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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01262885
Other study ID # 114470
Secondary ID
Status Completed
Phase Phase 1
First received December 16, 2010
Last updated June 27, 2017
Start date October 7, 2010
Est. completion date August 25, 2011

Study information

Verified date June 2017
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

GSK2251052 ((S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride) is a Gram negative antibacterial compound currently in development for the treatment of hospital acquired Gram negative infection (including E. coli, K. pneumoniae, and Enterobacter spp.) This study will be conducted in two (2) parts, with single oral doses being explored in Part A (500, 1000, and 2000 mg) and repeat oral doses (1000 and 2000 mg, b.i.d.) being explored in Part B. Parts A and B will be single-blind, randomized, placebo-controlled, dose-rising studies in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of oral GSK2251052.


Recruitment information / eligibility

Status Completed
Enrollment 84
Est. completion date August 25, 2011
Est. primary completion date August 25, 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria:

- AST, ALT, alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

- Abnormal LFT tests may be repeated once at the discretion of the Investigator. If an abnormality is repeated, the subject would not be eligible for inclusion.

- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with coagulation, reticulocyte, or Hgb values outside the normal range should always be excluded from enrollment.

- Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.

- A female subject is eligible to participate if she is of:

- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory].

- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until at least 90 days post-last dose.

- Body weight > 50 kg and BMI within the range 19 - 32 kg/m2 (inclusive).

- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

- QTc, QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.

- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

- 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 GSK Medical Monitor, contraindicates their participation.

- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.

- Lactating females.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Subject is mentally or legally incapacitated.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Subjects who have asthma or a history of asthma, (e.g., for any FTIH where risk of bronchoconstriction is unknown, or compound specific where risk of bronchoconstriction).

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.

- A history of orthostatic hypotension

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
GSK2251052
500 mg tablet, dose levels detailed in Arm description
Placebo
matching placebo tablet

Locations

Country Name City State
Australia GSK Investigational Site Adelaide South Australia

Sponsors (1)

Lead Sponsor Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Australia, 

Outcome

Type Measure Description Time frame Safety issue
Primary Adverse event reporting, clinical laboratory tests, vital signs, cardiac monitoring, urinalysis, and clinical monitoring/observation. within 35 days of first dose
Primary Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, t1/2, Ae, fe, and CLr of GSK2251052 as data permit. within 14 days of first dose
Secondary AUC(0-t), AUC(0-inf), and Cmax following single dose administration for the assessment of dose proportionality within 72 h of dosing
Secondary Trough plasma concentrations within 10 days of first dose
Secondary Accumulation based on AUC(Ro) and Cmax (RCmax) and determine the steady-state ratio (Rss) within 14 days of first dose
Secondary AUC(0-t)am and Cmax,am following repeat administration at different doses for the assessment of dose proportionality within 14 days of first dose
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