Dose-Ranging Study of GSK2140944 in the Treatment of Subjects With Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections

NCT02045797 | Completed Phase 2 Results DMC

• 1 other identifier: 116704
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 30

Brief Summary

GSK2140944 belongs to a novel structural class of antibiotics - Bacterial Type II Topoisomerase Inhibitors (BTI). This is a Phase II, randomized, two-part, multicenter study designed to select the optimal dose by further characterizing the safety, tolerability and PK of GSK 2140944 and by evaluating efficacy in subjects requiring in-patient medical care to treat their suspected or confirmed Gram-positive acute bacterial skin and skin structure infections (ABSSSI). The selected dose will be used in future studies.

Conditions

Infections, Bacterial

Keywords

Dose ranging; Intravenous; Adaptive design; suspected or confirmed gram-positive acute bacterial skin and skin structure infection; Subjects; infection; Oral; GSK2140944

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Composite of the Cure Rate as Measured by Clinical Response and Outcome at the Early Efficacy Visit Combined With Withdrawal Rate

  Cure rate and withdrawal rate data points was jointly assessed in a composite endpoint for all participants who received at least one dose of GSK2140944. Cure rate was defined as the percentage of participants exhibiting clinical improvement (=\>20% reduction in overall lesion area) at the early efficacy visit. Withdrawal rate was defined as the percentage of participants who withdrew from study treatment due to a drug-related adverse event (AE) at any point while on treatment.

  Up to Day 3

Secondary Outcomes (47)

• Number of Participants With Clinical Response and Outcome at Early Efficacy Visit

  Up to Day 3

• Number of Participants With Clinical Response and Outcome at the Post Therapy Visit (Day 12-18)

  Day 12 to Day 18

• Number of Participants With Clinical Response and Outcome at the Final Follow up Visit (Day 21-28)

  Day 21 to Day 28

• Number of Pathogens With Microbiological Response and Outcome at Early Efficacy Visit for Staphylococcus Aureus (SA) Pathogen in Lesion Sample

  Up to Day 3

• Number of Pathogens With Microbiological Response and Outcome at Early Efficacy Visit for Methicillin-resistant Staphylococcus Aureus (MRSA) in Lesion Sample

  Day 3

Study Arms (3)

Treatment Group A

EXPERIMENTAL

Subject will receive GSK2140944 750mg IV every 12 hours (q12h; twice daily \[BID\]) on Day 1 and Day 2. Subject may switch to GSK2140944 1500mg orally (PO) q12h (BID) at investigator's decision or will continue to receive GSK2140944 750mg IV q12h (BID) from Day 3 to Day 10.

Drug: GSK2140944 Lyophile; Drug: GSK2140944 Capsules

Treatment Group B

EXPERIMENTAL

Subject will receive GSK2140944 1000mg IV q12h (BID) on Day 1 and Day 2 . Subject may switch to GSK2140944 2000mg PO q12h (BID) at investigator's decision or will continue to receive GSK2140944 1000mg IV q12h (BID) from Day 3 to Day 10.

Drug: GSK2140944 Lyophile; Drug: GSK2140944 Capsules

Treatment Group C

EXPERIMENTAL

Subject will receive GSK2140944 1000mg IV q8h (TID) on Day 1 and Day 2. Subject may switch to GSK2140944 2000mg PO q8h (TID) at investigator's decision or will continue to receive GSK2140944 1000mg IV q8h (TID) from Day 3 to Day 10.

Drug: GSK2140944 Lyophile; Drug: GSK2140944 Capsules

Interventions

GSK2140944 Lyophile DRUG

GSK2140944 Lyophile (pale yellow to grayish yellow cake) containing 750 mg of GSK2140944 (as free base) per vial for IV infusion.

Treatment Group A; Treatment Group B; Treatment Group C

GSK2140944 Capsules DRUG

GSK2140944 500 mg capsules will be supplied as pink hard gelatin capsule with no external markings filled with slightly agglomerated pale yellow to grayish yellow powder.

Treatment Group A; Treatment Group B; Treatment Group C

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 at least 18 years of age or an adult female at least 18 years of age who meets one of the following criteria: A female of child-bearing potential who is either 1) sexually inactive by abstinence, 2) whose sole male partner has been sterilized, or 3) uses a contraceptive method with a failure rate of \< 1%. Females of child-bearing potential must not become pregnant during the study. A female of non child- bearing potential, which includes: Females who are surgically sterile with a documented hysterectomy and/or bilateral oophorectomy; Females with a documented tubal ligation. If the procedure was done hysteroscopically, the effectiveness of tubal occlusion must have been documented by hysterosalpingogram post procedure (typically 3 months after procedure); Females who are post-menopausal, defined as amenorrhoeic for greater than 1 year. For women whose menopausal status is in doubt, a documented previous confirmatory blood sample with follicle-stimulating hormone (FSH) \> 40 milli-international units per milliliter (MIU/mL) and estradiol \<40 picograms per milliliter (\<140 picomole per liter) would need to be confirmed or they will be required to use one of the contraception methods.
• The subject has a diagnosis of ABSSSI suspected or documented to be caused by Gram-positive pathogens that requires of intravenous (IV) antibiotic treatment for which subjects is willing to receive treatment in an in-patient setting for at least 2 days.. ABSSSI is defined as one of the following: Wound infection (traumatic or post-surgical): an infection involving skin and subcutaneous tissue, characterized by purulent drainage from a wound with surrounding redness, edema, and/or induration of a minimum surface area of 75 square centimeter (cm\^2) (e.g., the shortest distance of redness, edema, and/or induration extending at least 5 centimeter (cm) from the peripheral margin of the wound); Major cutaneous abscess: an infection characterized by a collection of pus within the dermis or deeper that is accompanied by redness, edema, and/or induration of a minimum surface area of 75 cm\^2 (e.g., the shortest distance of redness, edema, and/or induration extending at least 5 cm from the peripheral margin of the abscess). Cellulitis: a diffuse skin infection characterized by a spreading area of redness, edema, and/or induration of a minimum surface area of 75 cm\^2 Note: For subjects with more than one type of eligible lesion/wound or with multiple lesions of the same type, the investigator must clearly identify the lesion to be evaluated for study purposes. The identified lesion must be consistently chosen for assessment (including digital imaging) throughout the study. Incision and drainage (I\&D) of the lesion is permitted prior to the first dose of study medication and will be allowed, per protocol, up to 24 hours after the start of the first dose of study medication.
• The subject has at least 1 additional sign or symptom of skin infection: fluctuation, heat/localized warmth, and pain/tenderness.
• The subject has at least 1 systemic marker of infection at the time of screening: Lymphadenopathy (proximal to and within the drainage of the wound); Fever (\>=38 degrees Celsius); white blood cells (WBC) elevation (\>10000 /cubic millimetre \[mm\^3\] or \>10% immature neutrophils regardless of WBC count); C-reactive protein \> upper limit of normal (ULN). Note: Systemic markers of infection are not required for subjects \>70 years of age or for known or suspected (based on blood glucose levels) diabetics.
• 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 has an immune-compromising illness; including known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), organ (including bone marrow) transplant recipients, hematological malignancy, and immunosuppressive therapy, including high-dose corticosteroids (e.g., greater than 40mg prednisone or equivalent per day for greater than two weeks).
• Body mass index (BMI)\>= 40.0 kilogram per square meter.
• The subject has a serious underlying disease that could be imminently life-threatening, or 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: the subject has poorly controlled asthma or chronic obstructive pulmonary disease at baseline, and, in the opinion, of the investigator is not stable on current therapy; the subject has acute severe pain, uncontrolled with conventional medical management; the subject has active peptic ulcer disease; the subject has parkinson's disease; the subject has myasthenia gravis; the subject has history of seizure disorder requiring medications for control. this does not include a history of childhood febrile seizures; the subject has any evidence of mechanical obstruction of the urinary or digestive tracts.
• The subject has had a diagnosis of C. difficile infection (CDI) within 90 days of screening
• The subject has history of seizure disorder requiring medications for control. This does not include a history of childhood febrile seizures.
• The subject is a chronic abuser of alcohol or illicit substances such that it jeopardizes ability to comply with the protocol
• History of sensitivity to any of the study medications, or components thereof or a history of 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 millisecond (msec)
• Corrected QT interval (QTc) \>450msec or QTc \>480msec for subjects with bundle branch block. Note: The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread. The QTc should be based on single or averaged QTc values of triplicate ECGs obtained over a brief recording period. It is essential that the same method for calculating QTc that was used at a subjects baseline visit be used for that subject for all subsequent visits.
• The subject has QRS duration \<70 or \>120 msec.
• The subject has pre-existing grade II atrioventricular block or higher, history of significant vasovagal and/or syncopal episodes, episodes of symptomatic bradycardia.
• The subject has recent acute major blood loss with signs of hemodynamic instability.
• The subject has liver function tests: alanine aminotransferase (ALT) \>2x ULN; alkaline phosphatase and bilirubin \>=1.5xULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (30)

GSK Investigational Site

Phoenix, Arizona, 85021, United States

Location

GSK Investigational Site

Anaheim, California, 92804, United States

Location

GSK Investigational Site

Chula Vista, California, 91942, United States

Location

GSK Investigational Site

La Mesa, California, 91942, United States

Location

GSK Investigational Site

Oceanside, California, 92056, United States

Location

GSK Investigational Site

Sylmar, California, 91342, United States

Location

GSK Investigational Site

Torrance, California, 90502, United States

Location

GSK Investigational Site

Miramar, Florida, 33027, United States

Location

GSK Investigational Site

West Palm Beach, Florida, 33401, United States

Location

GSK Investigational Site

Augusta, Georgia, 30909, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Council Bluffs, Iowa, 51503, United States

Location

GSK Investigational Site

Hazard, Kentucky, 41701, United States

Location

GSK Investigational Site

Zachary, Louisiana, 70791, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55422, United States

Location

GSK Investigational Site

Carriere, Mississippi, 39426, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39216-4505, United States

Location

GSK Investigational Site

Butte, Montana, 59701, United States

Location

GSK Investigational Site

Lincoln, Nebraska, 68510, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 92120, United States

Location

GSK Investigational Site

Belleville, New Jersey, 07109, United States

Location

GSK Investigational Site

Neptune City, New Jersey, 07753, United States

Location

GSK Investigational Site

Albany, New York, 12208, United States

Location

GSK Investigational Site

Brooklyn, New York, 11215, United States

Location

GSK Investigational Site

Lima, Ohio, 45801, United States

Location

GSK Investigational Site

Toledo, Ohio, 43608, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15212, United States

Location

GSK Investigational Site

Channelview, Texas, 77530, United States

Location

GSK Investigational Site

Houston, Texas, 77024, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Scangarella-Oman NE, Ingraham KA, Tiffany CA, Tomsho L, Van Horn SF, Mayhew DN, Perry CR, Ashton TC, Dumont EF, Huang J, Brown JR, Miller LA. In Vitro Activity and Microbiological Efficacy of Gepotidacin from a Phase 2, Randomized, Multicenter, Dose-Ranging Study in Patients with Acute Bacterial Skin and Skin Structure Infections. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01302-19. doi: 10.1128/AAC.01302-19. Print 2020 Feb 21.

  PMID: 31818823 DERIVED

• O'Riordan W, Tiffany C, Scangarella-Oman N, Perry C, Hossain M, Ashton T, Dumont E. Efficacy, Safety, and Tolerability of Gepotidacin (GSK2140944) in the Treatment of Patients with Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections. Antimicrob Agents Chemother. 2017 May 24;61(6):e02095-16. doi: 10.1128/AAC.02095-16. Print 2017 Jun.

  PMID: 28373199 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Bacterial Infections; Infections

Interventions

gepotidacin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: January 27, 2014
• Study Start: March 24, 2014
• Primary Completion: June 29, 2015
• Study Completion: June 29, 2015
• Last Updated: November 17, 2017
• Results First Posted: September 21, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (30)