Safety, Tolerability, Pharmacokinetic and Microbiological Investigation of GSK3882347 in Female Participants With Urinary Tract Infections

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05138822
• Collaborator: (none)
• Enrollment: 80
• Locations: 3
• Arms: 2
• Anticipated Duration (Months): 13.2
• Patients Per Site: 26.7
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This phase 1b study is a double-blind, double-dummy, nitrofurantoin-controlled study designed to evaluate microbiological response at the test of cure (ToC) visit along with safety, tolerability and pharmacokinetic (PK) response following daily oral dosing for 5 days of GSK3882347 in an adult female with uncomplicated urinary tract infections (uUTI). Comparator nitrofurantoin will be included in the study to ensure unbiased reporting of safety events. The study will be separated into 2 cohorts. Cohort 1 consists of an inpatient treatment period and PK analysis at frequent timepoints. Cohort 2 includes an outpatient treatment period and PK analysis conducted less frequently, at key trough timepoints.

Condition or Disease	Intervention/Treatment	Phase
Uncomplicated Urinary Tract Infections	Drug: GSK3882347; Drug: Nitrofurantoin; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This will be a randomized double-blind study and participants will be randomized to receive either GSK3882347 or nitrofurantoin in a 3:1 allocation ratio using an interactive response technology (IRT).This will be a randomized double-blind study and participants will be randomized to receive either GSK3882347 or nitrofurantoin in a 3:1 allocation ratio using an interactive response technology (IRT).
• Masking: Double (Participant, Investigator)
• Masking Description: This will be a randomized double-blind study with both participants and site staff blinded.
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Double Dummy, Randomized, Phase 1b, Nitrofurantoin Controlled, Repeat Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Microbiological Response of GSK3882347 in Female Participants With Acute Uncomplicated Urinary Tract Infection
• Actual Study Start Date: May 18, 2022
• Anticipated Primary Completion Date: Jun 23, 2023
• Anticipated Study Completion Date: Jun 23, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK3882347 + Placebo Participants will be administered GSK3882347 plus placebo.	Drug: GSK3882347; GSK3882347 will be administered on each dosing day.; Drug: Placebo; Placebo matching study drug (GSK3882347) or Nitrofurantoin will be administered on each dosing day.
Active Comparator: Nitrofurantoin+ Placebo Participants will be administered nitrofurantoin plus placebo.	Drug: Nitrofurantoin; Nitrofurantoin will be administered on each dosing day.; Drug: Placebo; Placebo matching study drug (GSK3882347) or Nitrofurantoin will be administered on each dosing day.

Outcome Measures

Primary Outcome Measures

1. Numbers of participants with microbiological response (responder/non-responder of GSK3882347) at the test of cure (TOC) visit [Day 10 to Day 13]

   Microbiological response is defined as the response of less than (<)10^3 colony forming unit (CFU)/milliliter (mL) for all qualifying Escherichia coli (identified at baseline urine microbiology visit) at TOC visit, without receiving other systemic antimicrobials (rescue medications) prior to TOC

Secondary Outcome Measures

1. Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Up to Day 31]

   AEs and SAEs will be collected.

2. Number of participants with clinically significant change from baseline in hematology parameters [Baseline (Day 1) and up to Day 31]

   Blood samples will be collected for the assessment of hematology parameters.

3. Number of participants with clinically significant change from baseline in clinical chemistry [Baseline (Day 1) and up to Day 31]

   Blood samples will be collected for the assessment of chemistry parameters.

4. Number of participants with clinically significant change from baseline in urinalysis [Baseline (Day 1) and up to Day 31]

   Urine samples will be collected for the assessment of urinalysis parameter.

5. Number of participants with clinically significant change from baseline in vital signs [Baseline (Day 1) and up to Day 31]

6. Number of participants with clinically significant change from baseline in 12- lead Electrocardiogram (ECG) findings [Baseline (Day 1) and up to Day 31]

7. Area under the concentration-time curve extrapolated from time zero to infinity (AUC [0-inf]) of GSK3882347 single dose [Day 1]

   Blood samples will be collected for the concentrations of GSK3882347.

8. Maximum plasma concentration (Cmax) of GSK3882347 single dose [Day 1]

   Blood samples will be collected for the concentrations of GSK3882347.

9. Time to Cmax (Tmax) of GSK3882347 single dose [Day 1]

   Blood samples will be collected for the concentrations of GSK3882347.

10. Area under the concentration-time curve from time zero to 24 hours after dosing (AUC [0-24]) repeat dose of GSK3882347 [Up to Day 5]

    Blood samples will be collected for the concentrations of GSK3882347.

11. Cmax of GSK3882347 repeat dose [Up to Day 5]

    Blood samples will be collected for the concentrations of GSK3882347.

12. Tmax of GSK3882347 repeat dose [Up to Day 5]

    Blood samples will be collected for the concentrations of GSK3882347.

13. Pre-dose plasma concentrations over the dosing interval (Ctau) of GSK3882347 [Up to Day 5]

    Blood samples will be collected for the concentrations of GSK3882347.

14. Observed accumulation ratio (Ro) using AUC(0-tau) following repeat dose of GSK3882347 [Up to Day 5]

    Blood samples will be collected for the concentrations of GSK3882347.

15. Time invariance of GSK3882347 using AUC(0-tau) repeat dose [Up to Day 5]

    Blood samples will be collected for the concentrations of GSK3882347.

16. Urine concentrations of GSK3882347 [Up to Day 5]

    Urine samples will be collected for the concentrations of GSK3882347

17. Amount excreted in urine (Ae) of unchanged GSK3882347 [Up to Day 5]

    Urine samples will be collected for the concentrations of GSK3882347.

18. Fraction of the dose excreted in urine (fe) of GSK3882347 [Up to Day 5]

    Urine samples will be collected for the concentrations of GSK3882347.

19. Renal clearance (CLr) of GSK3882347 [Up to Day 5]

    Urine samples will be collected for the concentrations of GSK3882347.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must be greater than or equal to (>=)18 years of age and less than or equal to (<=)70 years.

• The participant has 2 or more of the following clinical signs and symptoms of uncomplicated urinary tract infections (uUTI) with onset less than or equal to (<=) 72 hours of the screening assessment: dysuria, frequency, urgency, or lower abdominal pain.

• Participant has nitrite and pyuria from a pretreatment clean-catch midstream urine sample

• Participants with body mass index (BMI) greater than or equal to (>=) 19.0 kilograms per square meter (kg/m^2).

• 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:

1. Woman participant of non-childbearing potential (WONCBP) Or

2. Woman participant of childbearing potential (WOCBP) using a contraceptive method that is highly effective, with a failure rate of less than (<) 1 percentage (%), during the study intervention period

• 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:

• The participant has a BMI greater to or equal (>=) 40.0 kg/ m^{2 or a BMI >=35.0 kg/ m}2 with obesity related health conditions such as high blood pressure or uncontrolled diabetes (non-fasting glucose value >300 milligram/deciliter [mg/dL]).

• 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 symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis.

• 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 of the urinary tract, primary renal disease, or neurogenic bladder, or the participant has a history of anatomical or functional abnormalities of the urinary tract.

• The participant has an indwelling catheter, nephrostomy, ureteral 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 symptoms onset

=96 hours before the screening assessment, or a temperature >=101 degree Fahrenheit (°F) (>=38 degree Celsius [°C]), flank pain, chills, or any other manifestations suggestive of upper UTI.

• The participant has anuria, oliguria, or significant impairment of renal function.

• The participant presents at enrollment with a suspected sexually transmitted infection.

• A positive confirmation of Coronavirus Disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.

• The participant has received treatment with other systemic antimicrobials or systemic antifungals within 4 weeks before study entry.

• Regular alcohol consumption within 6 months prior to the study with an average weekly intake of >14 units for females and one unit is equivalent to approximately 8 g of alcohol: a half-pint (250 ml) of beer, one glass (125 mL) of wine or one (35 mL) measure of spirits.

• Unable to take nitrofurantoin. E.g. hypersensitivity to the active substance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Anniston	Alabama	United States	36207
2	GSK Investigational Site	La Mesa	California	United States	91942
3	GSK Investigational Site	Chicago	Illinois	United States	60643

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: NCT05138822
• Other Study ID Numbers: 212943
• First Posted: Dec 1, 2021
• Last Update Posted: Jun 30, 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: Microbiological response; Urinary tract infections (UTI); GSK3882347; Nitrofurantoin; Pharmacokinetics; Escherichia coli (E. coli)
• Additional relevant MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Nitrofurantoin

Study Results

No Results Posted as of Jun 30, 2022