CTRI/2020/01/022715 [Registered on: 13/01/2020] Trial Registered Prospectively
Last Modified On:
13/01/2020
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
’This research study is being done to learn more about bladder infections also known as acute cystitis or uncomplicated urinary tract infection (uUTI), and if a new medicine called gepotidacin can be used for this infection
Scientific Title of Study
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)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
204989_Version dated 12 April 2019
Protocol Number
NCT04020341
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Rashmi Chitgupi
Designation
Associate Director - Clinical Management
Affiliation
PPD Pharmaceutical Development India Private
Address
PPD Pharmaceutical Development India Private Limited, 101, A
Wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri
East, Mumbai
Mumbai (Suburban)
MAHARASHTRA
400099
Mumbai (Suburban) MAHARASHTRA 400099 India
Phone
912266022900
Fax
912266022999
Email
Rashmi.Chitgupi@ppdi.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Associate Director - Clinical Management
Affiliation
PPD Pharmaceutical Development India Private
Address
PPD Pharmaceutical Development India Private Limited, 101, A
Wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri
East, Mumbai
Mumbai (Suburban)
MAHARASHTRA
400099
Mumbai MAHARASHTRA 400099 India
Phone
912266022900
Fax
912266022999
Email
Rashmi.Chitgupi@ppdi.com
Source of Monetary or Material Support
GlaxoSmithKline Research and Development Limited
980 Great West Road
Brentford
Middlesex TW8 9GS UK
Primary Sponsor
Name
GlaxoSmithKline Research and Development Limited
Address
GlaxoSmithKline Research and Development Limited
980 Great West Road
Brentford
Middlesex TW8 9GS UK
Type of Sponsor
Other [Commercial]
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Bulgaria Germany Greece Hungary India Mexico Romania Spain United Kingdom United States of America
Sites of Study
No of Sites = 8
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Shital Kapadia
B. J. Medical College & Civil Hospital
B. J. Medical College & Civil Hospital,Department of OBGYN
Asarwa, Ahmedabad-380016
Gujarat, India
Ahmadabad GUJARAT
07925464389 07925464389 sheetalobgy@gmail.com
Dr Vineet Narang
Indian Spinal Injuries Centre
Indian Spinal Injuries Centre,Department of urology, Ground Floor, room no. 21, Sec - C, Vasant Kunj, New Delhi 110070, India
New Delhi DELHI
01142255225 01126898810 drvineetnarang@gmail.com
Dr Sanjay Pandey
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, 2nd Floor, Medical Research Department, Rao Saheb Achutrao Patwardhan Marg, Four Bunglows, Andheri West, Mumbai- 400053 Mumbai MAHARASHTRA
SMS Medical College and attached Hospital, Department of Nephrology
Romm No.63,JLN marg,Jaipur, Rajasthan,302004, India Jaipur RAJASTHAN
01412366494 01412366494 dhananjaynephro@gmail.com
Dr Singh Indu
Surya Super Speciality Hospital
Surya Super Speciality Hospital
A unit if G.V Meditech Pvt. Ltd,Clinical Trial Department,B38/46H,Tulsipur, Near Akashwani,Mahmoorganj, Varanasi-221010 Uttar-Pradesh, India
Varanasi UTTAR PRADESH
9335092858 9335092858 indusingh.gvm@gmail.com
Details of Ethics Committee
No of Ethics Committees= 8
Name of Committee
Approval Status
Ethics Committee, SMS Medical College and Attached Hospitals
Institutional Ethics Committee for Human Research Medical College Baroda (IECHR)
Submittted/Under Review
Institutional Ethics Committee,B. J. Medical College & Civil Hospital
Submittted/Under Review
Nirmal Hospital Pvt. Ltd. Ethics Committee
Approved
Paras Hospital Ethics Committee
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: N390||Urinary tract infection, site notspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Gepotidacin
Drug: Gepotidacin
Gepotidacin will be available as tablets containing 750 mg gepotidacin. Each dose should be taken with water after consumption of food.
Subjects will be administered oral doses of 1500 mg gepotidacin plus nitrofurantoin matching placebo twice daily (BID); approximately every 12 hours for 5 days
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
Comparator Agent
Nitrofurantoin
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.
Subjects will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.
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.
Inclusion Criteria
Age From
12.00 Year(s)
Age To
50.00 Year(s)
Gender
Female
Details
Age and Weight
1.The participant is ≥12 years of age at the time of signing the informed consent/assent and has a body weight ≥40 kg.
Note: Although participants as young as 12 years may enroll in the study, study sites must follow their institutional ethics committee and local country/national regulatory guidelines and enrollment will be contingent upon such approvals regarding the allowed lower age limit for clinical study participants.
Type of Participant and Disease Characteristics
2.The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset ≤72 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain .
3.The participant has nitrite or pyuria (>15 WBC/HPF or the presence of 3+/moderate leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
Sex
4.The participant is female. A female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least 1 of the following conditions applies:
(a)Not a woman of childbearing potential (WOCBP) as defined in
OR
(b)A WOCBP who agrees to follow the contraceptive guidance in from the Baseline Visit through completion of the TOC Visit.
Informed Consent
5.The participant is capable of giving signed informed consent/assent as described in , which includes compliance with the requirements and restrictions listed in the informed consent form (ICF)/assent form and in this protocol.
ExclusionCriteria
Details
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions and History
1.The participant resides in a nursing home or dependent care type-facility.
2.The participant has a body mass index ≥40.0 kg/m2 or a body mass index ≥35.0 kg/m2 and is experiencing obesity-related health conditions such as high blood pressure or uncontrolled diabetes.
3.The 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.
4.The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications (e.g., uncontrolled diabetes, renal transplant recipients, participants with clinically significant persistent granulocytopenia [absolute neutrophil count <1000/µL], and participants receiving immunosuppressive therapy, including corticosteroid therapy [>40 mg/day prednisolone or equivalent for >1 week, ≥20 mg/day prednisolone or equivalent for >2 weeks, or prednisolone or equivalent ≥10 mg/day for >6 weeks]). Participants with a known CD4 count of <200 cells/mm3 should not be enrolled.
5.The participant has any of the following:
a)Medical condition that requires medication that may be impacted by inhibition of acetylcholinesterase, such as:
b)Poorly controlled asthma or chronic obstructive pulmonary disease at Baseline and, in the opinion of the investigator, not stable on current therapy
c)Acute severe pain, uncontrolled with conventional medical management
d)Active peptic ulcer disease
e)Parkinson disease
f)Myasthenia gravis
g)A history of seizure disorder requiring medications for control (this does not include a history of childhood febrile seizures)
OR
h)Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment (e.g., ileostomy or malabsorption syndrome).
6.The participant has a known glucose-6-phosphate dehydrogenase deficiency.
7.The participant, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.
8.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.
Urinary Tract Infection/Renal/Urogenital Exclusions
9.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 Enterobacteriaceae (other than E. coli) as the contributing pathogen.
10.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.
11.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 (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).
12.The participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
13.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°F, flank pain, chills, or any other manifestations suggestive of upper UTI.
14.The participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance <60 mL/min or clinically significant elevated serum creatinine as determined by the investigator).
15.The participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
Cardiac Exclusions
16.The participant has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
17.The participant has uncompensated heart failure.
18.The participant has severe left ventricular hypertrophy.
19.The participant has a family history of QT prolongation or sudden death.
20.The participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady arrhythmia within the last 12 months.
21.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 or a strong P-glycoprotein (P-gp) inhibitor.
Cardiac ECG Exclusions
22.For any participant ≥12 to <18 years of age, the participant has an abnormal electrocardiogram (ECG) reading.
23.The participant has a QTc >450 msec or a QTc >480 msec for participants with bundle-branch block.
Note: The QTc is the QT interval corrected for heart rate according to either Bazett
(QTcB) or Fridericia (QTcF) formula, machine, or manual overread.
24.The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months
Hepatic Exclusions
25.The participant has a known alanine aminotransferase (ALT) value >2 × upper limit of normal (ULN).
26.The participant has a known bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
27.The 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).
Note: Participants with asymptomatic viral hepatitis are eligible for study participation.
28.The participant has a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
Prior Antibiotic/Antifungal Use Exclusion
29.The participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
Concomitant Medication Use Exclusion
30.The participant must agree not to use the medications or nondrug therapies from the
Baseline Visit through the TOC Visit
Prior/Concurrent Clinical Study Experience
31.The participant has been previously enrolled in this study or has previously been treated with gepotidacin.
32.The participant has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
To assess the combined clinical and microbiological efficacy of gepotidacin compared to nitrofurantoin, at the Test-of-Cure (TOC) Visit, in female participants with acute cystitis in the Microbiological Intent-to-Treat nitrofurantoin-Susceptible (micro-ITT NTF-S) Population
Therapeutic response (combined per-participant microbiological and clinical response) at the TOC Visit
Secondary Outcome
Outcome
TimePoints
1.assess the clinical efficacy of gepotidacin compared to nitrofurantoin, at the TOC and Follow-up Visits
2.assess the microbiological efficacy of gepotidacin compared to nitrofurantoin at the TOC and Follow-up Visits
3.assess the therapeutic response of acute cystitis after treatment with gepotidacin or nitrofurantoin, at the Follow-up Visit
4.determine the plasma and urine PK concentrations of gepotidacin
5.assess the safety and tolerability of gepotidacin compared to nitrofurantoin
1.Clinical outcome and response at the TOC (day 10-13)and Follow-up Visits(Day 28±3)
2.Microbiological outcome and response at the TOC(day 10-13) and Follow-up Visits(Day 28±3)
3.Therapeutic response at the Follow-up Visit(Day 28±3)
4.Gepotidacin plasma and urine concentrations (peak and trough)
5.Treatment-emergent AEs and serious AEs (SAEs) and change from baseline results for clinical laboratory tests and vital sign measurements
Target Sample Size
Total Sample Size="1200" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
15/01/2020
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
01/10/2019
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="0" Days="28"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
After completion of the study, the data may be considered for reporting at a scientific meeting or for
publication in a scientific journal. In these cases, the GSK. will be responsible for these
activities and will work with the investigators to determine how the manuscript is written and edited,
the number and order of authors, the publication to which it will be submitted, and other related issues.GSK. has final approval authority over all such issues. Data are the
property of the GSK. and cannot be published without prior authorization from the
GSK, but data and publication thereof will not be unduly withheld.All GSK studies are published in peer reviewed journals & submitted by 18 months LSLV
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Study 204989 is a Phase III, randomized, multicenter, parallel-group, double-blind, double-dummy, comparator-controlled, noninferiority study in adolescent and adult female participants comparing the efficacy and safety of oral gepotidacin to oral nitrofurantoin in the treatment of uncomplicated UTI (acute cystitis).Participants will be stratified by age category and acute cystitis recurrence and will be randomly assigned in a 1:1 ratio to receive either oral gepotidacin or oral nitrofurantoin.Appropriate safety, efficacy, and microbiological assessments will be conducted at the Baseline (Day 1) Visit and repeated at the On-therapy (Day 2 to 3), TOC (Day10 to 13), and Follow-up (Day 28±3) Visits. Pharmacokinetic samples will be collected at the Baseline and On-therapy Visits. The UTI Activity Impairment Assessment (AIA) will be completed at each visit.For the primary efficacy endpoint of therapeutic response (combined per-participant microbiological and clinical response), therapeutic success refers to participants who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens [e.g., 105 colony-forming units/mL (CFU/mL)] recovered at Baseline to <103 CFU/mL as observed on quantitative urine culture) without the participant receiving other systemic antimicrobials 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) at the TOC Visit in the micro-ITT NTF-S Population.
Number of Participants: The study will enroll approximately 1000 to 1200 participants to obtain approximately 768 evaluable participants with acute cystitis in the micro-ITT NTF-S Population, for an estimated total of approximately 384 evaluable participants per treatment group. Enrollment will continue until the approximate target number of participants in the micro-ITT NTF-S Population has been reached.
Treatment Groups and Duration: Participants will receive 1 of the following treatments: Gepotidacin: 1500 mg administered orally twice daily for 5 days (Note: Each dose should be taken after food consumption and with water to assist with tolerability.) Nitrofurantoin: 100 mg administered orally twice daily for 5 days (Note: Each dose should be taken after food consumption and with water.) The study duration is approximately 28 days with 4 planned study visits: Baseline (Day 1) Visit On-therapy (Day 2 to 3) Visit TOC (Day 10 to 13) Visit Follow-up (Day 28±3) Visit