Last updated: 11/28/2018 10:00:59
A study to look at how GSK1325756 is taken up by the body when given by mouth when stomach acid is reduced
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Single Centre, 5-Period, Randomized Study To Evaluate The Relative Bioavailability Of An Immediate Release Tablet Formulation And Prototype Bioenhanced Formulations Of GSK1325756 In Healthy Elderly Subjects During Suppression Of Gastric Acid Secretion
Trial description: This is a Phase I study to assess the combined effects of food and suppression of gastric acid secretion on the relative bioavailability of an immediate release (IR) tablet formulation and prototype bioenhanced formulations of GSK1325756, an oral interleukin 8 receptor (IL8R also known as CXCR2) antagonist. The objectives are to understand if the co-administration of food enhances absorption and the inter-subject variability for the current GSK1325756 IR tablet under fed state proton pump inhibitor (PPI) conditions and secondly to assess whether two proposed bioenhanced formulations offer any improvement over the current GSK1325756 IR formulation under PPI conditions.This open-label, randomized, 5-period crossover study will be completed in a single cohort of subjects, with an interim analysis after completion of Treatment Period 4. During Treatment Periods 1 to 4, subjects will be randomized to receive GSK1325756 50 mg IR in the fed state, GSK1325756 50 mg IR in the fasted state, GSK1325756 Bioenhanced Formulation 1 in the fasted state, and GSK1325756 Bioenhanced Formulation 2 in the fasted state. Progression to Treatment Period 5 and the choice of bioenhanced formulation for dosing in this treatment period will be dependent on the findings of an interim analysis of the pharmacokinetic profile and relative bioavailability of each formulation following completion of Treatment Periods 1 to 4. In Treatment Period 5, subjects will receive the selected GSK1325756 bioenhanced formulation in the fed state.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Pharmacokinetics
Timeframe: Forty eight hour period following dose
Secondary outcomes:
Pharmacokinetics
Timeframe: Forty eight hour period following dose
Safety and tolerability information
Timeframe: Study Duration
Interventions:
Enrollment:
20
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
B. E. Miller, K. Smart, S. Mistry, C. Ambery, J. C. Bloomer, P. Connolly, D. Sanderson, T. Shreeves, R. Smith, A. L. Lazaar.The pharmacokinetics of conventional and bioenhanced tablet formulations of danirixin (GSK1325756) following oral administration in healthy, elderly, human volunteers.Eur J Drug Metab Pharmacokinet.2014;39(3):173-181
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
danirixin
Collaborators
Not applicable
Study date(s)
October 2011 to December 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
65 - 80 years
Accepts healthy volunteers
Yes
- Male or non-childbearing potential female who, at the time of signing the informed consent, are aged between 65 and 80 years (inclusive). Non-childbearing potential is 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] greater than 40 milli-international units per milliliter MlU/mL) and estradiol less than 40 picograms per milliliter (pg/mL) [less than 147 picomoles per liter (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 GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives.
- 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 Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody (HCV Ab) result within 3 months of screening.
Inclusion and exclusion criteria
Inclusion criteria:
- Male or non-childbearing potential female who, at the time of signing the informed consent, are aged between 65 and 80 years (inclusive). Non-childbearing potential is 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] greater than 40 milli-international units per milliliter MlU/mL) and estradiol less than 40 picograms per milliliter (pg/mL) [less than 147 picomoles per liter (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 GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives.
- Aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) (isolated bilirubin greater than 1.5 times the ULN is acceptable if bilirubin is fractionated and direct bilirubin is less than 35 percent (%)).
- Resting blood pressure of less than or equal to 160/95 millimeters of mercury (mm Hg), irrespective of anti-hypertensive medication status for the subject.
- Body weight greater than or equal to 60 kilograms (kg) for men and greater than or equal to 45 kg for women; body mass index within the range 19 to 32 kiligrams per meter squared (kg/m2) (inclusive).
- Male subjects with female partners of child-bearing potential must agree to use two of the following acceptable forms of contraception methods, one of which must be a barrier method, from screening until 12 weeks after the last dose of study treatment: 1) Established use of oral, injected or implanted methods of contraception. (The decision to allow use of hormonal contraceptives should be based on the investigational medicinal product’s metabolism and potential for interactions, pharmacology and adverse event profile e.g., vomiting) 2) Placement of an intrauterine device or system 3) Barrier method such as a condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. Barrier contraceptives must always be supplemented with the use of a spermicide, which are not a barrier method and therefore should not be used alone 4) Male sterilization 5) True abstinence is acceptable when in line with the preferred and usual lifestyle of the subject. If a subject is not usually sexually active but becomes active, they should, with their partner, use two of the contraceptive methods listed above.
- 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 positive pre-study Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody (HCV Ab) 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 human immunodeficiency virus (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 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Positive urine beta-human chorionic gonadotropin (β-hCG) test at screening or prior to first dose for female subjects.
- Screening QT interval analysed by Bazett correction (QTcB) greater than 450 msec, PR interval outside the range 120 to 220 msec or an ECG that is 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 treatment until completion of the post-study medical, unless in the opinion of the investigator and GlaxoSmithKline (GSK) Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety; examples are anti-hypertensive medication for at least 3 months prior to the screening visit and lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit.
- History of sensitivity to any of the study treatments, 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 milliliters (mL) within a 3-month period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Exhaled breath carbon monoxide levels indicative of smoking (greater than 10 parts per million at screening), 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, citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study treatment until collection of the final blood sample during each treatment period.
- Galactose intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
- Direct involvement in the conduct of the study, or relative of 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
2011-19-12
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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