017.
Derived from this study: PubMed 35769034Tiffany C, Dumont EF, Hossain M, Srinivasan M, Swift B. Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects. Clin Transl Sci. 2022 Sep;15(9):2251-2264. doi: 10.1111/cts.13359. Epub 2022 Jul 13.
Results for study 116778 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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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 GSK2140944 in people with Infections, Respiratory Tract, run by GlaxoSmithKline at 1 site in United States.

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 6 inclusion and 22 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 9 May 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 United States. 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. Some participants in this study may receive a placebo. 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?

GSK2140944 clinical safety data assessed as change from baseline in 12-lead ECG (time frame: Day 1, Day 4, Day 7, Day 10, Day 13, Day 16, Day 18 and at the Follow-up visit). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01706315, which also lists 1 linked publication.

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 9 May 2017.