GSK2190915 Neutrophilic Asthma Study

NCT01471665 | Completed Phase 2

• 1 other identifier: 115134
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effect on repeat doses of GSK2190915 in asthmatic patients with a high percentage of neutrophils in their sputum. GSK2190915 will be given as an add on to current therapy, and its effects on the percentage of sputum neutrophils in the patients will be assessed.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• The numbers of neutrophils in induced sputum in asthmatic subjects (average of absolute and percentage count on Visit 4 and Visit 5)

  Pharmacodynamics

  13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily

Secondary Outcomes (7)

• The levels of LTE4 in urine, LTB4-glucuronide in urine and LTB4 in sputum supernatant in asthmatic subjects

  Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily

• The levels of high sensitive C-reactive protein (hsCRP) and other biomarkers (for example IL-17) in blood in asthmatic subjects

  Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily

• Changes in symptoms in asthmatic subjects compared to placebo using the asthma control questionnaire

  Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily

• Changes in lung function as measured by Forced Expiratory Volume in one second (FEV1) in subjects with asthma

  Over 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily

• Plasma concentrations of GSK2190915 following repeated doses in asthmatic subjects

  On days 13 - 16 days post treatment with 100mg GSK2190915 or placebo once daily

Study Arms (2)

GSK2190915 100mg

EXPERIMENTAL

This is a crossover study so patients will receive 100mg of GSK2190915 once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the placebo arm of the study.

Drug: GSK2190915 100mg

Placebo

PLACEBO COMPARATOR

This is a crossover study so patients will receive placebo once daily for up to 16 days followed by a wash out period of at least 14 days before they cross over onto the GSK2190915 100mg arm of the study.

Drug: Placebo

Interventions

GSK2190915 100mg DRUG

GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor. Dosing will occur once daily for up to 16 days.

GSK2190915 100mg

Placebo DRUG

Placebo will be administered once daily for up to 16 days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \< 2xUpper limit of normal (ULN); alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Males and females ages 18 years old and above.
• An established clinical history of asthma in accordance with the definition by the GINA Guidelines.
• Subjects who are stable on their current treatment for at least one month prior to first dose and for the duration of the study.
• Persistent sputum neutrophilia in the absence of infection. Persistent is defined at being met at Screening and Visit 1 of Treatment Period 1. At least one sputum sample must show neutrophils ≥ 50%. The other sample must be \> 45%.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented (medical report verification) hysterectomy or double oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels \> 40 mIU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods specified in the protocol if they wish to continue their Hormone Replacement Therapy (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.
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 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 the follow up visit, or at least 6 days after last dose.
• Signed and dated written informed consent is obtained from the subject
• The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• The subject has tested positive for Human Immunodeficiency Virus ev1(HIV) antibodies.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (excluding asthma but including but not confined to chronic bronchitis, emphysema, bronchiectasis, eosinophilic bronchitis or pulmonary fibrosis).
• History of asthma exacerbations or acute intercurrent respiratory illness (viral respiratory syndrome, bronchitis, pneumonia) for a four week period before the screening visit.
• History of life-threatening asthma, defined as an asthma episode that required intubations and/or was associated with hypercapnia, respiratory arrest and/or hypoxic seizures.
• FEV1 \< 1 litre post salbutamol.
• Clinically significant abnormalities in vital signs or safety laboratory analysis at screening.
• The subject has a clinically significant QT duration corrected for heart rate (QTc) value at screening.
• The subject has a positive pre-study urine drug or urine or breath alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
• Administration of injectable steroids within 6 weeks of screening.
• Administration of any vaccinations within 2 weeks of screening or during the study.
• Administration of biological therapies within 3 months of the screening visit or during the study.
• Subject is undergoing allergen desensitisation therapy.
• Administration of OATP1B1 substrates from 2 weeks before dosing, and until all follow up assessments are completed.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

Related Publications (1)

• Chaudhuri R, Norris V, Kelly K, Zhu CQ, Ambery C, Lafferty J, Cameron E, Thomson NC. Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum neutrophils. Pulm Pharmacol Ther. 2014 Feb;27(1):62-9. doi: 10.1016/j.pupt.2013.11.007. Epub 2013 Dec 10.

  PMID: 24333186 DERIVED

Related Links

• 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

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: November 16, 2011
• Study Start: June 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: November 22, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)