Last updated: 11/07/2018 07:59:04
A single dose study to assess the regional absorption and bioavailability of 100mg GSK2190915A
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A single dose, crossover study in healthy female subjects to assess the regional absorption and bioavailability of 100 mg GSK2190915A
Trial description: 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 developmentFourteen 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.
Primary purpose:
Basic Science
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
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
Timeframe: 1 month
Determination of AUC data for all routes of administration to permit calculation of relative and absolute bioavailability where appropriate.
Timeframe: 1 month
Assessment of regiospecific bioavailability of GSK2190915A based on tmax, Cmax, and AUC to assist in subsequent oral formulation/delivery options for GSK2190915A
Timeframe: 1 month
Secondary outcomes:
To collect further information about the safety and tolerability of GSK2190915A by assessing: physical examination, safety laboratory tests, vital signs, electrocardiogram (ECG), adverse events.
Timeframe: 1 month
Quantitative and cumulative recovery of radiocarbon in urine and faeces to permit an assessment of deposition route for intravenous GSK2190915A.
Timeframe: 1 month
Collection of bile to allow profiling of metabolites of GSK2190915A.
Timeframe: 1 month
Interventions:
Drug: GSK2190915 100mg milled tablet
Drug: [14C] radiolabelled GSK2190915 solution
Drug: GSK2190915 100mg milled tablet administered to the proximal small bowel.
Drug: GSK2190915 100mg milled tablet administered to the distal small bowel.
Drug: GSK2190915 100mg enteric-coated tablet.
Enrollment:
14
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Daley-Yates P, Norris G, Ambry C, Preece A. An open-label, randomised, single-dose, multi-cohort, crossover bioavailability study of a solution formulation and three capsule formulations of GSK2190915 in healthy adult subjects followed by a repeat-dose, randomized, parallel group, double-blinded. British Pharmacological Society - 2012 Winter Meeting. 2012
Medical condition
Asthma
Product
fiboflapon
Collaborators
Not applicable
Study date(s)
September 2010 to March 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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:
- 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;
Inclusion and exclusion criteria
Inclusion criteria:
- 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. -
Exclusion criteria:
- 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;
- Acute diarrhoea or constipation in the 7 days before the predicted first study day. If screening occurs >7 days before the first study day, this criterion will be determined on first study day. Diarrhoea will be defined as the passage of liquid faeces and/or a stool frequency of greater than three times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day;
- Donation, or significant loss as judged by the investigator, of blood within the previous three months;
- Presence of non-removable metal objects such as metal plates, screws, etc, in the abdominal region of the body (with the exception of sterilisation clips);
- Subjects will be excluded from the study if they are considered by the PI to be at risk of transmitting, through blood or other body fluids, the agents responsible for acquired immunodeficiency syndrome (AIDS) or other sexually transmitted disease or hepatitis;
- Positive Hepatitis B Virus, Hepatitis C Virus or Human Immunodeficiency Virus (HIV)results;
- Unwillingness or inability to follow the procedures outlined in the protocol;
- Subject is mentally or legally incapacitated;
- Failure to satisfy the PI of fitness to participate for any other reason.
Trial location(s)
Location
GSK Investigational Site
Nottingham, United Kingdom, NG11 6JS
Status
Will Be Recruiting
Study documents
Clinical study report
Available language(s): English
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
Completed
Actual primary completion date
Not applicable
Actual study completion date
2011-11-03
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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