A Single Dose Study to Assess the Regional Absorption and Bioavailability of 100mg GSK2190915A
A Single Dose, Crossover Study in Healthy Female Subjects to Assess the Regional Absorption and Bioavailability of 100 mg GSK2190915A
1 other identifier
interventional
14
1 country
1
Brief Summary
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes through the blockage of the first step in the leukotriene pathway, 5-lipoxygenase (5-LO) activation. GSK2190915 inhibits the production of leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs). This is an open label, 4-way, 4-treatment period, non-randomised, crossover study with an interim analysis. The GSK2190915 formulations used in this study will be: a 100mg and 200mg milled tablet, a 100mg enteric-coated tablet, and a \[14C\] radiolabelled GSK2190915 intravenous solution. This study aims to determine the pharmacokinetics and absolute bioavailability of GSK2190915 to enable optimisation of suitable formulations to be used in clinical development Fourteen subjects will be dosed to ensure data in 10 at the end of the clinical study. Seven of the subjects will receive an IV microtracer in addition to the other treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 asthma
Started Sep 2010
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 30, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 11, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
March 11, 2011
CompletedFirst Submitted
Initial submission to the registry
March 17, 2011
CompletedFirst Posted
Study publicly available on registry
March 21, 2011
CompletedAugust 3, 2017
August 1, 2017
5 months
March 17, 2011
August 1, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Characterisation of the maximum concentration (Cmax), the time of Cmax (tmax) and Area Under the plasma concentration-time Curve (AUC) for intravenous and oral pharmacokinetics
1 month
Determination of AUC data for all routes of administration to permit calculation of relative and absolute bioavailability where appropriate.
1 month
Assessment of regiospecific bioavailability of GSK2190915A based on tmax, Cmax, and AUC to assist in subsequent oral formulation/delivery options for GSK2190915A
1 month
Secondary Outcomes (3)
To collect further information about the safety and tolerability of GSK2190915A by assessing: physical examination, safety laboratory tests, vital signs, electrocardiogram (ECG), adverse events.
1 month
Quantitative and cumulative recovery of radiocarbon in urine and faeces to permit an assessment of deposition route for intravenous GSK2190915A.
1 month
Collection of bile to allow profiling of metabolites of GSK2190915A.
1 month
Study Arms (5)
Period 1 Cohort 1 - GSK2190915 100mg
EXPERIMENTALPeriod 1 - GSK2190915 100mg tablet.
Period 1 Cohort 2 - GSK2190915 100mg plus microtracer
EXPERIMENTALPeriod 1 - GSK2190915 100mg tablet plus \[14C\] radiolabelled GSK2190915 microtracer solution.
Period 2 GSK2190915 100mg to proximal small bowel
EXPERIMENTAL100mg of ground half 200mg GSK2190915 tablet administered to the proximal small bowel via Enterion capsule.
Period 3 GSK2190915 100 mg to distal small bowel
EXPERIMENTAL100mg of ground half 200mg GSK2190915 tablet administered to the distal small bowel via Enterion capsule.
Period 4 - GSK 100mg enteric-coated tablet
EXPERIMENTAL100mg enteric-coated GSK2190915 coated tablet.
Interventions
Taken orally
Microtracer solution
Ground half of a 200mg tablet. Administered via Enterion capsule.
Ground half of a 200mg tablet. Administered via Enterion capsule.
Eligibility Criteria
You may qualify if:
- Healthy females as determined by an experienced study physician, based on a medical evaluation including medical history, physical examination, neurological 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;
- Females must be either:
- 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. \[Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 9.4 of the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.\]
- Of child-bearing potential and agrees to use one of the contraception methods listed in Section 9.4 of the protocol for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 3 months after the last dose.
- Aged 18-65 years;
- Body Mass Index (BMI) of 18-35 kilogram per sqare metre (km/m2);
- Subjects must demonstrate their ability to swallow an empty size 000 capsule;
- Must be willing and able to participate in the whole study and must provide written informed consent;
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5xUpper Limit of Normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%);
- QTcB or QTcF \< 450 msec
- Subjects of child-bearing potential must agree to use one of the contraception methods listed in Section 9.4 from the time of the first dose of study medication until 3 months following the last dose.
You may not qualify if:
- Participation in a clinical research study involving investigational drugs or dosage forms within the previous 3 months or 4 months if new chemical entity (NCE);
- Subjects who have previously been enrolled in this study;
- Subjects who have ever sought advice from or been referred to a General Practitioner or counsellor for abuse or misuse of alcohol, non medical drugs, medicinal drugs or other substance abuse e.g. solvents;
- Subjects who admit to any current or previous use of Class A drugs such as opiates, cocaine, ecstasy, lysergic acid diethylamide (LSD) and intravenous amphetamines (Subjects who admit to occasional past use of cannabis will not be excluded as long as they have a negative drugs of abuse test and have been abstinent for at least 12 months;)
- Positive drugs of abuse test result;
- Regular alcohol consumption \>14 units per week (1 Unit = ½ pint beer, a 25 milliLitre (mL) shot of 40% spirit or a 125 mL glass of wine);
- 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 Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening;
- Radiation exposure from clinical trials, including that from the present study, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 milliSieverts (mSv) in the last twelve months or 10 mSv in the last five years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 1999, shall participate in the study;
- Subjects must not have had any 14C exposure within the last 12 months.
- Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the Principal Investigator (PI);
- History of gastrointestinal surgery (with the exception of appendectomy unless it was performed within the previous 12 months);
- History of clinically significant cardiovascular, renal, hepatic, respiratory and particularly gastrointestinal disease, especially peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome;
- History of adverse reaction or allergy to study drug or its excipients, e.g. lactose or rescue medication (if specified by the Sponsor);
- If subject suffers from hayfever they must not have or be expecting to have symptoms during the study period;
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (1)
GSK Investigational Site
Nottingham, NG11 6JS, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 17, 2011
First Posted
March 21, 2011
Study Start
September 30, 2010
Primary Completion
March 11, 2011
Study Completion
March 11, 2011
Last Updated
August 3, 2017
Record last verified: 2017-08
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.