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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04187144
• Collaborator: (none)
• Enrollment: 2,500
• Locations: 131
• Arms: 2
• Anticipated Duration (Months): 46.7
• Patients Per Site: 19.1
• 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: Apr 23, 2020
• 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 BID; approximately every 12 hours for 5 days.	Drug: Gepotidacin; Gepotidacin will be available as tablets at a unit dose strength of 750mg. Participants will administer two 750 mg tablets, BID. Each dose will be taken with water after consumption of food.; Drug: Placebo matching nitrofurantoin; Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Participants will administer 1 capsule BID. 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 100 mg capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Participants will administer one 100 mg capsule, BID. 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. Participants will administer two tablets, BID. 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. Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Up to Day 31]

7. 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)]

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

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

10. 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)]

11. 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)]

12. 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)]

13. 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)]

14. 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)]

15. 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)]

16. 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)]

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

18. 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)]

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

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

21. Change from Baseline in Electrocardiograms (ECG) parameters: QT interval corrected for heart rate according to Bazett's formula (QTcB) and QT interval corrected for heart rate according to Fridericia's formula (QTcF) (milliseconds [msec]) [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:

• The participant is >=12 years of age at the time of signing the informed consent/assent and has a body weight >=40 kilogram (kg).

• The participant has 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.

• The participant has nitrite or pyuria (greater than [>]15 white blood cell [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.

• The participant is capable of giving signed informed consent/assent.

Exclusion Criteria:

• The participant resides in a nursing home or dependent care type-facility.

• The participant has a body mass index >=40.0 kilogram per meter square (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.

• The participant 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 participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.

• The 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 intervention .

• The participant has a known glucose-6 phosphate dehydrogenase deficiency.

• The 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.

• The 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.

• The 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.

• The 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).

• The participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.

• The 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 degree Fahrenheit (>=38 Degrees Celsius [C]), flank pain, chills, or any other manifestations suggestive of upper UTI.

• The participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance <60 milliliters per minute (mL/min) or clinically significant elevated serum creatinine as determined by the investigator).

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

• The participant has congenital long QT syndrome or known prolongation of the QTc interval.

• The participant has uncompensated heart failure.

• The participant has severe left ventricular hypertrophy.

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

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

• The 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 ECG reading.

• The participant has a QTc >450 msec or a QTc >480 msec for participants with bundle-branch block.

• The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.

• The participant has a known ALT value >2 times upper limit of normal (ULN).

• The 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 [%]).

• The participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice.

• The participant has a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.

• The 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	Homewood	Alabama	United States	35209
3	GSK Investigational Site	Huntsville	Alabama	United States	35801
4	GSK Investigational Site	Gilbert	Arizona	United States	85296
5	GSK Investigational Site	Phoenix	Arizona	United States	85015-1104
6	GSK Investigational Site	Phoenix	Arizona	United States	85015-1104
7	GSK Investigational Site	La Mesa	California	United States	91942
8	GSK Investigational Site	Northridge	California	United States	91324
9	GSK Investigational Site	Sacramento	California	United States	95821
10	GSK Investigational Site	Valencia	California	United States	91355-5319
11	GSK Investigational Site	Washington	District of Columbia	United States	20011
12	GSK Investigational Site	Apollo Beach	Florida	United States	33572
13	GSK Investigational Site	Boynton Beach	Florida	United States	33435
14	GSK Investigational Site	Clearwater	Florida	United States	33761
15	GSK Investigational Site	Coconut Creek	Florida	United States	33063
16	GSK Investigational Site	Hialeah	Florida	United States	33013
17	GSK Investigational Site	Lake Worth	Florida	United States	33461
18	GSK Investigational Site	Leesburg	Florida	United States	34748
19	GSK Investigational Site	Miami	Florida	United States	33126
20	GSK Investigational Site	Miami	Florida	United States	33135
21	GSK Investigational Site	Miami	Florida	United States	33155
22	GSK Investigational Site	Orlando	Florida	United States	32810
23	GSK Investigational Site	Ormond Beach	Florida	United States	32174
24	GSK Investigational Site	Palm Springs	Florida	United States	33406
25	GSK Investigational Site	Pembroke Pines	Florida	United States	33026-4383
26	GSK Investigational Site	Sweetwater	Florida	United States	33172
27	GSK Investigational Site	Tampa	Florida	United States	33614
28	GSK Investigational Site	West Palm Beach	Florida	United States	33409
29	GSK Investigational Site	West Palm Beach	Florida	United States	33409
30	GSK Investigational Site	Blackfoot	Idaho	United States	83221
31	GSK Investigational Site	Boise	Idaho	United States	83704
32	GSK Investigational Site	Meridian	Idaho	United States	83642
33	GSK Investigational Site	El Dorado	Kansas	United States	67042
34	GSK Investigational Site	Wichita	Kansas	United States	67205
35	GSK Investigational Site	Hanover	Maryland	United States	21076
36	GSK Investigational Site	Fall River	Massachusetts	United States	02723
37	GSK Investigational Site	Butte	Montana	United States	59701
38	GSK Investigational Site	Hastings	Nebraska	United States	68901
39	GSK Investigational Site	Lincoln	Nebraska	United States	68510
40	GSK Investigational Site	East Orange	New Jersey	United States	07018-1502
41	GSK Investigational Site	Lawrenceville	New Jersey	United States	08648
42	GSK Investigational Site	Mount Laurel	New Jersey	United States	08054
43	GSK Investigational Site	Albuquerque	New Mexico	United States	87102
44	GSK Investigational Site	Brooklyn	New York	United States	11229
45	GSK Investigational Site	New York	New York	United States	10016-7313
46	GSK Investigational Site	New York	New York	United States	10016
47	GSK Investigational Site	New York	New York	United States	13760-3646
48	GSK Investigational Site	Cary	North Carolina	United States	27518
49	GSK Investigational Site	Mount Airy	North Carolina	United States	27030
50	GSK Investigational Site	Raleigh	North Carolina	United States	27612
51	GSK Investigational Site	Texas	North Carolina	United States	78229
52	GSK Investigational Site	Wilmington	North Carolina	United States	28412
53	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
54	GSK Investigational Site	Fargo	North Dakota	United States	58104
55	GSK Investigational Site	Cincinnati	Ohio	United States	45215
56	GSK Investigational Site	Columbus	Ohio	United States	43213
57	GSK Investigational Site	Columbus	Ohio	United States	43214
58	GSK Investigational Site	Columbus	Ohio	United States	43231
59	GSK Investigational Site	Dayton	Ohio	United States	45424
60	GSK Investigational Site	Eugene	Oregon	United States	97404
61	GSK Investigational Site	Bala-Cynwyd	Pennsylvania	United States	19004
62	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19107
63	GSK Investigational Site	Anderson	South Carolina	United States	29621
64	GSK Investigational Site	Greenville	South Carolina	United States	29615
65	GSK Investigational Site	Greenville	South Carolina	United States	29615
66	GSK Investigational Site	Lancaster	South Carolina	United States	29720
67	GSK Investigational Site	Union	South Carolina	United States	29379
68	GSK Investigational Site	Bristol	Tennessee	United States	37620
69	GSK Investigational Site	Milan	Tennessee	United States	38358
70	GSK Investigational Site	New Tazewell	Tennessee	United States	37824-1409
71	GSK Investigational Site	Austin	Texas	United States	78735
72	GSK Investigational Site	Austin	Texas	United States	78744 -1645
73	GSK Investigational Site	Austin	Texas	United States	78758
74	GSK Investigational Site	Houston	Texas	United States	77087
75	GSK Investigational Site	Katy	Texas	United States	77450
76	GSK Investigational Site	Mesquite	Texas	United States	75149
77	GSK Investigational Site	Missouri City	Texas	United States	77459
78	GSK Investigational Site	North Richland Hills	Texas	United States	76180
79	GSK Investigational Site	Plano	Texas	United States	75024
80	GSK Investigational Site	San Antonio	Texas	United States	78209
81	GSK Investigational Site	San Antonio	Texas	United States	78251
82	GSK Investigational Site	Bountiful	Utah	United States	84010
83	GSK Investigational Site	Saint George	Utah	United States	84790
84	GSK Investigational Site	Saint George	Utah	United States	84790
85	GSK Investigational Site	Salt Lake City	Utah	United States	84107
86	GSK Investigational Site	Midlothian	Virginia	United States	23114
87	GSK Investigational Site	Richmond	Virginia	United States	23225
88	GSK Investigational Site	Richmond	Virginia	United States	23235
89	GSK Investigational Site	Darlinghurst, Sydney	New South Wales	Australia	2010
90	GSK Investigational Site	Maroubra	New South Wales	Australia	2035
91	GSK Investigational Site	Sydney	New South Wales	Australia	2010
92	GSK Investigational Site	Tarragindi	Queensland	Australia	4121
93	GSK Investigational Site	Gabrovo		Bulgaria	5300
94	GSK Investigational Site	Haskovo		Bulgaria	6300
95	GSK Investigational Site	Kyustendil		Bulgaria	2500
96	GSK Investigational Site	Montana		Bulgaria	3400
97	GSK Investigational Site	Pleven		Bulgaria	5800
98	GSK Investigational Site	Ruse		Bulgaria	7000
99	GSK Investigational Site	Shumen		Bulgaria	9700
100	GSK Investigational Site	Sofia		Bulgaria	1606
101	GSK Investigational Site	Stara Zagora		Bulgaria	6000
102	GSK Investigational Site	Targovisthe		Bulgaria	7700
103	GSK Investigational Site	Hyderabad		India	500004
104	GSK Investigational Site	Jagatpura		India	302025
105	GSK Investigational Site	Nagpur		India	440015
106	GSK Investigational Site	Nashik		India	422101
107	GSK Investigational Site	New Delhi		India	110062
108	GSK Investigational Site	Pune		India	411016
109	GSK Investigational Site	Rajkot		India	360005
110	GSK Investigational Site	Ansan-si		Korea, Republic of	15355
111	GSK Investigational Site	Bucheon-si		Korea, Republic of	14647
112	GSK Investigational Site	Busan		Korea, Republic of	49201
113	GSK Investigational Site	Goyang-si, Gyeonggi-do		Korea, Republic of	10326
114	GSK Investigational Site	Hwasun-gun, Jeollanam-do		Korea, Republic of	58128
115	GSK Investigational Site	Incheon		Korea, Republic of	21565
116	GSK Investigational Site	Sejong-si		Korea, Republic of	30099
117	GSK Investigational Site	Seoul		Korea, Republic of	06973
118	GSK Investigational Site	Seoul		Korea, Republic of	2447
119	GSK Investigational Site	Suwon		Korea, Republic of	16247
120	GSK Investigational Site	Uijeongbu-si		Korea, Republic of	11765
121	GSK Investigational Site	Bialystok		Poland	15224
122	GSK Investigational Site	Katowice		Poland	40-156
123	GSK Investigational Site	Katowice		Poland	40-748
124	GSK Investigational Site	Katowice		Poland	40611
125	GSK Investigational Site	Krakow		Poland	30721
126	GSK Investigational Site	Lublin		Poland	20064
127	GSK Investigational Site	Ostrowiec Swietokrzyski		Poland	27-400
128	GSK Investigational Site	Piaseczno		Poland	05500
129	GSK Investigational Site	Swidnik		Poland	21-040
130	GSK Investigational Site	Torun		Poland	87-100
131	GSK Investigational Site	Warszawa		Poland	02798

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: NCT04187144
• Other Study ID Numbers: 212390
• First Posted: Dec 5, 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