A Dose-Ranging Study Evaluating the Efficacy, Safety, and Tolerability of GSK2140944 in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae

Gonorrhea Clinical Trial

Official title:

A Phase II, Randomized, Multicenter, Dose-Ranging Study in Adult Subjects Evaluating the Efficacy, Safety, and Tolerability of Single Doses of GSK2140944 in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02294682
• Other study ID #: 116576
• Status: Completed
• Phase: Phase 2
• First received: November 17, 2014
• Last updated: January 16, 2017
• Start date: April 2015
• Est. completion date: July 2016

Study information

• Verified date: January 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GSK2140944 has demonstrated in vitro activity against Neisseria (N.) gonorrhoeae, including ciprofloxacin resistant and susceptible strains. This study is a Phase II, randomized, multicenter, open-label, dose ranging study designed to inform the optimal oral dose of GSK2140944 by further characterizing the efficacy, safety, and tolerability in subjects with uncomplicated urogenital gonorrhea due to N. gonorrhoeae. Subjects will be randomly assigned to receive either a single 1500 milligrams (mg) or 3000 mg oral dose of GSK2140944. Appropriate safety and microbiological assessments will be conducted at the Baseline (Day 1) Visit and repeated at the Test-of-Cure (Day 4 to 8) Visit. The study duration will be approximately 1 week. Approximately 60 microbiologically evaluable subjects (30 subjects in each treatment arm) will complete the study if both arms remain active throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The subject is an adult male or female at least 18 years of age at the time of signing informed consent who meets one of the following criteria:

1. A non-pregnant, non-lactating female of childbearing potential who 1) is sexually inactive by abstinence, 2) has a sole male partner who has been sterilized, or 3) uses a contraceptive method with a failure rate of <1% through the Test-of-Cure Visit. Females of childbearing potential must not become pregnant during the study.

2. A female of non-childbearing potential, which includes the following: Females who are surgically sterile with a documented hysterectomy and/or bilateral oophorectomy; Females with documented tubal ligation. If the procedure was done hysteroscopically, the effectiveness of tubal occlusion must have been documented by hysterosalpingogram after the procedure (typically 3 months after the procedure); Females who are post-menopausal, defined as amenorrhoeic for greater than 1 year. For women whose menopausal status is in doubt, documented previous confirmatory blood samples with follicle-stimulating hormone >40 milli international units (mIU)/millilitre (mL) and estradiol <40 picograms (pg)/mL (<140 picomoles [pmol]/litre [L]) will need to be confirmed, or they will be required to use one of the acceptable contraception methods. Note: For the purposes of these criteria, "documented" includes information obtained via a verbal interview with the subject or from the subject's medical records.

• There is clinical suspicion that the subject has a urogenital gonococcal infection (e.g., prior culture, nucleic acid amplification test [NAAT] or Gram stain presumptive or positive for the presence of N. gonorrhoeae, or sexual contact with a partner diagnosed with gonorrhea within the past 14 days, as reported by the subject). Note: All subjects will be tested for N. gonorrhoeae, but these results will not be used to determine subject eligibility for enrollment in the study.

• The subject has provided written, dated, informed consent and is willing and able to comply with the study protocol.

Exclusion Criteria:

• The subject is pregnant or nursing.

• The subject is a hysterectomized female without a cervix.

• The subject is a male with a current diagnosis of epididymitis or orchitis at the time of the Baseline Visit.

• The subject has a body mass index >=40.0 kilograms (kg)/square meter (m^2).

• The 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.

• The subject has a medical condition or requires medication that may be aggravated by inhibition of acetylcholinesterase, such as: Poorly controlled asthma or chronic obstructive pulmonary disease at baseline and, in the opinion of the investigator, is not stable on current therapy; Acute severe pain, uncontrolled with conventional medical management; Active peptic ulcer disease; Parkinson's disease; Myasthenia gravis; A history of seizure disorder requiring medications for control. This does not include a history of childhood febrile seizures; Any evidence of mechanical obstruction of the urinary or digestive tracks.

• The subject has had any past history or current diagnosis of Clostridium difficile infection at the time of the Baseline Visit.

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

• The subject has a history of sensitivity to the study medication, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

• The subject has a PR interval <120 or >220 milliseconds (msec). Note: Subjects without an evaluable PR interval (e.g., stable atrial fibrillation) are not eligible for this study.

• The subject has a corrected QT (QTc) >450 msec or a QTc >480 msec for subjects with bundle branch block. Note: The QTc is the QT interval corrected for heart rate according to either Bazett formula (QTcB), Fridericia formula (QTcF), machine, or manual overread.

• The subject has QRS duration <70 or >120 msec.

• The subject has pre-existing Grade II atrioventricular block or higher or a history of significant vasovagal and/or syncopal episodes or episodes of symptomatic bradycardia.

• The subject has a current or chronic history of liver disease (with the exception of Gilbert's syndrome), including symptomatic viral hepatitis and moderate to severe liver insufficiency (Child Pugh class B or C).

• The subject has been previously enrolled in this study or has previously been treated with GSK2140944.

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

• The subject has the following gonococcal infections: Suspected or confirmed pelvic inflammatory disease; Suspected or confirmed gonococcal arthritis; Other evidence of disseminated gonococcal infection.

• The subject has received treatment with a systemic or intravaginal antibacterial within 14 days of study entry.

• Subject is taking a medication that has a known risk of torsades de pointes.

Related Conditions & MeSH terms

• Gonorrhea

Intervention

Drug:
• GSK2140944
Immediate release capsules (pink hard gelatin size 00 capsule, with no external marking, filled with slightly agglomerated pale yellowish to grayish yellow powder) containing GSK2140944 500 mg and inactive formulation excipients. GSK2140944 will be administered orally once 1500 mg (3 capsules) or 3000 mg (6 capsules).

Locations

Country	Name	City	State
Puerto Rico	GSK Investigational Site	San Juan
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jenkintown	Pennsylvania
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Culture-confirmed bacterial eradication of urogenital N. gonorrhoeae at the Test-of-Cure Visit	Pre-treatment urogenital, pharyngeal, and rectal swab specimens will be obtained for bacteriological culture for N. gonorrhoeae at the Baseline Visit. "Test of Cure" will be defined by infection site (i.e., urogenital and, as appropriate, rectal and/or pharyngeal) as culture confirmed bacterial eradication of N. gonorrhoeae observed 3 to 7 days post-treatment.	Baseline and Test-of-Cure Visit (Day 4 to 8)
Secondary	Number of subjects with adverse events (AEs)	An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Day 1 to Day 8
Secondary	Vital sign assessments	Vital sign assessments will include temperature, systolic and diastolic blood pressure, pulse rate and respiratory rate.	Day 1 to Day 8
Secondary	Clinical laboratory assessments	Clinical laboratory assessments will include hematology, clinical chemistry and urinalysis parameters.	Day 1 to Day 8
Secondary	Physical examinations	Physical examinations will include assessments of the respiratory, cardiovascular, abdomen, gastrointestinal, urogenital systems, as well as pharyngeal and rectal examinations.	Day 1 to Day 8
Secondary	Electrocardiogram (ECG) assessments	A single 12-lead ECG will be obtained at each time point during the study, using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals.	Day 1 to Day 8