GSK3882347 for Urinary Tract Infection (UTI)

Recruiting at 17 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Female

Travel: May Be Covered

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Systemic antimicrobials, Systemic antifungals

Disqualifiers: Obesity, Immunocompromised, Anatomical anomalies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 5 days

140 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken other systemic antimicrobials or systemic antifungals within 1 week (or 10 weeks for dalbavancin or oritavancin) before joining the study.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken other systemic antimicrobials or systemic antifungals within 1 week before the study, or 10 weeks for certain drugs like dalbavancin or oritavancin.

What data supports the idea that GSK3882347 for Urinary Tract Infection is an effective drug?

The available research shows that nitrofurantoin, which is another name for GSK3882347, has been used successfully for many years to treat urinary tract infections. It remains effective against common bacteria that cause these infections, like Escherichia coli. Recent studies suggest that short-term use of nitrofurantoin is as effective as other standard treatments, and it is recommended as a first-choice treatment for uncomplicated urinary tract infections in healthy women. However, it should be used cautiously in people with kidney problems and during the last three months of pregnancy. ^{1 2 3 4 5}

What data supports the effectiveness of the drug GSK3882347 for urinary tract infections?

Nitrofurantoin, a component of the treatment, has been used successfully for many years to treat urinary tract infections, especially in cases where bacteria are resistant to other antibiotics. It is effective against common bacteria that cause these infections, making it a reliable option for treatment. ^{1 2 3 4 5}

What safety data exists for GSK3882347 (Nitrofurantoin) in treating urinary tract infections?

Nitrofurantoin, also known as GSK3882347, has been used successfully for a long time to treat urinary tract infections and is generally considered safe. Studies have shown it to be effective in adults, children, and pregnant women, with no significant adverse effects on fetal development. However, rare adverse reactions, such as systemic inflammatory response syndrome, have been reported. Overall, nitrofurantoin is well-tolerated, but patients should be informed about potential side effects. ^{1 5 6 7 8}

What safety data exists for GSK3882347 (Nitrofurantoin) in humans?

Nitrofurantoin has been used safely for a long time to treat urinary tract infections in adults, children, and pregnant women, with no significant safety concerns reported. However, there are rare cases of serious side effects, such as a systemic inflammatory response, which should be monitored. ^{1 5 6 7 8}

Is the drug Nitrofurantoin a promising treatment for urinary tract infections?

Yes, Nitrofurantoin is a promising treatment for urinary tract infections. It has been used successfully for many years and remains effective against common bacteria that cause these infections. It is especially useful now because it works well against bacteria that are resistant to other antibiotics. ^{3 4 5 7 9}

How is the drug GSK3882347 different from other treatments for urinary tract infections?

GSK3882347, also known as nitrofurantoin, is unique because it remains effective against many bacteria that have become resistant to other antibiotics, making it a valuable option for treating urinary tract infections, especially those caused by multidrug-resistant bacteria. ^{3 4 5 7 9}

What is the purpose of this trial?

This trial tests a new medication, GSK3882347, to treat urinary tract infections in adult women. The study will see if the medication can effectively clear the infection and check for any side effects. Participants will take the medication for a short period, and researchers will compare it to an existing treatment to ensure accurate results.

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for adult women aged 18-70 with uncomplicated urinary tract infections (uUTI), not pregnant or breastfeeding, and using effective contraception. They must have symptoms like pain during urination, frequent urge to urinate, or lower abdominal pain. Women with immune issues, other diseases causing similar symptoms, urinary anomalies, severe kidney problems, recent antimicrobial treatment or high alcohol intake are excluded.

Inclusion Criteria

The participant has 2 or more of the following clinical signs and symptoms of uncomplicated urinary tract infections (uUTI) with onset less than (<) 96 hours of the screening assessment: dysuria, frequency, urgency, or lower abdominal pain

A female participant is eligible to participate who is not pregnant (as confirmed by a highly sensitive pregnancy test before the first dose of study intervention) or breastfeeding and one of the following conditions apply: Woman participant of non-childbearing potential (WONCBP) Or Woman participant of childbearing potential (WOCBP) using a contraceptive method that is highly effective, with a failure rate of < 1 percentage (%), during the study intervention period and up to 5 days post intervention

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol

Exclusion Criteria

You have a weakened immune system that may increase the risk of treatment failure or complications.

You have symptoms that may be caused by a different medical condition, such as chronic bladder issues or asymptomatic bacteriuria.

You have a physical condition that increases your risk of developing urinary tract infections, such as blockages or abnormalities in your urinary tract or a history of such conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive daily oral dosing of GSK3882347 or nitrofurantoin for 5 days

5 days

Inpatient for Cohort 1, Outpatient for Cohort 2

Test of Cure (ToC)

Microbiological response is evaluated at the test of cure visit

Day 10 to Day 13

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to Day 31

Treatment Details

Interventions

• GSK3882347
• Nitrofurantoin
• Placebo

Trial Overview The study tests GSK3882347's safety and effectiveness against uUTI compared to Nitrofurantoin and a placebo over 5 days. It includes two groups: one staying in the hospital for detailed daily checks (Cohort 1) and another treated as outpatients with less frequent checks (Cohort 2).

Participant Groups

Group I: GSK3882347 + Placebo Experimental Treatment 2 Interventions

Participants will be administered GSK3882347 plus placebo.

Group II: Nitrofurantoin+ Placebo Active Control 2 Interventions

Participants will be administered nitrofurantoin plus placebo.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

A retrospective analysis of 91 pregnancies treated with nitrofurantoin macrocrystals for urinary tract infections found no significant increase in adverse outcomes for the fetus compared to the general U.S. population.

The study concluded that nitrofurantoin macrocrystals do not appear to be toxic to the fetus, suggesting it is a safe option for treating urinary tract infections in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Foetal safety of nitrofurantoin macrocrystals therapy during pregnancy: a retrospective analysis. Hailey, FJ., Fort, H., Williams, JC., et al.[2017]

In a study of over 29,000 women, nitrofurantoin was found to be equally effective in treating urinary tract infections (UTIs) in those with moderate renal impairment compared to those without, showing no increased risk of treatment ineffectiveness.

However, women with more severe renal impairment (less than 50 ml/min) had a significantly higher risk of serious pulmonary adverse events leading to hospitalization when treated with nitrofurantoin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care. Geerts, AF., Eppenga, WL., Heerdink, R., et al.[2021]

Nitrofurantoin remains an effective treatment for uncomplicated urinary tract infections (UTIs), particularly against common pathogens like E. coli, despite its long history of use and potential side effects.

Recent studies indicate that short-term nitrofurantoin therapy is well-tolerated and effective, making it a recommended first-line treatment in current guidelines, although it is contraindicated in late pregnancy and for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections]. Stock, I.[2014]

In a study of 105 type 2 diabetic women aged 50-70, nitrofurantoin was found to be an effective treatment for recurrent urinary tract infections (UTIs), showing similar efficacy to cotrimoxazole over a 12-month observation period.

Both nitrofurantoin and cotrimoxazole resulted in comparable rates of clinical cure and bacteriological eradication, indicating that nitrofurantoin is a viable option for managing recurrent UTIs in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of nitrofurantoin in the treatment of chronic urinary tract infections in patients with type 2 diabetes mellitus]. Mozdzan, M., Ruxer, J., Siejka, A., et al.[2020]

Nitrofurantoin is a broad-spectrum antibiotic effective against both Gram-negative and Gram-positive bacteria, making it a valuable option for treating acute lower urinary tract infections, especially in the context of rising antibiotic resistance.

Recent data suggest that nitrofurantoin is particularly useful for managing urinary tract infections caused by multidrug-resistant pathogens, highlighting its importance as a treatment option when other oral antibiotics are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Old Antibiotics in the Era of Antibiotic Resistance. Highlighted Nitrofurantoin for the Treatment of Lower Urinary Tract Infections. Munoz-Davila, MJ.[2020]

In studies involving rats and rabbits, nitrofurantoin macrocrystals were administered at doses up to six times the human therapeutic dose, showing no adverse effects on maternal health, fetal development, or neonatal survival.

The results suggest that nitrofurantoin macrocrystals are a safe option for treating urinary tract infections in pregnant women, as they did not cause any reproductive or developmental toxicity in the animal models tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General reproduction, perinatal-postnatal, and teratology studies of nitrofurantoin macrocrystals in rats and rabbits. Prytherch, JP., Sutton, ML., Denine, EP.[2013]

In a study involving 65 hospitalized patients with acute urinary tract infections, treatment with a nitrofurantoin/sulphadiazine compound showed therapeutic effectiveness, highlighting its potential as a reliable antibacterial option.

The study emphasized the importance of monitoring for iatrogenic infections, as these patients were already severely ill, indicating a need for careful management to minimize additional risks during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of acute urinary tract infection with a nitrofurantoin-sulphadiazine compound preparation (author's transl)]. Griendl, W.[2013]

Nitrofurantoin, while generally safe for treating lower urinary tract infections, can cause rare but serious adverse effects, such as systemic inflammatory response syndrome, as demonstrated in a case involving a 66-year-old woman.

The patient's symptoms resolved completely after discontinuing nitrofurantoin, highlighting the importance of monitoring for adverse reactions and educating patients about potential side effects of this antibiotic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Inflammatory Response Syndrome from Nitrofurantoin: A Case Report. O'Connor, RA., Patel, V., Lang, V., et al.[2022]

The study identified that a nitrofurantoin suspension with glycerin (0.2%) and sodium citrate (0.3%) significantly improved physical stability, making it a promising formulation for treating urinary tract infections.

The optimal formulation, which included Veegum (1%), sodium carboxyl methyl cellulose (1%), glycerin, sodium citrate, and sorbitol (20%), exhibited pseudoplastic behavior, indicating good flow properties and ease of use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of flocculating agents and structural vehicles on the physical stability and rheological behavior of nitrofurantoin suspension. Moghimipour, E., Salimi, A., Rezaee, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Foetal safety of nitrofurantoin macrocrystals therapy during pregnancy: a retrospective analysis. [2017]

2. Germany pubmed.ncbi.nlm.nih.gov

Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

[Nitrofurantoin--clinical relevance in uncomplicated urinary tract infections]. [2014]

4. Poland pubmed.ncbi.nlm.nih.gov

[Efficacy of nitrofurantoin in the treatment of chronic urinary tract infections in patients with type 2 diabetes mellitus]. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Role of Old Antibiotics in the Era of Antibiotic Resistance. Highlighted Nitrofurantoin for the Treatment of Lower Urinary Tract Infections. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

General reproduction, perinatal-postnatal, and teratology studies of nitrofurantoin macrocrystals in rats and rabbits. [2013]

7. Austria pubmed.ncbi.nlm.nih.gov

[Treatment of acute urinary tract infection with a nitrofurantoin-sulphadiazine compound preparation (author's transl)]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Systemic Inflammatory Response Syndrome from Nitrofurantoin: A Case Report. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Influence of flocculating agents and structural vehicles on the physical stability and rheological behavior of nitrofurantoin suspension. [2022]