Phase 3
N=1,531
A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (UTI)
Urinary Tract Infections
Bottom Line
View on ClinicalTrials.gov: NCT04020341 ↗Enrolled (actual)
1,531
Serious AEs
0.3%
Results posted
Jun 2023
Primary outcome: Primary: Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S (IA Set) — 162; 135; 158; 152 Participants — p=0.1445
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Gepotidacin (Drug); Placebo matching nitrofurantoin (Drug); Nitrofurantoin (Drug); Placebo matching gepotidacin (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- Female
- Sponsor
- GlaxoSmithKline
- Primary completion
- Nov 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S (IA Set) |
162; 135; 158; 152 | 0.1445 |
| PRIMARY Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Test-of-Cure (TOC) Visit - Micro-ITT NTF-S Population |
174; 140; 162; 158 | — |
| SECONDARY Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population |
224; 196; 82; 75; 9; 16 | — |
| SECONDARY Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population |
224; 196; 112; 102 | — |
| SECONDARY Number of Participants With Microbiological Outcome (MO) at the TOC Visit - Micro-ITT NTF-S Population |
244; 199; 15; 21; 36; 52 | — |
| SECONDARY Number of Participants With Microbiological Response at the TOC Visit - Micro-ITT NTF-S Population |
244; 199; 92; 99 | — |
| SECONDARY Number of Participants With Therapeutic Response (TR) (Combined Per Participant Clinical and Microbiological Response) at the Follow up (FU) Visit-Micro-ITT NTF-S Population |
117; 94; 219; 204 | — |
| SECONDARY Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Micro-ITT NTF-S Population |
184; 162; 61; 44; 28; 27 | — |
| SECONDARY Number of Participants With Clinical Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population |
184; 162; 152; 136 | — |
| SECONDARY Number of Participants With Microbiological Outcome (MO) at the Follow up (FU) Visit - Micro-ITT NTF-S Population |
174; 136; 32; 38; 36; 35 | — |
| SECONDARY Number of Participants With Microbiological Response at the Follow up (FU) Visit - Micro-ITT NTF-S Population |
174; 136; 162; 162 | — |
| SECONDARY Number of Participants With Clinical Outcome at the TOC Visit - Intent-to-Treat (ITT) Population |
497; 484; 194; 206; 26; 37 | — |
| SECONDARY Number of Participants With Clinical Response at the TOC Visit - Intent-to-Treat (ITT) Population |
497; 484; 270; 280 | — |
| SECONDARY Number of Participants With Clinical Outcome at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population |
421; 404; 130; 127; 75; 71 | — |
| SECONDARY Number of Participants With Clinical Response at the Follow up (FU) Visit - Intent-to-Treat (ITT) Population |
421; 404; 346; 360 | — |
| SECONDARY Plasma Concentration of Gepotidacin |
8.52; 2.96; 3.48; 4.20; 1.22; 1.10 | — |
| SECONDARY Urine Concentration of Gepotidacin |
317; 857; 391; 781; 363; 326 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
266; 165 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) |
2; 3 | — |
| SECONDARY Change From Baseline in Hematology Parameters - Neutrophil Count, Lymphocyte Count, Monocyte Count, Eosinophil Count, Basophil Count and Platelet Count at On Therapy and Test of Cure Visit |
0.053; 0.055; -0.001; 0.000; 0.002; 0.001 | — |
| SECONDARY Change From Baseline in Hematology Parameter-hemoglobin Level at On Therapy and Test of Cure Visit |
132.2; 131.7; -0.1; -0.4; -0.9; -1.6 | — |
| SECONDARY Change From Baseline in Hematology Parameter- Hematocrit Level at On Therapy and Test of Cure Visit |
0.4302; 0.4282; 0.0003; -0.0007; -0.0023; -0.0055 | — |
| SECONDARY Change From Baseline in Hematology Parameter- Erythrocytes Count at On Therapy and Test of Cure Visit |
4.538; 4.515; -0.005; -0.011; -0.033; -0.048 | — |
| SECONDARY Change From Baseline in Hematology Parameter - Mean Corpuscular Hemoglobin (MCH) at On Therapy and Test of Cure Visit |
29.20; 29.24; 0.02; -0.03; 0.02; -0.05 | — |
| SECONDARY Change From Baseline in Hematology Parameter - Mean Corpuscular Volume (MCV) at On Therapy and Test of Cure Visit |
95.02; 95.03; 0.17; 0.07; 0.17; -0.019 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters - Serum Urea Nitrogen, Glucose, Calcium, Chloride, Sodium, Magnesium, Phosphate, and Potassium Levels at On Therapy and Test of Cure Visit |
2.357; 2.374; -0.009; -0.012; -0.016; -0.016 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters - Total Bilirubin, Direct Bilirubin and Creatinine Levels at On Therapy and Test of Cure Visit |
4.71; 4.78; -0.26; -0.16; -0.24; -0.08 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters - Albumin and Protein Levels at On Therapy and Test of Cure Visit |
45.2; 45.4; 0.0; -0.3; -0.5; -0.5 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters - Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels at On Therapy and Test of Cure Visit |
79.0; 78.4; -0.5; 0.1; -1.5; 0.0 | — |
| SECONDARY Number of Participants With Urinalysis Dipstick Results at Baseline, On Therapy and Test of Cure Visit |
703; 717; 15; 5; 4; 3 | — |
| SECONDARY Absolute Mean Values of Urine Specific Gravity at Baseline, On Therapy and Test of Cure Visit |
1.0168; 1.0166; 1.0175; 1.0166; 1.0179; 1.0179 | — |
| SECONDARY Absolute Mean Values of Urine Potential of Hydrogen (pH) at Baseline, On Therapy and Test of Cure Visit |
5.6; 5.7; 5.6; 5.6; 5.6; 5.6 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at On-Therapy and Test of Cure Visit |
123.1; 123.4; -0.8; -1.4; -0.9; -1.2 | — |
| SECONDARY Change From Baseline in Pulse Rate at On Therapy and Test of Cure Visit |
73.5; 73.3; 1.4; 1.7; 1.2; 1.0 | — |
| SECONDARY Change From Baseline in Body Temperature at On Therapy and Test of Cure Visit |
36.62; 36.62; -0.04; -0.04; -0.04; -0.07 | — |
Summary
The study will be conducted to evaluate the therapeutic response (combined per participant microbiological and clinical response) of oral gepotidacin compared to oral nitrofurantoin for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female participants.
Eligibility Criteria
Inclusion Criteria
- Participants having >=12 years of age at the time of signing the informed consent/assent and have a body weight >=40 kilograms (kg).
- Participants having 2 or more of the following clinical signs and symptoms of acute cystitis with onset ]15 white blood cells [WBC]/high power field [HPF] or the presence of 3 plus [+]/large leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
- The participant is female.
- Participant is capable of giving signed informed consent/assent.
Exclusion Criteria
- Participant resides in a nursing home or dependent care type-facility.
- Participant has a body mass index >=40.0 kilogram per square meter (kg/m^2) or a body mass index >=35.0 kg/m^2 and is experiencing obesity-related health conditions such as uncontrolled high blood pressure or uncontrolled diabetes.
- Participant has a history of sensitivity to the study treatments, 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.
- Participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.
- Participant has any of the following:
- Poorly controlled asthma or chronic obstructive pulmonary disease; acute severe pain; active peptic ulcer disease; Parkinson disease; myasthenia gravis; Or
- Known acute porphyria.
- Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment.
- Participant has a known glucose-6-phosphate dehydrogenase deficiency.
- Participant has a serious underlying disease that could be imminently life-threatening, or the participant is unlikely to survive for the duration of the study period.
- Participant 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 Enterobacterales (other than Escherichia coli) as the contributing pathogen.
- Participant has symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis, that may interfere with the clinical efficacy assessments or preclude complete resolution of acute cystitis symptoms.
- Participant has an anatomical or physiological anomaly that predisposes the participant to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction or stricture of the urinary tract, primary renal disease (for example [e.g.], polycystic renal disease), or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesico-ureteral reflux, detrusor insufficiency).
- Participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
- Participant who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptom onset >=96 hours before study entry, or a temperature >=101.4 Degrees Fahrenheit (F) (>=38 Degrees Celsius [C]), flank pain, chills, or any other manifestations suggestive of upper UTI.
- Participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance =12 to 450 millisecond (msec) or a QTc >480 msec for participants with bundle-branch block.
- Participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.
- Participant has a known alanine aminotransferase (ALT) value >2 times upper limit of normal (ULN).
- Participant 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 percent [%]).
- Participant
Data sourced from ClinicalTrials.gov (NCT04020341). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.