Oral GW766944 (Oral CCR3 Antagonist)

NCT01160224 | Completed Phase 2

• 1 other identifier: 114312
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

GW766994 is a selective, competitive antagonist of the human CC chemokine receptor-3 (CCR3). It is proposed that the inhibition of the CCR3 receptor may provide a treatment for airway inflammation such as in asthma. This will be a double-blind, placebo controlled, parallel group study being conducted to evaluate the effects of GW766994 in subjects with mild-moderate asthma who have high sputum eosinophilia. The primary objective is to compare the effects of GW766994 to placebo on sputum eosinophils.

Conditions

Asthma

Keywords

Asthma; CCR3 receptor antagonists; GW766944

Outcome Measures

Primary Outcomes (4)

• Number of eosinophils (absolute cell count) in induced sputum

  Sputum was collected according to the Hargreave/Nair Sputum Induction procedures.Each site performed their sputum analysis locally. Sputum induction for eosinophils was carried out at screening and Day 10. The absolute cell count of eosinophils in induced sputum has been presented.

  Day 10

• Number of eosinophils (absolute cell count) in induced sputum following predisone

  Sputum was collected according to the Hargreave/Nair Sputum Induction procedures. Each site performed their sputum analysis locally. At Visit 5 (Day 17), all participants were given 30 mg oral daily prednisone for 5 days and participants returned to clinic at a Post Oral Prednisone Visit (Visit 6) at Day 22. Sputum induction for eosinophils was carried out at screening and Post Oral Prednisone Visit (Day 22). The absolute cell count of eosinophils in induced sputum has been presented.

  Day 22

• Number of eosinophils (percentage count) in induced sputum

  Sputum was collected according to the Hargreave/Nair Sputum Induction procedures. Each site performed their sputum analysis locally. Sputum induction for eosinophils was carried out at screening and Day 10. Percentage count of eosinophils in induced sputum has been presented.

  Day 10

• Number of eosinophils (percentage count) in induced sputum following prednisone

  Sputum was collected according to the Hargreave/Nair Sputum Induction procedures. Each site performed their sputum analysis locally. At Visit 5, all participants were given 30 mg oral daily prednisone for 5 days and participants returned to clinic at a Post Oral Prednisone Visit (Visit 6) at Day 22. Sputum induction for eosinophils was carried out at screening and Post Oral Prednisone Visit (Day 22). Percentage count of eosinophils in induced sputum has been presented.

  Day 22

Secondary Outcomes (37)

• Number of eosinophils (absolute cell count) in blood

  Day 10

• Number of eosinophils (absolute cell count) in blood following prednisone

  Day 22

• Eosinophil progenitors in sputum and blood

  Day 1, Day 10

• Chemotactic effect of sputum supernatant on eosinophils

  Day 10

• Provocative concentration of methacholine resulting in a 20 percent reduction (PC 20) in forced expiratory volume in 1 second (FEV1).

  Day 10

Study Arms (2)

GW766944

ACTIVE COMPARATOR

This is the active drug (GW766944)

Drug: GW766944

Placebo

PLACEBO COMPARATOR

Placebo Arm.

Other: Placebo

Interventions

GW766944 DRUG

Drug: GW766944 (Active Drug Treatment)

GW766944

Placebo OTHER

This is placebo to match.

Also known as: Placebo Treatment

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Physician diagnosis of asthma (\>12% improvement in FEV1 with a bronchodilator or PC20 methacholine less than 8 mg/ml) documented within the past 2 years.
• Males and females aged ≥18-75 years inclusive.
• 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\].
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 9.1 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 2 days after the last dose of GW766994.
• Non smoker. Current smokers with a with a pack history of less than 10 years may be enrolled into the study. Subjects who only use chewing tobacco products may be enrolled at the discretion of the Investigator and after consultation with the GSK medical monitor.
• Sputum eosinophils \>4.9%.
• AST, ALT, alkaline phosphatase and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• QTcB or QTcF \< 450 msec assessed within 6 months of the screening visit.
• To be eligible, female patients must have a negative urine pregnancy test.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• The subject is able to understand and comply with protocol requirements, instructions and protocol- stated restrictions.

You may not qualify if:

• Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG.
• Current smokers.
• Subjects unable to produce a technically acceptable sputum sample.
• Sputum TCC \>25 million cells/g.
• Clinically significant hepatic impairment or current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody within 3 months of screening.
• The subject regularly drinks more than 28 units of alcohol in a week, if male or 21 units per week, if female. One unit of alcohol is defined as a medium (125ml) glass of wine, half a pint (250ml) of beer, or one measure (25ml) of spirits.
• Pregnant and lactating women.
• Asthma considered unstable within 2 months prioir to screening.
• Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within the 4 weeks before screening and led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study.
• Baseline post-bronchodilator FEV1 \<50% predicted (spirometry to be done at screening visit).
• Regular oral prednisone use.
• Subjects who have received therapy with monoclonal antibodies within the proceeding 3 months prior to screening visit.
• Co-morbidities that, in the investigator's opinion may interfere with study including systemic inflammatory conditions such as rheumatoid arthritis.
• Donation of blood in excess of 500 mL within a 56-day period prior to dosing

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Calgary, Alberta, T2N 4Z6, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8N 4A6, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 2P4, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4J 1C5, Canada

Location

GSK Investigational Site

Québec, Quebec, G1V 4G5, Canada

Location

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

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: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: July 12, 2010
• Study Start: September 8, 2010
• Primary Completion: August 29, 2011
• Study Completion: August 29, 2011
• Last Updated: April 13, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (5)