GSK2190915 Moderate to Severe Asthma Study

NCT00850642 | Terminated Phase 2 Results

• 2 other identifiers: 1120462008-007244-33
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 8

Brief Summary

A randomised, double-blind, placebo-controlled, parallel group study to evaluate the effect of treatment with GSK2190915, a FLAP inhibitor, as add-on to current inhaled corticosteroid therapy in patients with moderate to severe asthma with elevated sputum neutrophils.

Conditions

Asthma

Keywords

Sputum cell counts; Neutrophils; Severe Asthma; ICS; Inhaled corticosteroids

Outcome Measures

Primary Outcomes (2)

• The Numbers of Neutrophils in Induced Sputum-Absolute Neutrophil Count

  The neutrophils play an important role in participants with more severe asthma. The reduction in number of neutrophils in induced sputum was evaluated to study the effect of treatment with repeat oral doses of GSK2190915, in asthma participants. Sputum samples were evaluated at central laboratory. The samples were rejected, if the weight was less than 100 grams (g), or if excessive cell degeneration or due to excessive squamous cells and insufficient inflammatory cells. The total cell count of neutrophil was reported as total cell count × 10\^6 /g.

  Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)

• Percentage of Neutrophils in Induced Sputum

  The neutrophils play an important role in participants with more severe asthma. The reduction in number of neutrophils in induced sputum was evaluated to study the effect of treatment with repeat oral doses of GSK2190915, in asthma participants. Sputum samples were evaluated at central laboratory. The samples were rejected, if the weight was less than 100 g, or if excessive cell degeneration or due to excessive squamous cells and insufficient inflammatory cells. The total cell count of neutrophil was reported as percentage of cells.

  Day -9 to -7, Day 1, Day 12 and follow-up (Day 24-28)

Secondary Outcomes (13)

• Assessment of FEV1 on Visit 2, 3 and Visit 4

  Visit 2 (Day 1), visit 3 (Day 5 to 7) and visit 4 (Day 12)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From visit 1 (Day -7 to Day -9) to upto follow-up (upto Day 28)

• Number of Participants With Vital Sign of Potential Clinical Concern (PCC)

  Visit 2 (Day 1) to Upto follow-up (Day 28)

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings

  Visit 2 (Day 1) to Upto follow-up (Day 28)

• Number of Participants With Clinical Chemistry Values of PCC

  Visit 2 (Day 1) to Upto follow-up (Day 28)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

12 day repeat dosing with placebo

Drug: Placebo

GSK2190915 100mg

EXPERIMENTAL

12 day repeat dosing treatment phase with 100mg GSK2190915.

Drug: GSK2190195 100mg

Interventions

GSK2190195 100mg DRUG

GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor.

GSK2190915 100mg

Placebo DRUG

Placebo : 2% (w/w) Ethanol, sucralose (5 mg/100 mL of oral solution) to 100 % (w/w) aqueous sodium carbonate buffer (0.010 M, pH 9-10)

Placebo

Eligibility Criteria

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

You may qualify if:

• Males and females aged 18 to 65 years inclusive.
• Body mass index within the range 18.5-37.0 kilograms/metre2 (kg/m2).
• An established clinical history of Asthma in accordance with the definition by the GINA Guidelines \[GINA, 2006\]. Subjects should have at screening or within the last year documented reversibility (\>12 %) to short acting bronchodilator, or positive methacholine challenge, or positive histamine challenge (PC20 \<8mg/ml).
• A female subject is eligible to participate if she is of: non-childbearing potential defined as pre-menopausal females with documented (medical report verification) hysterectomy or double oophrectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy; childbearing potential and agrees to use one of the contracception methods listed in Section 8.1 for an appropriate period of time prior to the start of dosing and until 3 months after last dose.
• Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 3 months after the last dose.
• Subject with moderate to severe asthma with forced expiratory volume in one second (FEV1) ≥ 50% of predicted.
• Subject who are on regular inhaled corticosteroids without or in combination with a regular long acting Beta 2 Agonist. The dose should be stable for at least 4 weeks before screening.
• Subjects who are taking a minimum of FP 250mg BID or equivalent.
• Persistent sputum neutrophilia defined by sputum neutrophils ≥ 65% with TTC \< 15 million cells/g with no evidence of eosinophilia (sputum eosinophils \< 2%). Persistent is defined as the criteria being met at screening (or within the 6 months preceding screening) and on visit 1.
• 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:

• 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).
• Clinically significant abnormalities in safety laboratory analysis at screening.
• Subject has uncontrolled hypertension or is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP \>150 mmHg or diastolic BP \> 90mmHg.
• 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 hypercapnoea, respiratory arrest and/or hypoxic seizures.
• Subject is unable to abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti-asthma, anti-rhinitis or hay fever medication, with the exception of ICS, LABA and short action beta agonists, from 14 days before screening until the follow-up visit unless in the opinion of the Investigator and sponsor the medication will not interfere with the study
• Administration of oral or injectable steroids within 6 weeks of screening.
• The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months prior to the first dosing day.
• Administration of anti -leukotrienne therapies for 14 days before screening and during the study.
• Administration of any vaccinations within 1 month 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.
• There is a risk of non-compliance with study procedures.
• History of blood donation (500 mL) within 3 months of starting the clinical study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (8)

GSK Investigational Site

Hamilton, Ontario, L8N 4A6, Canada

Location

GSK Investigational Site

Kingston, Ontario, K7L 2V6, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4J 1C5, Canada

Location

GSK Investigational Site

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

GSK Investigational Site

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

GSK Investigational Site

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

GSK Investigational Site

London, NW10 7EW, United Kingdom

Location

GSK Investigational Site

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study was terminated early due to difficulties in recruiting the required participants.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2009
• First Posted: February 25, 2009
• Study Start: June 26, 2009
• Primary Completion: June 2, 2010
• Study Completion: June 2, 2010
• Last Updated: November 30, 2020
• Results First Posted: March 1, 2018

Record last verified: 2020-11

Locations

GB (4); CA (4)