Last updated: 11/28/2018 09:50:27
Blood levels and effects of GSK1325756 in healthy adult volunteers aged 40 to 80 years old
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomized cross-over study to evaluate the pharmacokinetics and pharmacodynamics of twice daily oral administration of GSK1325756, compared to placebo, in healthy subjects; and the pharmacokinetic profile of twice daily oral administration of GSK1325756 in healthy fed and fasted elderly subjects
Trial description: This study will invite two groups of volunteers to participate.The data from one group of volunteers will be used to find out how much study drug, known as GSK1325756, is in the blood after taking the drug twice in one day. Data will also collected to find out if the level of cetain blood cells, known as neutrophils, change significantly after taking the study drug twice in one day. This group of volunteers will be aged 40 to 64 years of age.The data from the other group of volunteers will be used to find out if taking the study drug, GSK1325756, twice in one day with or without food, makes a difference to the level of study drug in the blood. This group of volunteers will also provide data to find out if any study drug metabolites are present in the bile, a fluid secreted by the liver. This group of volunteers will be aged 65 to 80 years of age.
Primary purpose:
Basic Science
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Pharmacokinetics
Timeframe: 48 hours
Secondary outcomes:
Pharmacodynamics
Timeframe: 48 hours
Adverse Events
Timeframe: 48 hours
Interventions:
Enrollment:
40
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Bloomer JC, Nash M, Webb A, Miller B, Lazaar A, Beaumont C, Guiney W. Assessment of potential drug interactions by characterisation of human drug metabolism pathways using non-invasive bile sampling. Br J Clin Pharmacol. 2013;75(2):488-496.
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
danirixin
Collaborators
Not applicable
Study date(s)
November 2010 to January 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
40 - 85 years
Accepts healthy volunteers
Yes
- Male or non-childbearing potential female who, at the at the time of signing the informed consent, aged between 40 and 64 years (inclusive) for enrolment in Part A - Cohort 1; between 65 and 80 years (inclusive) for enrolment in Part B – Cohort 2. A female of non-childbearing potential is defined as a pre-menopausal female 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].
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A neutrophil count at screening of less than 2 x 10*9L. Repeat testing is not permitted.
Inclusion and exclusion criteria
Inclusion criteria:
- Male or non-childbearing potential female who, at the at the time of signing the informed consent, aged between 40 and 64 years (inclusive) for enrolment in Part A
- Cohort 1; between 65 and 80 years (inclusive) for enrolment in Part B – Cohort 2. A female of non-childbearing potential is defined as a pre-menopausal female 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].
- 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 and objectives.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN) (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
- Resting blood pressure (BP) of less than or equal to 140/90, irrespective of anti-hypertensive medication status for the subject.
- Body weight greater or equal to 60 kg for men and greater or equal to 45 kg for women; and Body Mass Index (BMI) within the range 19 to 32 kilograms per metres squared (kg/m2) (inclusive).
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until one week post last dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria:
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A neutrophil count at screening of less than 2 x 10*9L. Repeat testing is not permitted.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen, with the exception of a positive result considered by the investigator to be directly attributable to prescription medication approved for subject use during the study.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males or greater than 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.
- Positive serum or urine human chorionic gonadotropin (hCG) test at screening or prior to first dose.
- Screening QT duration corrected for heart rate by Bazett's formula (QTcB) or QT correction for heart rate by Fridericia's formula (QTcF) greater than 450 msec; PR interval outside the range 120 to 200 msec or an ECG that it not suitable for QT measurements (e.g. poorly defined termination of T-wave).
- 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 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, such as a subject who is taking a stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit; or lipid lowering medications (statins or fibrates) for at least 3 months prior to the screening visit.
- Treatment with intravenous or intra-articular corticosteroids within 6 weeks of first dose of study medication.
- Current treatment with proton pump inhibitors (e.g. omeprazole, lansoprazole).
- Current treatment with H2-receptor antagonists (e.g. ranitidine or cimetidine).
- 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 3-month period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Urinary cotinine or exhaled breath carbon monoxide (CO) 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.
- Direct involvement in the conduct of the study, or relative or any person directly involved in the conduct of the study
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
2011-27-01
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 114922 can be found on the GSK Clinical Study Register.
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