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Infections, BacterialPhase 1NCT02045849

Relative Bioavailability, Safety, Tolerability, Pharmacokinetics (PK) and Food Effect Study of GSK2140944 in Healthy Subjects

A Phase 1 study testing GSK2140944 capsule, GSK2140944 tablet and Itraconazole capsule in people with Infections, Bacterial, 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

This study will be conducted in three parts (Part 1, Part 2 and Part 3). Part 1 of this study will evaluate the relative bioavailability of a single dose of GSK2140944 tablet formulation compared to the reference capsule formulation under fasted conditions. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Infections, Bacterial
What is being tested?
GSK2140944 capsule, GSK2140944 tablet and Itraconazole capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
28 Jan 2014to 21 Aug 2014
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 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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 feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Part 1 and 2: Male or female between 18 and 64 years of age inclusive, at the time of signing the informed consent. Part 3: Male or female subjects at least 65 years of age or older 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 milli-International Units (MIU)/milliliter (mL) and estradiol <40 picograms (pg)/mL (<147 picomoles [pmol]/liter [L]) is confirmatory. Male subjects with female partners of child-bearing potential must agree to use one of 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 kilograms (kg) and body mass index (BMI) within the range 19 - 31 kg/meter square (m^2) (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Alanine amino transferase (ALT), alkaline phosphatase and bilirubin <=1.5xUpper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Who cannot join

  • Criteria Based Upon Medical Histories
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • 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.
  • History of photosensitivity to quinolones.
  • Use of systemic antibiotic within 30 days of screening
  • Previous exposure to GSK2140944
Show all 25Show fewer
  • Confirmed history of C-difficile diarrhea.
  • History of tendon rupture.
  • 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 grams 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.
  • 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).
  • Criteria Based Upon Diagnostic Assessments
  • 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.
  • A screening or Day -1 urinalysis positive for protein or glucose (greater than 1+ findings of protein or glucose).
  • A serum creatinine value that is increased by more than 0.2 milligram (mg)/deciliter (dL) (or 15.25 micromoles/L) between screening and Day -1.
  • For Part 3 Only: Neutrophil count <2000 cells/microliter (a single repeat is allowed for eligibility determination).
  • A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening or at Day -1.
  • Exclusion criteria for screening and baseline ECG (a single repeat is allowed for eligibility determination) as follows: Heart rate: <40 and >100 beats per minute (bpm) for males and <50 and >100 bpm for females; PR Interval: <120 and >220 milliseconds (msec); QRS duration: <70 and >100 msec; QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) interval>450 msec. 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.
  • Other Criteria
  • Donation of blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • 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.
  • Unwillingness to commit to avoid excessive exposure to sunlight (or exposure to a tanning bed) which would cause a sunburn reaction from first dose up to and including the follow-up visit.

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 Single-Center, Three-Part, Open Label Study to Evaluate the Relative Bioavailability of Two Formulations, Food Effect, and Interaction With Itraconazole Following Single Dose of GSK2140944 in Healthy Subjects and Effect of Food on Safety, Tolerability, and Pharmacokinetics Following Multiple Doses of GSK2140944 in Healthy Elderly Subjects

This study will be conducted in three parts (Part 1, Part 2 and Part 3). Part 1 of this study will evaluate the relative bioavailability of a single dose of GSK2140944 tablet formulation compared to the reference capsule formulation under fasted conditions. The effect of food on the pharmacokinetics (PK) of a single dose of the tablet formulation will also be assessed. Part 2 will evaluate the effect of repeat doses of itraconazole on the pharmacokinetics of GSK2140944 following a single dose. A decision will be made whether to use the current capsule formulation or the new tablet formulation in Part 2 based upon the safety and PK data obtained from Part 1. Part 3 is conditionally based upon progression of the tablet formulation from Part 1 and will evaluate the effect of food on the safety, tolerability, and pharmacokinetics of the tablet formulation following multiple doses in elderly healthy subjects.

Being tested
GSK2140944 capsule, GSK2140944 tablet, Itraconazole capsule
Keywords
pharmacokinetics, GSK2140944, tolerability, drug interaction, safety, itraconazole, elderly healthy subjects, food effect, relative bioavailability
Medical subject headings
Bacterial Infections

What participants receive

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

  • GSK2140944 capsuleDrug

    Immediate release capsule containing GSK2140944 and inactive formulation excipients with a unit dose strength of 500 mg

  • GSK2140944 tabletDrug

    Immediate release tablet containing GSK2140944 and inactive formulation excipients with a unit dose strength of 750 mg

  • Itraconazole capsuleDrug

    Capsule containing Itraconazole with a unit dose strength of 100 mg

Study groups in NCT02045849
Study groupRoleWhat they receive
Part 1ExperimentalSubjects will receive either GSK2140944 1500 mg (500 mg x 3) capsules under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fed conditions as per the randomization schedule in each of the three periods with a washout period of at least 3 days between the doses. There will also be a follow-up visit within 5-7 days after the last dose of study drug.
Receives: Drug: GSK2140944 capsule; Drug: GSK2140944 tablet
Part 2ExperimentalSubjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) on Day 1 followed by a repeat dose of Itraconazole 200 mg once daily for 6 days from Day 4 to Day 9. On Day 7, subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) one hour after the dose of Itraconazole. There will also be a follow-up visit within 5-7 days after the last dose of study drug.
Receives: Drug: GSK2140944 capsule; Drug: GSK2140944 tablet; Drug: Itraconazole capsule
Part 3ExperimentalSubjects in Group 1 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fasting and fed conditions in Period I and Period II, respectively. Subjects in Group 2 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fed and fasting conditions in Period I and Period II, respectively. There will be a washout of at least 7 days between the periods. Subjects will have a follow up visit 5-7 days after the last dose of study drug in both the groups.
Receives: Drug: GSK2140944 tablet

What is being measured

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

  1. Part 1: Composite of PK parameters following GSK2140944 administration in fasted and fed state

    PK parameters will include area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time AUC(0-infinity), AUC from time zero to last quantifiable concentration AUC(0-t), relative bioavailability of drug (Frel), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), lag time before observation of drug concentration (tlag) and terminal phase half-life (t1/2) in the fasted state; AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax after moderate fat meal.

    Measured: Day 1 (Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h)

  2. Part 2: Composite of PK parameters of GSK2140944 following repeat oral dosing of itraconazole

    PK parameters will include AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax of GSK2140944.

    Measured: Day 1 and Day 7 (Predose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and 48h post dose and also at 60h and 72h post dose on Day 7

  3. Part 3: Safety and tolerability of GSK2140944 as assessed by adverse events (AEs)

    Measured: Approximately 8 weeks

  4. Part 3: Safety and tolerability of GSK2140944 as assessed by review of concomitant medications

    Measured: Approximately 8 weeks

  5. Part 3: Safety and tolerability of GSK2140944 by laboratory assessments

    Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters

    Measured: Approximately 8 weeks

  6. Part 3: Safety and tolerability of GSK2140944 as assessed by 12-lead electrocardiograms (ECGs)

    All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes

    Measured: Approximately 8 weeks

  7. Part 3: Safety and tolerability of GSK2140944 as assessed by vital signs

    Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature

    Measured: Approximately 8 weeks

Secondary outcomes (10)

  1. Part 1: Safety and tolerability of GSK2140944 as assessed by AEs

    Measured: Approximately 7 weeks

  2. Part 1: Safety and tolerability of GSK2140944 as assessed by review of concomitant medications

    Measured: Approximately 7 weeks

  3. Part 1: Safety and tolerability of GSK2140944 by laboratory assessments

    Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters

    Measured: Approximately 7 weeks

  4. Part 1: Safety and tolerability of GSK2140944 as assessed by 12-lead ECGs

    All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes

    Measured: Approximately 7 weeks

  5. Part 1: Safety and tolerability of GSK2140944 as assessed by vital signs

    Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature

    Measured: Approximately 7 weeks

  6. Part 2: Safety and tolerability of GSK2140944 as assessed by AEs

    Measured: Approximately 6 weeks

  7. Part 2: Safety and tolerability of GSK2140944 by laboratory assessments

    Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters

    Measured: Approximately 6 weeks

  8. Part 2: Safety and tolerability of GSK2140944 as assessed by 12-lead ECGs

    All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes

    Measured: Approximately 6 weeks

  9. Part 2: Safety and tolerability of GSK2140944 as assessed by vital signs

    Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature

    Measured: Approximately 6 weeks

  10. Part 3: Composite of PK parameters of GSK2140944 following repeat oral dosing of GSK2140944

    PK parameters will include AUC over the dosing interval (0-tau), tmax, tlag, t1/2, pre-dose (trough) concentration at the end of the dosing interval (Ctau) and Cmax of GSK2140944

    Measured: Day 3 and Day 4 (Pre-dose), Day 5 (Predose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h)

Timeline

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

  1. First posted27 Jan 2014 (estimated)
  2. Study start28 Jan 2014
  3. Primary completion21 Aug 2014
  4. Study completion21 Aug 2014

Resources

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
Crossover
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02045849
Sponsor's protocol ID
117349
Status last verified
Jul 2017
First submitted
23 Jan 2014
Last updated
13 Jul 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2140944 capsule, GSK2140944 tablet and Itraconazole capsule in people with Infections, Bacterial, 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 25 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 13 Jul 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. 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?

Part 1: Composite of PK parameters following GSK2140944 administration in fasted and fed state (time frame: Day 1 (Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h)). The study lists 7 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 NCT02045849, 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 13 Jul 2017.

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