Infections, BacterialPhase 2NCT03568942
Pharmacokinetic Study of Oral Gepotidacin (GSK2140944) in Subjects With Uncomplicated Urinary Tract Infection (Acute Cystitis)
A Phase 2 study testing Gepotidacin in people with Infections, Bacterial, run by GlaxoSmithKline at 1 site in United States.
Trial summary
Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor that is being developed for the treatment of uncomplicated urinary tract infections (UTIs; acute cystitis). Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Infections, Bacterial
- What is being tested?
- Gepotidacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jul 2018to 7 Jan 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be >=18 to <=65 years of age inclusive, at the time of signing the informed consent.
- The subject has 2 or more of the following clinical signs and symptoms of acute cystitis with onset <=72 hours of the screening assessment: dysuria, frequency, urgency, or lower abdominal pain.
- The subject has pyuria (>=10 white blood cells per cubic millimeters [WBC/mm^3] or the presence of leukocyte esterase) and/or nitrite from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
- The subject is female. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance from the Baseline Visit through completion of the Test of Cure (TOC) Visit.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Who cannot join
- The subject resides in a nursing home or dependent care-type facility.
- The subject has a body mass index >=40.0 kilogram per square meter (kg/m^2) or a body mass index >=35.0 kg/m^2 with obesity-related health conditions such as high blood pressure or uncontrolled diabetes.
- The subject has a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation.
- The subject is immunocompromised or has altered immune defenses that may predispose the subject to a higher risk of treatment failure and/or complications (e.g., renal transplant recipients, subjects with clinically significant persistent granulocytopenia [absolute neutrophil count <1000/microliter (µL)], and subjects receiving immunosuppressive therapy, including corticosteroid therapy [>40 mg/day prednisolone or equivalent for >1 week or >=20 milligrams per day (mg/day) prednisolone or equivalent for >6 weeks; or prednisolone or equivalent >=10 mg/day for >6 weeks]). Subjects with a known cluster of differentiation 4 (CD4) count of <200 cells/mm^3 should not be enrolled.
- The subject has uncontrolled diabetes, defined as a non-fasting glucose value >300 milligrams per deciliter (mg/dL) or based on investigator judgment.
- The subject has any of the following: A medical condition that requires medication that may be aggravated by inhibition of acetylcholinesterase, such as: a) Poorly controlled asthma or chronic obstructive pulmonary disease at Baseline and, in the opinion of the investigator, not stable on current therapy; b) Acute severe pain, uncontrolled with conventional medical management; c) Active peptic ulcer disease; d) Parkinson disease; e) Myasthenia gravis; f) A history of seizure disorder requiring medications for control (this does not include a history of childhood febrile seizures) OR Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug (e.g., ileostomy or malabsorption syndrome). Subjects who have had a gastric bypass or a cholecystectomy are excluded from the study OR Hemoglobin value <12 grams per deciliter (g/dL) or a known uncorrected iron deficiency.
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- The subject, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.
- The subject has a serious underlying disease that could be imminently life threatening, or the subject is unlikely to survive for the duration of the study period.
- The subject has acute cystitis that is known or suspected to be due to fungal, parasitic, or viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or Enterobacteriaceae (other than Escherichia coli [E. coli]) as the contributing pathogen.
- The subject has symptoms known or suspected to be caused by another disease process such as asymptomatic bacteriuria or chronic interstitial cystitis.
- The subject has an anatomical or physiological anomaly that predisposes the subject to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction or stricture of the urinary tract, primary renal disease (e.g., polycystic renal disease), or neurogenic bladder, or the subject has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesico-ureteral reflux, detrusor insufficiency).
- The subject has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
- The subject who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptoms onset >=96 hours before the Screening assessment, or a temperature >=101 degree Fahrenheit, flank pain, chills, or any other manifestations suggestive of upper UTI.
- The subject has anuria, oliguria, or significant impairment of renal function (creatinine clearance <30 milliliters per minute [mL/min] or clinically significant elevated serum creatinine).
- The subject presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
- The subject has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
- The subject has uncompensated heart failure, defined as New York Heart Association Class >=III.
- The subject has severe left ventricular hypertrophy.
- The subject has a family history of QT prolongation or sudden death.
- The subject has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or bradyarrhythmia within the last 12 months.
- The subject is taking QT-prolonging drugs or drugs known to increase the risk of torsades de points (TdP) per the www.crediblemeds.org "Known Risk of TdP" category at the time of her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the subject is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor or a strong P-glycoprotein (P-gp) inhibitor.
- The subject has a QT interval corrected for heart rate (QTc) >450 milliseconds (msec) or a QTc >480 msec for subjects with bundle-branch block.
- The subject has a known ALT value >2 times upper limit of normal (ULN).
- The subject has a known bilirubin value >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- The subject has a current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), including symptomatic viral hepatitis or moderate-to-severe liver insufficiency (Child Pugh class B or C).
- The subject has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
- The subject must agree not to use the medications or nondrug therapies from the Baseline Visit through the TOC Visit.
- The subject has been previously enrolled in this study or has previously been treated with gepotidacin.
- The subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa Single-Center, Open-Label Study Evaluating the Pharmacokinetics of Repeat Oral Doses of Gepotidacin (GSK2140944) in Adult Female Participants With Uncomplicated Urinary Tract Infection (Acute Cystitis)
Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor that is being developed for the treatment of uncomplicated urinary tract infections (UTIs; acute cystitis). This Phase IIa study will evaluate plasma and urine pharmacokinetics of gepotidacin in female subjects with acute cystitis. Eligible female subjects will receive twice daily (BID) dose of gepotidacin 1500 milligram (mg) for 5 days via oral route. Pre-treatment and post-treatment samples for pharmacokinetic (PK) assessments will be collected throughout the study. The total duration of the study is approximately 28 days.
- Conditions
- Infections, Bacterial
- Being tested
- Gepotidacin
- Keywords
- gepotidacin, GSK2140944, acute cystitis, pharmacokinetics, urinary tract infections
- Medical subject headings
- Bacterial Infections, Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GepotidacinDrug
Gepotidacin tablets will be available at a dose strength of 750 mg. Tablets will be administered BID with water after consumption of food.
| Study group | Role | What they receive |
|---|---|---|
| Female subjects with acute cystitis | Experimental | Adult female subjects with suspected acute cystitis based on clinical presentation and pyuria (>=10 WBC/mm^3 or presence of leukocyte esterase) and/or nitrite will be included. Subjects will be administered 1500 mg gepotidacin BID for 5 days via the oral route. Receives: Drug: Gepotidacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-time Curve (AUC) From Zero (Pre-dose) Over the Dosing Interval (AUC[0-tau]) of Gepotidacin
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population consisted of all participants who received gepotidacin 1500 mg BID through the completion of all PK collections for whom valid and evaluable plasma PK parameters were derived for gepotidacin.
Measured: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Maximum Plasma Concentration (Cmax) of Gepotidacin
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Time of Occurrence of Cmax (Tmax) of Gepotidacin
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Apparent Steady State Clearance (CLss/F) of Gepotidacin
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. CLss/F was calculated as Dose divided by AUC(0-tau).
Measured: Day 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Accumulation Ratio (Ro) of Gepotidacin
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Accumulation ratio (Ro) was calculated as ratio of AUC(0-tau) at Day 4 to AUC(0-tau) at Day 1.
Measured: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Plasma Pre-dose Concentration (Ctau) of Gepotidacin
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 to 5: Pre-dose
Secondary outcomes (26)
Amount of Drug Excreted Over 12 Hours (Ae12hours) of Gepotidacin
Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Ae12hours was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Measured: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
Ae(t1-t2) measure the amount of drug excreted in urine in a time intervals 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose on Days 1 and 4. The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. fe% was calculated as fe% = (Ae 12 hours/Dose) multiply by 100. The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Renal Clearance (CLr) of Gepotidacin
Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. CLr was calculated as CLr = Ae 12 hours/AUC(0-tau). The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Urine Pre-dose Concentration (Ctau) of Gepotidacin
Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Measured: Days 1 to 5: Pre-dose
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious AEs (SAEs)
An AEs is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; and other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of gepotidacin.
Measured: Up to Day 31
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Vital signs including SBP and DBP were measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Pulse Rate
Vital sign including pulse rate was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Body Temperature
Vital sign including body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and Corrected QT Interval Using Fridericia's Formula (QTcF)
A 12-lead ECG was measured in semi-supine position using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.
Measured: Baseline; Day 1: 2 hours; Day 4: pre-dose and 2 hours
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Counts
Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet counts. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin
Blood samples were collected to analyze the hematology parameter: Erythrocyte Mean Corpuscular Hemoglobin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume
Blood samples were collected to analyze the hematology parameter: Erythrocyte Mean Corpuscular Volume. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Red Blood Cell Count
Blood samples were collected to analyze the hematology parameter: Red blood cell count. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Creatinine and Bilirubin
Blood samples were collected to analyze the chemistry parameters: Creatinine and Bilirubin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (ALP)
Blood samples were collected to analyze the chemistry parameters: ALT, AST and ALP. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea
Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Glucose and Nitrites
Urine samples were collected at indicated time points to analyze parameters including glucose and nitrites by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative and positive in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Ketones
Urine samples were collected at indicated time points to analyze parameter including ketones by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, 5 indicates 5 milligrams per deciliter (mg/dL) and 20 indicates 20 mg/dL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase
Urine samples were collected at indicated time points to analyze parameter including leukocyte esterase by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Trace indicates 15 Leukocytes per microliter (Leuko/mcL), Small indicates 70 Leuko/mcL, Moderate indicates 125 Leuko/mcL and Large indicates 500 Leuko/mcL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Occult Blood
Urine samples were collected at indicated time points to analyze parameter including occult blood by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Small indicates 25 Erythrocytes per microliter (Ery/mcL), Moderate indicates 50 Ery/mcL and Large indicates 250 Ery/mcL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Protein
Urine samples were collected at indicated time points to analyze parameter including protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative indicates <10 mg/dL, 1+ indicates 30 mg/dL and 2+ indicates 100 mg/dL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.
Measured: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Abnormal Physical Examination Findings
Physical examinations included assessments of the respiratory, cardiovascular, abdominal, gastrointestinal, neurological and urogenital systems. This analysis was planned but data was not collected and captured in the database.
Measured: Up to Day 31
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2018
- Study start23 Jul 2018
- Primary completion7 Jan 2019
- Study completion7 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Subjects will receive 1500 mg gepotidacin tablets BID via oral route for 5 days.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biomedical Advanced Research and Development Authority
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03568942
- Sponsor's protocol ID
- 206899
- Status last verified
- Jun 2020
- First submitted
- 11 Jun 2018
- Last updated
- 29 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Overcash JS, Tiffany CA, Scangarella-Oman NE, Perry CR, Tao Y, Hossain M, Barth A, Dumont EF. Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants with Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis). Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00199-20. doi: 10.1128/AAC.00199-20. Print 2020 Jun 23.
PubMed 32284384Nuzzo A, Van Horn S, Traini C, Perry CR, Dumont EF, Scangarella-Oman NE, Gardiner DF, Brown JR. Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944). BMC Microbiol. 2021 Jun 15;21(1):181. doi: 10.1186/s12866-021-02245-8.
PubMed 34130619
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa Single-Center, Open-Label Study Evaluating the Pharmacokinetics of Repeat Oral Doses of Gepotidacin (GSK2140944) in Adult Female Participants With Uncomplicated Urinary Tract Infection (Acute Cystitis)
- ClinicalTrials.gov ID
- NCT03568942
- Acronym / sponsor ID
- 206899
- Conditions
- Infections, Bacterial
- Keywords
- gepotidacin, GSK2140944, acute cystitis, pharmacokinetics, urinary tract infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Biomedical Advanced Research and Development Authority
- Study start
- 23 Jul 2018 (actual)
- Primary completion
- 7 Jan 2019 (actual)
- Study completion
- 7 Jan 2019 (actual)
- First posted
- 26 Jun 2018 (actual)
- Results
- Posted 7 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor that is being developed for the treatment of uncomplicated urinary tract infections (UTIs; acute cystitis). This Phase IIa study will evaluate plasma and urine pharmacokinetics of gepotidacin in female subjects with acute cystitis. Eligible female subjects will receive twice daily (BID) dose of gepotidacin 1500 milligram (mg) for 5 days via oral route. Pre-treatment and post-treatment samples for pharmacokinetic (PK) assessments will be collected throughout the study. The total duration of the study is approximately 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Subjects will receive 1500 mg gepotidacin tablets BID via oral route for 5 days.
| Arm | Type | Receives |
|---|---|---|
| Female subjects with acute cystitis | Experimental | Drug: GepotidacinAdult female subjects with suspected acute cystitis based on clinical presentation and pyuria (>=10 WBC/mm^3 or presence of leukocyte esterase) and/or nitrite will be included. Subjects will be administered 1500 mg gepotidacin BID for 5 days via the oral route. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject must be >=18 to <=65 years of age inclusive, at the time of signing the informed consent.
- The subject has 2 or more of the following clinical signs and symptoms of acute cystitis with onset <=72 hours of the screening assessment: dysuria, frequency, urgency, or lower abdominal pain.
- The subject has pyuria (>=10 white blood cells per cubic millimeters [WBC/mm^3] or the presence of leukocyte esterase) and/or nitrite from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
- The subject is female. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance from the Baseline Visit through completion of the Test of Cure (TOC) Visit.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Key exclusion criteria (29 listed)
- The subject resides in a nursing home or dependent care-type facility.
- The subject has a body mass index >=40.0 kilogram per square meter (kg/m^2) or a body mass index >=35.0 kg/m^2 with obesity-related health conditions such as high blood pressure or uncontrolled diabetes.
- The subject has a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation.
- The subject is immunocompromised or has altered immune defenses that may predispose the subject to a higher risk of treatment failure and/or complications (e.g., renal transplant recipients, subjects with clinically significant persistent granulocytopenia [absolute neutrophil count <1000/microliter (µL)], and subjects receiving immunosuppressive therapy, including corticosteroid therapy [>40 mg/day prednisolone or equivalent for >1 week or >=20 milligrams per day (mg/day) prednisolone or equivalent for >6 weeks; or prednisolone or equivalent >=10 mg/day for >6 weeks]). Subjects with a known cluster of differentiation 4 (CD4) count of <200 cells/mm^3 should not be enrolled.
- The subject has uncontrolled diabetes, defined as a non-fasting glucose value >300 milligrams per deciliter (mg/dL) or based on investigator judgment.
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 |
|---|---|---|
| GepotidacinGepotidacin tablets will be available at a dose strength of 750 mg. Tablets will be administered BID with water after consumption of food. | Drug | Female subjects with acute cystitis |
Primary outcome
Area Under the Plasma Concentration-time Curve (AUC) From Zero (Pre-dose) Over the Dosing Interval (AUC[0-tau]) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population consisted of all participants who received gepotidacin 1500 mg BID through the completion of all PK collections for whom valid and evaluable plasma PK parameters were derived for gepotidacin.
Maximum Plasma Concentration (Cmax) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Time of Occurrence of Cmax (Tmax) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
Apparent Steady State Clearance (CLss/F) of Gepotidacin
Time frame: Day 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. CLss/F was calculated as Dose divided by AUC(0-tau).
Accumulation Ratio (Ro) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Accumulation ratio (Ro) was calculated as ratio of AUC(0-tau) at Day 4 to AUC(0-tau) at Day 1.
Plasma Pre-dose Concentration (Ctau) of Gepotidacin
Time frame: Days 1 to 5: Pre-dose
Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.
26 secondary outcomes
Amount of Drug Excreted Over 12 Hours (Ae12hours) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Renal Clearance (CLr) of Gepotidacin
Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Urine Pre-dose Concentration (Ctau) of Gepotidacin
Time frame: Days 1 to 5: Pre-dose
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious AEs (SAEs)
Time frame: Up to Day 31
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Pulse Rate
Time frame: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Body Temperature
Time frame: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and Corrected QT Interval Using Fridericia's Formula (QTcF)
Time frame: Baseline; Day 1: 2 hours; Day 4: pre-dose and 2 hours
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Counts
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Hemoglobin
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Hematocrit
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Hematology Parameter: Red Blood Cell Count
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Creatinine and Bilirubin
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (ALP)
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Change From Baseline in Clinical Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Glucose and Nitrites
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Ketones
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Occult Blood
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Urinalysis Dipstick Results: Protein
Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Number of Participants With Abnormal Physical Examination Findings
Time frame: Up to Day 31
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32284384Overcash JS, Tiffany CA, Scangarella-Oman NE, Perry CR, Tao Y, Hossain M, Barth A, Dumont EF. Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants with Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis). Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00199-20. doi: 10.1128/AAC.00199-20. Print 2020 Jun 23.
- Derived from this study: PubMed 34130619Nuzzo A, Van Horn S, Traini C, Perry CR, Dumont EF, Scangarella-Oman NE, Gardiner DF, Brown JR. Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944). BMC Microbiol. 2021 Jun 15;21(1):181. doi: 10.1186/s12866-021-02245-8.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request 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 (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gepotidacin 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 5 inclusion and 29 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 29 Jun 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under the Plasma Concentration-time Curve (AUC) From Zero (Pre-dose) Over the Dosing Interval (AUC[0-tau]) of Gepotidacin (time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose). 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?
On the ClinicalTrials.gov record for NCT03568942, which also lists 2 linked publications.
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 29 Jun 2020.