Last updated: 11/27/2018 17:00:41
First Time in Human Study with GSK1325756
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A single-centre, double-blind, placebo-controlled study to evaluate the safety, tolerabilty, pharmacokinetics, and pharmacodynamics of single, oral, ascending doses and repeat oral doses of GSK1325756 in healthy male subjects.
Trial description: This study aims to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single, oral ascending doses, and repeat oral doses of GSK1325756 administered to healthy adult male volunteers. This study is the First Time in Human study for GSK1325756.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Safety and tolerabilty of GSK1325756 as assessed by clinical monitoring of blood pressure, pulse rate, ECG, and laboratory data, as well as reporting of AEs.
Timeframe: Study duration
Secondary outcomes:
Area under the blood concentration-time curve, Maximum Concentration (Cmax), Time to Cmax (Tmax), terminal half-life and oral clearance of GSK1325756 following the administration of single escalating oral doses of GSK1325756 in healthy adult subjects.
Timeframe: Study duration
Area under the blood drug concentration-time curve, trough 24-hour Concentration (C24), Cmax, Tmax and accumulation of GSK1325756 following the administration of once daily repeat doses of two selected doses of GSK1325756 for 14 days in healthy subjects.
Timeframe: Study duration
Flow cytometric quantification of CXCL1-induced CD11b cell surface expression on peripheral blood neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
Timeframe: Study duration
PK-PD model of the relationship between the blood concentration of GSK1325756 and CXCL1-induced CD11b cell surface expression on neutrophils ex vivo following the administration of single and repeat oral doses of GSK1325756 in healthy adult subjects
Timeframe: Study duration
Interventions:
Enrollment:
58
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Bruce E. Miller, Sunil Mistry, Kevin Smart, Paul Connolly, Donald C. Carpenter5, Hiran Cooray, Jackie C. Bloomer, Ruth Tal-Singer and Aili L. Lazaar.The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756) ? a selective CXCR2 antagonist ? in healthy adult subjects.BMC Pharmacol Toxicol.2015;16(18)
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
danirixin
Collaborators
Not applicable
Study date(s)
October 2009 to March 2010
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (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 Electrocardiogram (ECG). 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.
- Cotinine or Exhaled Breath Carbon Monoxide (CO) Test indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A neutrophil count at screening of < 2 x 10(9) per litre (/L)
Inclusion and exclusion criteria
Inclusion criteria:
- Aspartate Transaminase (AST), Alanine Transaminase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN) (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 Electrocardiogram (ECG). 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.
- Males between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Condom (during non-vaginal intercourse with any partner
- Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female) This criterion must be followed from the time of the first dose of study medication until at least 3-months post-last dose of study drug.
- Body weight ≥ 60 kilograms (kg) and Body Mass Index (BMI) within the range 19 – 31 kilogrammes per square metre (kg/m-2) (inclusive)
- 12-lead ECG without any clinically significant abnormality as judged by the Investigator, and average QTcB or QTcF (ECG paramaters) < 450 msec
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Able to complete all study procedures and planned treatment periods.
Subjects must agree to use one of the contraception methods listed below: To prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject’s semen, male subjects must use one of the following contraceptive methods:
male or female) OR
Exclusion criteria:
- Cotinine or Exhaled Breath Carbon Monoxide (CO) Test indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A neutrophil count at screening of < 2 x 10(9) per litre (/L)
- 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).
- Significant cardiac, pulmonary, metabolic, renal, gastrointestinal or other conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial
- 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. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliLitres(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: 3 months, 5 half-lives or twice the duration of the expected 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) or 5 half-lives (whichever is longer) 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. Prescription and non-prescription non-steroidal anti-inflammatory drugs are not permitted.
- 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.
- Subject is mentally or legally incapacitated.
- 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.
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
Clinical study report
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
2010-02-03
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.
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