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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04010539




Registration number
NCT04010539
Ethics application status
Date submitted
2/07/2019
Date registered
8/07/2019
Date last updated
13/11/2020

Titles & IDs
Public title
A Study Evaluating Efficacy and Safety of Gepotidacin Compared With Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea
Scientific title
A Phase III, Randomized, Multicenter, Open-Label Study in Adolescent and Adult Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae
Secondary ID [1] 0 0
116577
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gonorrhea 0 0
Condition category
Condition code
Infection 0 0 0 0
Sexually transmitted infections
Reproductive Health and Childbirth 0 0 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Gepotidacin
Treatment: Drugs - Ceftriaxone
Treatment: Drugs - Azithromycin

Active Comparator: Gepotidacin - Subjects will receive Gepotidacin orally at the study site during the Baseline (Day 1) visit followed by self-administration of a second oral dose as an outpatient 6 to 12 hours after the first dose.

Active Comparator: Ceftriaxone plus Azithromycin - Subjects will receive a single IM dose of Ceftriaxone plus a single oral dose of Azithromycin at the study site during the Baseline (Day 1) visit.


Treatment: Drugs: Gepotidacin
Gepotidacin will be administered as 3000 milligram (mg) oral dose (4 X 750 mg tablets) at the study site followed by 3000 mg oral dose (4 X 750 mg tablets) as an outpatient. Each dose should be taken after food consumption and with water.

Treatment: Drugs: Ceftriaxone
Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site.

Treatment: Drugs: Azithromycin
Azithromycin will be administered as 1000 mg oral dose (2 X 500 mg tablets) at the study site. Dose should be taken after food consumption and with water.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the urogenital site at the Test-of-Cure (TOC) - Pre-treatment urogenital swab specimen will be obtained for bacteriological culture for N. gonorrhoea. Test-of-Cure is defined by urogenital site as culture-confirmed bacterial eradication of N. gonorrhoea observed 3 to 7 days post-treatment.
Timepoint [1] 0 0
Up to Day 8
Secondary outcome [1] 0 0
Number of subjects with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the rectal site at the TOC - Pre-treatment rectal swab specimen will be obtained for bacteriological culture for N. gonorrhoea. Test-of-Cure is defined by rectal site as culture-confirmed bacterial eradication of N. gonorrhoea observed 3 to 7 days post-treatment.
Timepoint [1] 0 0
Up to Day 8
Secondary outcome [2] 0 0
Number of subjects with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the pharyngeal site at the TOC - Pre-treatment pharyngeal swab specimen will be obtained for bacteriological culture for N. gonorrhoea. Test-of-Cure is defined by pharyngeal site as culture-confirmed bacterial eradication of N. gonorrhoea observed 3 to 7 days post-treatment
Timepoint [2] 0 0
Up to Day 8
Secondary outcome [3] 0 0
Number of subjects with treatment-emergent adverse events and serious adverse events (SAEs) - An adverse event (AE) is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect, any other situation that require medical or scientific judgment.
Timepoint [3] 0 0
Up to Day 21
Secondary outcome [4] 0 0
Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count - Blood samples will be collected for the assessment of neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count. All parameters have "Giga cells per Liter" as unit of measure.
Timepoint [4] 0 0
Baseline and up to Day 8
Secondary outcome [5] 0 0
Change from Baseline in hemoglobin level - Blood samples will be collected for the assessment of hemoglobin level.
Timepoint [5] 0 0
Baseline and up to Day 8
Secondary outcome [6] 0 0
Change from Baseline in hematocrit level - Blood samples will be collected for the assessment of hematocrit level.
Timepoint [6] 0 0
Baseline and up to Day 8
Secondary outcome [7] 0 0
Change from Baseline in red blood cell (RBC) count - Blood samples will be collected for the assessment of RBC count.
Timepoint [7] 0 0
Baseline and up to Day 8
Secondary outcome [8] 0 0
Change from Baseline in mean corpuscular hemoglobin (MCH) - Blood samples will be collected for the assessment of MCH.
Timepoint [8] 0 0
Baseline and up to Day 8
Secondary outcome [9] 0 0
Change from Baseline in mean corpuscular volume (MCV) - Blood samples will be collected for the assessment of MCV.
Timepoint [9] 0 0
Baseline and up to Day 8
Secondary outcome [10] 0 0
Change from Baseline in blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium and potassium levels - Blood samples will be collected for the assessment of blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium and potassium levels. All parameters have "Millimole per Liter" as unit of measure.
Timepoint [10] 0 0
Baseline and up to Day 8
Secondary outcome [11] 0 0
Change from Baseline in total bilirubin, direct bilirubin and creatinine levels - Blood samples will be collected for the assessment of total bilirubin, direct bilirubin and creatinine levels. All parameters have "Micromoles per liter" as unit of measure.
Timepoint [11] 0 0
Baseline and up to Day 8
Secondary outcome [12] 0 0
Change from Baseline in albumin and total protein levels - Blood samples will be collected for the assessment of albumin and total protein levels. All parameters have "Gram per liter" as unit of measure.
Timepoint [12] 0 0
Baseline and up to Day 8
Secondary outcome [13] 0 0
Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels - Blood samples will be collected for the assessment of AST, ALT and alkaline phosphatase levels. All parameters have "International units per Liter" as unit of measure.
Timepoint [13] 0 0
Baseline and up to Day 8
Secondary outcome [14] 0 0
Number of subjects with abnormal urinalysis Dipstick results - Urine samples will be collected to assess pH, glucose, protein, blood and ketones by Dipstick method.
Timepoint [14] 0 0
Up to Day 8
Secondary outcome [15] 0 0
Change from Baseline in specific gravity of urine - Urine samples will be collected for the measurement of specific gravity.
Timepoint [15] 0 0
Baseline and up to Day 8
Secondary outcome [16] 0 0
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) - SBP and DBP will be assessed in the semi-supine position after 5 minutes rest.
Timepoint [16] 0 0
Baseline and up to Day 8
Secondary outcome [17] 0 0
Change from Baseline in pulse rate - Pulse measurements will be assessed in the semi-supine position after 5 minutes rest.
Timepoint [17] 0 0
Baseline and up to Day 8
Secondary outcome [18] 0 0
Change from Baseline in body temperature - Changes in body temperature from Baseline will be assessed.
Timepoint [18] 0 0
Baseline and up to Day 8

Eligibility
Key inclusion criteria
- Subjects must be >=12 years of age at the time of signing the informed consent.

- Subjects having body weight of >45 kilogram (kg).

- Subjects having clinical suspicion of a urogenital gonococcal infection with or
without pharyngeal and/or rectal gonococcal infection and have one of the following: a
prior positive culture for Neisseria gonorrhoeae from up to 5 days before screening
(as long as the subject has not received any treatment for this infection) or a Gram
stain (urogenital specimens only) positive or presumptive for Gram-negative
intracellular diplococci from up to 5 days before screening (as long as the subject
has not received any treatment for this infection) or a prior positive nucleic acid
amplification test assay for Neisseria gonorrhoeae from up to 7 days before screening
(as long as the subject has not received any treatment for this infection).

- Subjects who are willing to avoid anal, oral, and vaginal sexual intercourse or use
condoms for all forms of intercourse from the Baseline Visit through the TOC Visit.

- Male or female subjects having his or her original urogenital anatomy at birth.

- Male subject must agree to use contraception (male condoms) during intercourse from
the Baseline Visit through completion of the TOC Visit.

- Female subject is eligible to participate if she is not pregnant, not breastfeeding,
and at least 1 of the following conditions applies: Not a woman of childbearing
potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance (male
partners of WOCBP must use a male condom during intercourse) from the Baseline Visit
through completion of the TOC Visit.

- Subjects who are capable of giving signed informed consent or assent, which includes
compliance with the requirements and restrictions listed in the informed consent form
(ICF) or assent form and in study protocol.
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Male subjects with a current diagnosis of epididymitis and/or orchitis at the time of
the Baseline Visit.

- Subject who is suspected or confirmed to have a Chlamydia trachomatis infection and
per the investigator's judgement standard-of-care treatment for this infection cannot
be safely postponed until the TOC Visit.

- Subject has a body mass index >=40 kilogram per square meter (kg/m^2) or has a body
mass index >=35.0 kg/m^2 and is experiencing obesity-related health conditions such as
high blood pressure or diabetes.

- Subject has a history of sensitivity to the study treatments, or components thereof,
or a history of a drug (including erythromycin and any macrolide or ketolide drug) or
other allergy that, in the opinion of the investigator or medical monitor,
contraindicates his or her participation.

- Subject is immunocompromised or has altered immune defenses that may predispose the
subject to a higher risk of treatment failure and/or complications. For example,
subjects with diabetes, renal transplant recipients, subjects with clinically
significant persistent granulocytopenia (absolute neutrophil count <1000 per
microliter [µL]) and subjects receiving immunosuppressive therapy, including
corticosteroid therapy (>40 mg per day prednisolone or equivalent for >1 week, >=20 mg
per day prednisolone or equivalent for >2 weeks, or prednisolone or equivalent >=10 mg
per day for >6 weeks). Subjects with a known cluster of differentiation 4 (CD4) count
of <200 cells per cubic millimeter (cells/mm^3) should not be enrolled.

- Subject has a medical condition that requires medication that may be impacted by
inhibition of acetylcholinesterase, such as, poorly controlled asthma or chronic
obstructive pulmonary disease at the Baseline Visit and, in the opinion of the
investigator, not stable on current therapy, acute severe pain, uncontrolled with
conventional medical management, active peptic ulcer disease, Parkinson disease,
Myasthenia gravis, a history of seizure disorder requiring medications for control
(this does not include a history of childhood febrile seizures) or subject has any
surgical or medical condition (active or chronic) that may interfere with drug
absorption, distribution, metabolism, or excretion of the study treatment (For
example., ileostomy or malabsorption syndrome).

- Subject has known anuria, oliguria, or severe impairment of renal function (creatinine
clearance <30 milliliter per minute [mL/min] or clinically significant elevated serum
creatinine as determined by the investigator).

- Subject in the judgment of the investigator, would not be able or willing to comply
with the protocol or complete study follow-up.

- Subject has a serious underlying disease that could be imminently life threatening, or
the subject is unlikely to survive for the duration of the study period.

- Subject has congenital long QT syndrome or known prolongation of corrected QT interval
(QTc).

- Subject has uncompensated heart failure.

- Subject has severe left ventricular hypertrophy.

- Subject has a family history of QT prolongation or sudden death.

- Subject has a recent history of vasovagal syncope or episodes of symptomatic
bradycardia or bradyarrhythmia within the last 12 months.

- With the exception of azithromycin study treatment, the subject 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 his or her
Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC
Visit; or the subject is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor
or a strong P-glycoprotein (P-gp) inhibitor.

- For any subject >=12 to <18 years, the subject has an abnormal electrocardiogram (ECG)
reading.

- The subject has a QTc >450 millisecond (msec) or a QTc >480 msec for subjects with
bundle-branch block.

- Subject has a documented or recent history of uncorrected hypokalemia within the past
3 months.

- Subject has a known history of cholestatic jaundice or hepatic dysfunction associated
with prior use of azithromycin.

- Subject has a known alanine aminotransferase (ALT) value >2 times upper limit of
normal (ULN).

- Subject 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%).

- Subject 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).

- Subject has been previously enrolled in this study or has previously been treated with
Gepotidacin.

- Subject has participated in a clinical trial and has received an investigational
product within 30 days or 5 half-lives, whichever is longer.

- Subject has any of the following gonococcal infections that require a different dose
or duration of treatment: suspected or confirmed pelvic inflammatory disease or
suspected or confirmed gonococcal arthritis or suspected or confirmed gonococcal
conjunctivitis or suspected or confirmed gonococcal endocarditis or other evidence of
disseminated gonococcal infection.

- Subject has received any antibacterial therapy for the treatment of a gonococcal
infection within 14 days before the Baseline Visit.

- Subject has received any systemic, topical, or intravaginal antibiotics or any
systemic antifungals within 7 days before the Baseline Visit.

- Subject must not use St John's wort or ergot derivatives from within 14 days before
the Baseline Visit through the TOC Visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
GSK Investigational Site - Surry Hills
Recruitment hospital [4] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [5] 0 0
GSK Investigational Site - Fortitude Valley
Recruitment hospital [6] 0 0
GSK Investigational Site - Southport
Recruitment hospital [7] 0 0
GSK Investigational Site - Carlton
Recruitment hospital [8] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [9] 0 0
GSK Investigational Site - North Fitzroy
Recruitment hospital [10] 0 0
GSK Investigational Site - Prahran
Recruitment hospital [11] 0 0
GSK Investigational Site - Fremantle
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Surry Hills
Recruitment postcode(s) [4] 0 0
2000 - Sydney
Recruitment postcode(s) [5] 0 0
4006 - Fortitude Valley
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
3053 - Carlton
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
3068 - North Fitzroy
Recruitment postcode(s) [10] 0 0
3181 - Prahran
Recruitment postcode(s) [11] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Germany
State/province [10] 0 0
Bayern
Country [11] 0 0
Germany
State/province [11] 0 0
Hessen
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Germany
State/province [13] 0 0
Hamburg
Country [14] 0 0
Germany
State/province [14] 0 0
München
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Sevilla
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Birmingham
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Leeds
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
St Helens

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase III, randomized, multicenter, open-label study which will be performed to
evaluate efficacy and safety of oral Gepotidacin compared to intramuscular (IM) ceftriaxone
plus oral azithromycin for the treatment of uncomplicated urogenital infection caused by
Neisseria gonorrhoeae in adolescent and adult subjects. In this study, subjects will be
randomly assigned to receive either oral gepotidacin or IM ceftriaxone plus oral
azithromycin. Approximately 600 subjects will be randomized to receive study treatment. The
duration of the study will be approximately 21 days.
Trial website
https://clinicaltrials.gov/show/NCT04010539
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04010539