Last updated: 11/07/2018 04:48:04
A repeat dose study to investigate the interaction of GSK2190915 on the pharmacokinetics of rosuvastatin
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: An open label, sequential, single cohort, repeat dose study to investigate the potential interaction of GSK2190915 on the pharmacokinetics of rosuvastatin in healthy adult subjects.
Trial description: Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli. GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5 lipoxygenase (5-LO) activation. GSK2190915 has been shown to be an in vitro inhibitor of human organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3), hence there is a potential for a pharmacokinetic drug-drug interaction with OATP1/ B1 substrates such as the anti-lipidemic rosuvastatin. This study will evaluate the effect of repeat oral dosing of GSK2190915 (30milligram (mg) and 100mg) on the steady-state pharmacokinetics (PK) of rosuvastatin (10 mg). In addition, the study will evaluate the safety and tolerability of this combination when co-administered to healthy, adult volunteers in two cohorts.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Maximum Concentration (Cmax) of rosuvastatin
Timeframe: On 7 and 14 days post- first dose
Area Under the Curve(0-τ) of rosuvastatin
Timeframe: On 7 and 14 days post first dose
Secondary outcomes:
Safety and tolerability as assessed by clinical monitoring of blood pressure, pulse rate, ECG monitoring and laboratory safety data, as well as reporting of Adverse Events in healthy adult subjects from dosing to one week post-dose.
Timeframe: From screening to follow-up visit
Interventions:
Enrollment:
28
Primary completion date:
Not applicable
Observational study model:
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)
January 2011 to February 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- The subject is of non-Asian origin.
- Aspartate aminotransferase (AST), Alanine aminotransferase (AMT), alkaline phosphatase and bilirubin <1.5xULN (upper limit of normal) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- 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
Inclusion and exclusion criteria
Inclusion criteria:
- The subject is of non-Asian origin.
- Aspartate aminotransferase (AST), Alanine aminotransferase (AMT), alkaline phosphatase and bilirubin <1.5xULN (upper limit of normal) (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 and laboratory tests. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the Investigator believes that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The GSK medical monitor will be consulted where necessary.
- A female subject is eligible to participate if she is 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 Milli lnternational Units/millilitre ( MIU/ml) and estradiol < 40 picogram/ml (pg/ml) (<147 picomoles/Litre (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 8.1 or the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal 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.
- Body weight ≥ 50 kilograms (kg) (110 lbs) for men and ≥ 45 kg (99lbs) for women and BMI (body mass index) within the range 18-30 kg/m2 inclusive.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- 12 lead ECG (electrocardiogram) without any clinically significant abnormality as judged by the Investigator, and average QTc (corrected QT duration), QTcB or QTcF < 450 msec
Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Exclusion criteria:
- 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
- Current, or history of, muscle complaints (e.g. unexplained weakness, tenderness, pain), myopathy or rhabdomyolysis.
- Current, or history of, renal impairment or insufficiency.
- Current, or history of, hypothyroidism.
- Lactose intolerant, including galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- A positive pre-study drug/alcohol screen.
- A positive test for HIV (Human Immunodeficiency Virus) antibody.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >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.
- 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: 90 days, 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.
- 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 90 day period.
- Pregnant females as determined by positive serum hCG (Human chorionic gonadotrophin) test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Urinary cotinine levels or breath 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 or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
Trial location(s)
Location
GSK Investigational Site
London, United Kingdom, NW10 7EW
Status
Terminated/Withdrawn
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
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-23-02
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 112362 can be found on the GSK Clinical Study Register.
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