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

NCT02294682 | Completed Phase 2 Results

• 1 other identifier: 116576
• Study Type: interventional
• Target: 106
• Locations: 3 countries
• Sites: 14

Brief 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.

Conditions

Gonorrhea

Keywords

uncomplicated urogenital gonorrhea; Bacterial Type II Topoisomerase Inhibitors (BTI); antibiotics; GSK2140944; N. gonorrhoeae

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Culture-confirmed Bacterial Eradication of Urogenital Neisseria Gonorrhoeae at the Test-of-Cure Visit

  Pre-treatment urogenital, pharyngeal, and rectal swab specimens were obtained for bacteriological culture for neisseria (N.) gonorrhoeae at the Baseline visit. Test- of-Cure was defined by infection site (that is urogenital and, as appropriate, rectal and/or pharyngeal) as culture confirmed bacterial eradication of N. gonorrhoeae observed 3 to 7 days post-treatment. Pre-treatment urogenital specimens were obtained for nucleic acid amplification test (NAAT) assay to detect the presence of N. gonorrhoeae and chlamydia trachomatis at the Baseline visit. Only participants who had a pre-therapy N. gonorrhoeae isolate recovered from their urogenital specimen were evaluated. Microbiologically evaluable (ME) Population comprised of all randomized participants who had N. gonorrhoeae isolated from Baseline cultures of urogenital swab specimens, received any dose of gepotidacin, and returned for their TOC visit.

  Baseline (Day 1, pre-dose) and Test-of-Cure visit (Day 4 to 8)

Secondary Outcomes (17)

• Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

  From start of the study treatment until Test-of-Cure visit (Day 4 to 8)

• Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points

  Baseline visit (Day 1) and Day 4 to Day 8

• Change From Baseline in Pulse Rate at the Indicated Time Points

  Baseline visit (Day 1) and Day 4 to Day 8

• Change From Baseline in Temperature at the Indicated Time Points

  Baseline visit (Day 1) and Day 4 to Day 8

• Change From Baseline in Respiratory Rate at the Indicated Time Points

  Baseline visit (Day 1) and Day 4 to Day 8

Study Arms (2)

GSK2140944 1500 mg

EXPERIMENTAL

Subjects will receive single oral dose of GSK2140944 1500 mg.

Drug: GSK2140944

GSK2140944 3000 mg

EXPERIMENTAL

Subjects will receive single oral dose of GSK2140944 3000 mg.

Drug: GSK2140944

Interventions

GSK2140944 DRUG

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).

GSK2140944 1500 mg; GSK2140944 3000 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (14)

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

Los Angeles, California, 90028, United States

Location

GSK Investigational Site

Los Angeles, California, 90069, United States

Location

GSK Investigational Site

Palm Springs, California, 92262, United States

Location

GSK Investigational Site

San Francisco, California, 94103, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30308, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70119, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68114, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44109, United States

Location

GSK Investigational Site

Jenkintown, Pennsylvania, 19046, United States

Location

GSK Investigational Site

San Juan, 00927, Puerto Rico

Location

GSK Investigational Site

London, SW10 9NH, United Kingdom

Location

Related Publications (3)

• Scangarella-Oman NE, Hossain M, Perry CR, Tiffany C, Powell M, Swift B, Dumont EF. Dose selection for a phase III study evaluating gepotidacin (GSK2140944) in the treatment of uncomplicated urogenital gonorrhoea. Sex Transm Infect. 2023 Feb;99(1):64-69. doi: 10.1136/sextrans-2022-055518. Epub 2022 Nov 21.

  PMID: 36411033 DERIVED

• Scangarella-Oman NE, Hossain M, Dixon PB, Ingraham K, Min S, Tiffany CA, Perry CR, Raychaudhuri A, Dumont EF, Huang J, Hook EW 3rd, Miller LA. Microbiological Analysis from a Phase 2 Randomized Study in Adults Evaluating Single Oral Doses of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2018 Nov 26;62(12):e01221-18. doi: 10.1128/AAC.01221-18. Print 2018 Dec.

  PMID: 30249694 DERIVED

• Taylor SN, Morris DH, Avery AK, Workowski KA, Batteiger BE, Tiffany CA, Perry CR, Raychaudhuri A, Scangarella-Oman NE, Hossain M, Dumont EF. Gepotidacin for the Treatment of Uncomplicated Urogenital Gonorrhea: A Phase 2, Randomized, Dose-Ranging, Single-Oral Dose Evaluation. Clin Infect Dis. 2018 Aug 1;67(4):504-512. doi: 10.1093/cid/ciy145.

  PMID: 29617982 DERIVED

MeSH Terms

Conditions

Gonorrhea

Interventions

gepotidacin

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 19, 2014
• Study Start: April 15, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 27, 2016
• Last Updated: May 23, 2017
• Results First Posted: May 23, 2017

Record last verified: 2017-02

Locations

US (12); PR (1); GB (1)