A Repeat Dose Study to Investigate the Interaction of GSK2190915 on the Pharmacokinetics of Rosuvastatin

NCT01411111 | Completed Phase 1

• 1 other identifier: 112362
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma

Keywords

Drug-drug interaction; rosuvastatin; asthma; FLAP inhibitor

Outcome Measures

Primary Outcomes (2)

• Maximum Concentration (Cmax) of rosuvastatin

  On 7 and 14 days post- first dose

• Area Under the Curve(0-τ) of rosuvastatin

  On 7 and 14 days post first dose

Secondary Outcomes (1)

• 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.

  From screening to follow-up visit

Study Arms (2)

Rosuvastatin foll by GSK2190915 30mg + rosuvastatin

ACTIVE COMPARATOR

Subjects will be orally administered rosuvastatin 10 mg/day for 7 days in treatment period 1. The subjects will then receive rosuvastatin 10 mg/day in combination with GSK2190915 30 mg/day for 7 days in treatment period 2A.

Drug: Rosuvastatin 10 mg; Drug: GSK2190915 30mg

Rosuvastatin foll by GSK2190915 100mg + rosuvastatin

ACTIVE COMPARATOR

Subjects will be orally administered rosuvastatin 10 mg/day for 7 days in treatment period 1. The subjects will then receive rosuvastatin 10 mg/day in combination with GSK2190915 100 mg/day for 7 days in treatment period 2B.

Drug: Rosuvastatin 10 mg; Drug: GSK2190915 100mg

Interventions

Rosuvastatin 10 mg DRUG

days 1-14

Rosuvastatin foll by GSK2190915 100mg + rosuvastatin; Rosuvastatin foll by GSK2190915 30mg + rosuvastatin

GSK2190915 30mg DRUG

1x30mg tablet, days 8-14

Rosuvastatin foll by GSK2190915 30mg + rosuvastatin

GSK2190915 100mg DRUG

1x100mg tablet, days 8-14

Rosuvastatin foll by GSK2190915 100mg + rosuvastatin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• 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.
• lead ECG (electrocardiogram) without any clinically significant abnormality as judged by the Investigator, and average QTc (corrected QT duration), QTcB or QTcF \< 450 msec

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

Related Links

• Results for study 112362 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Asthma

Interventions

Rosuvastatin Calcium; 3-(3-tert-butylsulfanyl-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropionic acid

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2011
• First Posted: August 8, 2011
• Study Start: January 6, 2011
• Primary Completion: February 23, 2011
• Study Completion: February 23, 2011
• Last Updated: July 25, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)