A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (UTI)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04020341
• Collaborator: (none)
• Enrollment: 2,500
• Locations: 129
• Arms: 2
• Anticipated Duration (Months): 52.9
• Patients Per Site: 19.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Tract Infections	Drug: Gepotidacin; Drug: Placebo matching nitrofurantoin; Drug: Nitrofurantoin; Drug: Placebo matching gepotidacin	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 2500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Multicenter, Parallel-Group, Double-Blind, Double-Dummy Study in Adolescent and Adult Female Participants Comparing the Efficacy and Safety of Gepotidacin to Nitrofurantoin in the Treatment of Uncomplicated Urinary Tract Infection (Acute Cystitis)
• Actual Study Start Date: Oct 17, 2019
• Anticipated Primary Completion Date: Mar 13, 2024
• Anticipated Study Completion Date: Mar 13, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gepotidacin Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo twice daily (BID); approximately every 12 hours for 5 days	Drug: Gepotidacin; Gepotidacin will be available as tablets containing 750 mg gepotidacin. Each dose should be taken with water after consumption of food.; Drug: Placebo matching nitrofurantoin; Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Each dose should be taken with water after consumption of food.
Active Comparator: Nitrofurantoin Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.	Drug: Nitrofurantoin; Nitrofurantoin will be available as over-encapsulated capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Each dose should be taken with water after consumption of food.; Drug: Placebo matching gepotidacin; Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Each dose should be taken with water after consumption of food.

Outcome Measures

Primary Outcome Measures

1. Number of participants with therapeutic response (combined per participant clinical and microbiological response) at the Test-of-Cure (TOC) visit [Days 10 to 13]

   A therapeutic success refers to participants who have been deemed both a "microbiological success" (reduction of all qualifying bacterial uropathogens [greater than or equal to {>=}10^5 colony-forming units per milliliter {CFU/mL}] recovered at Baseline to less than (<)10^3 CFU/mL as observed on quantitative urine culture without the participant receiving other systemic antimicrobials before the TOC Visit) and a "clinical success" (resolution of signs and symptoms of acute cystitis present at Baseline [and no new signs and symptoms] without the participant receiving other systemic antimicrobials before the TOC Visit). All other combinations (other than clinical success + microbiological success) are deemed failures for therapeutic response.

Secondary Outcome Measures

1. Number of participants with clinical outcome and response at the TOC visit [Days 10 to 13]

   Clinical success (response) is defined as clinical resolution. Clinical resolution (outcome) is defined as resolution of signs and symptoms of acute cystitis present at Baseline [and no new signs and symptoms] without the participant receiving other systemic antimicrobials before the TOC visit.

2. Number of participants with clinical outcome and response at the follow-up visit [Days 25 to 31]

   Clinical success (response) is defined as sustained clinical resolution. Sustained clinical resolution (outcome) is defined as resolution of signs and symptoms of acute cystitis demonstrated at the TOC Visit persist at the Follow-up Visit (and no new signs and symptoms), without the participant receiving other systemic antimicrobials before the Follow-up visit.

3. Number of participants with per participant microbiological outcome and response at the TOC visit [Days 10 to 13]

   Participant-level microbiological success (response) is defined as microbiological eradication. Microbiological eradication (outcome) is defined as reduction of all qualifying bacterial uropathogens [>=10^5 CFU/mL] recovered at Baseline to <10^3 CFU/mL as observed on quantitative urine culture without the participant receiving other systemic antimicrobials before the TOC Visit.

4. Number of participants with per participant microbiological outcome and response at the follow-up visit [Days 25 to 31]

   Participant-level microbiological success (response) is defined as sustained microbiological eradication. Sustained microbiological eradication (outcome) is defined as reduction of all qualifying bacterial uropathogens [>=10^5 CFU/mL] recovered at Baseline to <10^3 CFU/mL as observed on quantitative urine culture, following microbiological eradication at the TOC Visit, without the participant receiving other systemic antimicrobials before the TOC Visit.

5. Number of participants with therapeutic response (combined per participant clinical and microbiological response) at the follow-up visit [Days 25 to 31]

   A therapeutic success refers to participants who have been deemed both a "microbiological success" (sustained microbiological eradication) and a "clinical success" (sustained symptom resolution). All other combinations (other than clinical success + microbiological success) will be deemed failures for therapeutic response.

6. Plasma concentration of gepotidacin [Up to Day 5]

7. Urine concentration of gepotidacin [Up to Day 5]

8. Number of participants with Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Up to Day 31]

9. Change from Baseline in hematology parameters: neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per Liter) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

10. Change from Baseline in hematology parameter: hemoglobin level [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

11. Change from Baseline in hematology parameter: hematocrit level [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

12. Change from Baseline in hematology parameter: Red blood cell (RBC) count [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

13. Change from Baseline in hematology parameter: Mean corpuscular hemoglobin (MCH) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

14. Change from Baseline in hematology parameter: Mean corpuscular volume (MCV) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

15. Change from Baseline in clinical chemistry parameters: Blood urea nitrogen (BUN), glucose non-fasting, calcium, chloride, sodium, magnesium, phosphorus and potassium levels (Millimoles per Liter) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

16. Change from Baseline in clinical chemistry parameters: Total bilirubin, direct bilirubin and creatinine levels (Micromoles per Liter) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

17. Change from Baseline in clinical chemistry parameters: Albumin and total protein levels (Gram per Liter) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

18. Change from Baseline in clinical chemistry parameters: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per Liter) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

19. Number of participants with abnormal urinalysis Dipstick results [Days 10 to 13]

20. Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (Millimeters of mercury [mmHg]) [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

21. Change from Baseline in pulse rate [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

22. Change from Baseline in body temperature [Baseline, On-Therapy (Days 2 to 4), and Test of cure (Days 10 to 13)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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 <96 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain.

• Participants having nitrite or pyuria (greater than [>]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:

1. Poorly controlled asthma or chronic obstructive pulmonary disease; acute severe pain; active peptic ulcer disease; Parkinson disease; myasthenia gravis; Or

2. Known acute porphyria.

3. 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 <60 milliliter per minute [mL/min] or clinically significant elevated serum creatinine as determined by the investigator).

• Participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).

• Participant has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.

• Participant has uncompensated heart failure.

• Participant has severe left ventricular hypertrophy.

• Participant has a family history of QT prolongation or sudden death.

• Participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady-arrhythmia within the last 12 months.

• Participant is taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes (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 participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor.

• For any participant >=12 to <18 years of age, the participant has an abnormal electrocardiogram (ECG) reading.

• Participant has a QTc >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 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).

• Participant has a previous history of cholestatic jaundice or hepatic dysfunction associated with nitrofurantoin.

• Participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35205
2	GSK Investigational Site	Phoenix	Arizona	United States	85051
3	GSK Investigational Site	Tucson	Arizona	United States	85712
4	GSK Investigational Site	Beverly Hills	California	United States	90211-2921
5	GSK Investigational Site	Chula Vista	California	United States	91911
6	GSK Investigational Site	La Mesa	California	United States	91942
7	GSK Investigational Site	Lomita	California	United States	90717
8	GSK Investigational Site	Long Beach	California	United States	90806
9	GSK Investigational Site	Northridge	California	United States	91324-3331
10	GSK Investigational Site	Northridge	California	United States	91324-3528
11	GSK Investigational Site	Palm Springs	California	United States	92264
12	GSK Investigational Site	San Diego	California	United States	92120
13	GSK Investigational Site	DeLand	Florida	United States	32720
14	GSK Investigational Site	Hialeah	Florida	United States	33016
15	GSK Investigational Site	Miami Springs	Florida	United States	33166
16	GSK Investigational Site	Miami	Florida	United States	33144
17	GSK Investigational Site	Orlando	Florida	United States	32806
18	GSK Investigational Site	Pompano Beach	Florida	United States	33060
19	GSK Investigational Site	Atlanta	Georgia	United States	30328
20	GSK Investigational Site	Columbus	Georgia	United States	31901-2561
21	GSK Investigational Site	Fayetteville	Georgia	United States	31204
22	GSK Investigational Site	Wichita	Kansas	United States	67226-3007
23	GSK Investigational Site	New Orleans	Louisiana	United States	70115
24	GSK Investigational Site	Shreveport	Louisiana	United States	71106
25	GSK Investigational Site	Watertown	Massachusetts	United States	02472
26	GSK Investigational Site	Dearborn Heights	Michigan	United States	48127-3163
27	GSK Investigational Site	Flint	Michigan	United States	48532
28	GSK Investigational Site	Norfolk	Nebraska	United States	68701-2669
29	GSK Investigational Site	East Brunswick	New Jersey	United States	08816-1407
30	GSK Investigational Site	East Brunswick	New Jersey	United States	08816-1407
31	GSK Investigational Site	Albuquerque	New Mexico	United States	87109
32	GSK Investigational Site	Endwell	New York	United States	13760
33	GSK Investigational Site	Fayetteville	North Carolina	United States	28304
34	GSK Investigational Site	Scottdale	Pennsylvania	United States	15683
35	GSK Investigational Site	Smithfield	Pennsylvania	United States	15478
36	GSK Investigational Site	Clarksville	Tennessee	United States	37043-1524
37	GSK Investigational Site	Clarksville	Tennessee	United States	37043-1524
38	GSK Investigational Site	Memphis	Tennessee	United States	38120
39	GSK Investigational Site	Arlington	Texas	United States	76014
40	GSK Investigational Site	Austin	Texas	United States	78705
41	GSK Investigational Site	Corpus Christi	Texas	United States	78414
42	GSK Investigational Site	Dallas	Texas	United States	75209
43	GSK Investigational Site	Forney	Texas	United States	75126
44	GSK Investigational Site	Houston	Texas	United States	77055
45	GSK Investigational Site	Houston	Texas	United States	77065-5597
46	GSK Investigational Site	Morgantown	West Virginia	United States	26505-0423
47	GSK Investigational Site	Blagoevgrad		Bulgaria	2700
48	GSK Investigational Site	Blagoevgrad		Bulgaria	2700
49	GSK Investigational Site	Dupnitsa		Bulgaria	2600
50	GSK Investigational Site	Pernik		Bulgaria	5800
51	GSK Investigational Site	Pleven		Bulgaria	5800
52	GSK Investigational Site	Pleven		Bulgaria	5800
53	GSK Investigational Site	Plovdiv		Bulgaria	4000
54	GSK Investigational Site	Sliven		Bulgaria	8800
55	GSK Investigational Site	Smolyan		Bulgaria	4700
56	GSK Investigational Site	Sofia		Bulgaria	1000
57	GSK Investigational Site	Sofia		Bulgaria	1408
58	GSK Investigational Site	Sofia		Bulgaria	1408
59	GSK Investigational Site	Sofia		Bulgaria	1431
60	GSK Investigational Site	Yambol		Bulgaria	8600
61	GSK Investigational Site	Bory		Czechia	305 99
62	GSK Investigational Site	Hradec Králové		Czechia	500 05
63	GSK Investigational Site	Kromeríž		Czechia	767 01
64	GSK Investigational Site	Novy Jicin		Czechia	741 01
65	GSK Investigational Site	Opava		Czechia	746 01
66	GSK Investigational Site	Praha		Czechia	120 00
67	GSK Investigational Site	Praha		Czechia	130 00
68	GSK Investigational Site	Uherské Hradište		Czechia	686 06
69	GSK Investigational Site	Vsetín		Czechia	755 01
70	GSK Investigational Site	Giessen	Hessen	Germany	35385
71	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45355
72	GSK Investigational Site	Muelheim an der Ruhr	Nordrhein-Westfalen	Germany	45468
73	GSK Investigational Site	Berlin		Germany	10439
74	GSK Investigational Site	Hamburg		Germany	20146
75	GSK Investigational Site	Heraklion		Greece	71110
76	GSK Investigational Site	Larisa		Greece	41110
77	GSK Investigational Site	Thessaloniki		Greece	546 42
78	GSK Investigational Site	Thessaloniki		Greece	54635
79	GSK Investigational Site	Thessaloniki		Greece	56403
80	GSK Investigational Site	Ballószög		Hungary	6035
81	GSK Investigational Site	Budapest		Hungary	1204
82	GSK Investigational Site	Csongrad		Hungary	6640
83	GSK Investigational Site	Nyíregyháza		Hungary	4400
84	GSK Investigational Site	Orosháza-Szentetornya		Hungary	5905
85	GSK Investigational Site	Ahmedabad		India	380016
86	GSK Investigational Site	Jaipur		India	302004
87	GSK Investigational Site	Mumbai		India	400053
88	GSK Investigational Site	Surat		India	395002
89	GSK Investigational Site	Varanasi		India	221010
90	GSK Investigational Site	Ciudad de Mexico	Campeche	Mexico	06100
91	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44160
92	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44280
93	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64000
94	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64460
95	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64460
96	GSK Investigational Site	San Juan del Río	Querétaro	Mexico	76800
97	GSK Investigational Site	Jalisco		Mexico	44130
98	GSK Investigational Site	Brasov		Romania	500152
99	GSK Investigational Site	Bucharest		Romania	021105
100	GSK Investigational Site	Bucharest		Romania	022328
101	GSK Investigational Site	Bucharest		Romania	050653
102	GSK Investigational Site	Bucharest		Romania	050653
103	GSK Investigational Site	Bucuresti		Romania	022328
104	GSK Investigational Site	Iasi		Romania	700116
105	GSK Investigational Site	Oradea		Romania	410469
106	GSK Investigational Site	Timisoara		Romania	300736
107	GSK Investigational Site	Bratislava		Slovakia	851 05
108	GSK Investigational Site	Kosice		Slovakia	040 01
109	GSK Investigational Site	Nitra		Slovakia	949 01
110	GSK Investigational Site	Poprad		Slovakia	058 01
111	GSK Investigational Site	Presov		Slovakia	081 81
112	GSK Investigational Site	Pruske		Slovakia	018 52
113	GSK Investigational Site	Sala		Slovakia	927 01
114	GSK Investigational Site	Trencin		Slovakia	911 01
115	GSK Investigational Site	Trencin		Slovakia	911 05
116	GSK Investigational Site	Alicante		Spain	03010
117	GSK Investigational Site	Cordoba		Spain	14004
118	GSK Investigational Site	Madrid		Spain	28023
119	GSK Investigational Site	Madrid		Spain	28041
120	GSK Investigational Site	Madrid		Spain	28044
121	GSK Investigational Site	Madrid		Spain	28050
122	GSK Investigational Site	Valencia		Spain	46026
123	GSK Investigational Site	Vic		Spain	08500
124	GSK Investigational Site	Eastleigh	Hampshire	United Kingdom	SO53 4ST
125	GSK Investigational Site	Hinckley	Leicestershire	United Kingdom	LE10 2SE
126	GSK Investigational Site	Crownhill, Plymouth		United Kingdom	PL5 3JB
127	GSK Investigational Site	Liskeard		United Kingdom	PL14 3XA
128	GSK Investigational Site	Peterborough		United Kingdom	PE8 6PL
129	GSK Investigational Site	Witney		United Kingdom	OX28 6JS

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04020341
• Other Study ID Numbers: 204989
• First Posted: Jul 16, 2019
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Acute cystitis; Efficacy; Gepotidacin; Nitrofurantoin; Urinary Tract Infection; Simple cystitis
• Additional relevant MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Nitrofurantoin

Study Results

No Results Posted as of Jun 28, 2022