Last updated: 11/07/2018 07:58:49
A single oral escalating dose study of GSK2140944 in healthy volunteers
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Randomized, Single Blind, Placebo Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of GSK2140944 in Healthy Adult Subjects
Trial description: GSK2140944 belongs to the Bacterial Type II Topoisomerase Inhibitor (BTI) class of antibiotics. GSK2140944 has demonstrated in vitro and in vivo activity against Gram positive including methicillin resistant Staphylococcus aureus (MRSA) and Gram-negative pathogens associated with respiratory tract, skin and soft tissue infections including isolates resistant to existing classes of antimicrobials. This is a First Time in Human (FTIH) study to assess the safety, tolerability, and pharmacokinetics of single oral doses of GSK2140944 in healthy volunteers. This study will be a single-blind, randomized, placebo-controlled, dose-rising study in healthy subjects. The proposed single doses will range from 100 mg to 3000 mg.
Primary purpose:
Other
Trial design:
Parallel Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
GSK2140944 clinical safety data assessed as change from baseline in 12-lead ECG
Timeframe: Day 1, Day 2, Day 3 and at the Follow-up visit
GSK2140944 clinical safety data from dual-lead cardiac monitoring
Timeframe: Day -1, Day 1
GSK2140944 clinical safety data assessed as change from baseline in clinical laboratory tests
Timeframe: Day -1, Day 2, Day 3 and the Follow-up visit
GSK2140944 clinical safety data assessed as by number of adverse events (AE)
Timeframe: Up to the Follow-up visit
GSK2140944 clinical safety data assessed as change from baseline in blood pressure
Timeframe: Day -1, Day 1, Day 2, Day 3 and the Follow-up visit
GSK2140944 clinical safety data assessed as change from baseline in heart rate
Timeframe: Day -1, Day 1, Day 2, Day 3 and the Follow-up visit
Secondary outcomes:
Pharmacokinetic parameter: AUC(0-t) following single dose of GSK2140944
Timeframe: Up to Day 4
Pharmacokinetic parameter: AUC(0-infinity) following single dose of GSK2140944
Timeframe: Up to Day 4
Pharmacokinetic parameter: Cmax following single dose of GSK2140944
Timeframe: Up to Day 4
Pharmacokinetic parameter: tmax following single dose of GSK2140944
Timeframe: Up to Day 4
Pharmacokinetic parameter: t1/2 following single dose of GSK2140944
Timeframe: Up to Day 4
To assess preliminary dose proportionality using PK parameter AUC(0-infinity) following single dose of GSK2140944
Timeframe: Up to Day 4
To assess preliminary dose proportionality using PK parameter Cmax following single dose of GSK2140944
Timeframe: Up to Day 4
Pharmacokinetic parameter: (Ae) following single dose of GSK2140944
Timeframe: Up to Day 4
Pharmacokinetic parameter: (CLr) following single dose of GSK2140944
Timeframe: Up to Day 4
Interventions:
Enrollment:
48
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Infections, Respiratory Tract
Product
gepotidacin
Collaborators
Not applicable
Study date(s)
September 2011 to February 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 60 years
Accepts healthy volunteers
Yes
- AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- 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.
- Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
- A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening.
Inclusion and exclusion criteria
Inclusion criteria:
- AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- 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.
- Male or female ranging from 18 to 60 years of age, at the time of signing the informed consent. Female subject must be 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]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Body weight ≥ 50 kg and BMI within the range 19
- 31 kg/m2, inclusive.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- QTcF < 450 msec, or QTc < 480 msec in subjects with Bundle Branch Block., at screening.
Exclusion criteria:
- Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the subject at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
- A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening.
- A screening urinalysis positive for protein or glucose (greater than “trace” findings of protein or glucose).
- Positive for Human Immunodeficiency Virus (HIV) antibody, hepatitis B virus surface antigen, or hepatitis C virus antibody at screening.
- History of drug abuse within 6 months of the study.
- History of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
- History of regular alcohol consumption exceeding an average weekly intake of greater than or equal to 21 units for men/14 units for women or an average daily intake of greater than or equal to 3 units for men/2 units for women. One unit is equivalent to a 285 mL glass of full strength beer or 425 mL schooner of light beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine.
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Use of prescription or non-prescription drugs, including vitamins above the recommended daily intake (National Health and Medical Research Council in Australia guideline), herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John’s Wort within 14 days prior to the first dose of study medication. By exception, the volunteer may take paracetamol or acetaminophen (≤ 2 grams/day) or ibuprofen (1600 mg/day) up to 48 hours prior to the first dose of study medication. However, the investigator and study team can review medication use on a case by case basis to determine if its use would compromise subject safety or interfere with study procedures or data interpretation.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits or grapefruit hybrids or fruit juices containing such products for 7 days prior to administration of study medication.
- Donation of blood in excess of 550 mL within 12 weeks prior to dosing.
- An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women, or an unwillingness of male subjects to use a condom and spermicide, in addition to having their female partner use another form of contraception such as an IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or a tubal ligation, if engaging in sexual intercourse with a female partner who could become pregnant. This criterion must be followed from the time of study medication administration and until 84 days after study medication administration.
- 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 physician responsible, contraindicates their participation.
- History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
- An unwillingness to comply with lifestyle and/or dietary restrictions as described in Section 8.
Trial location(s)
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2012-15-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 114595 can be found on the GSK Clinical Study Register.
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