Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Oral GW766944 (Oral CCR3 Antagonist)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01160224
First received: June 10, 2010
Last updated: April 5, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: GW766944
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Compare GW766944 (an Oral CCR3 Receptor Antagonist) Versus Placebo in Patients With Asthma and Sputum Eosinophilia.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of eosinophils in induced sputum. [ Time Frame: Collection at screening (Visit 1) for baseline measure, and post treatment on Day 10 (Visit 4) and post-oral prednisone on Day 22 (Visit 6). ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of blood eosinophils (% count) [ Time Frame: Day Screening, Day 10 & Day 22. ] [ Designated as safety issue: Yes ]
  • Eosinophil progenitors in sputum and blood. [ Time Frame: Day 1, Day 10 & Day 22. ] [ Designated as safety issue: No ]
  • Chemotaxis effect of sputum supernatant on eosinophils. [ Time Frame: Screening & Day 10. ] [ Designated as safety issue: No ]
  • Concentration of methacholine resulting in a 20% reduction in FEV1 as a measure of safety. [ Time Frame: Screening & Day 10. ] [ Designated as safety issue: Yes ]
  • Collection of FEV1 as a measure of safety. [ Time Frame: Screening, Day 1, Day 10, Day 17 and Day 22. ] [ Designated as safety issue: Yes ]
  • Asthma Control Questionnaire as a measure of asthma stability. [ Time Frame: Day 1 & Day 10. ] [ Designated as safety issue: No ]
  • Vital Signs (blood pressure and heart rate) as a measure of safety. [ Time Frame: Screening, Day 1, Day 7 or Day 8, Day 10, Day 17 & Day 22. ] [ Designated as safety issue: Yes ]
  • 12 Lead ECG as a measure of safety. [ Time Frame: Screening, Day 1 & Day 10. ] [ Designated as safety issue: Yes ]
  • Adverse event monitoring for safety. [ Time Frame: Day 1, Day 7 or Day 8, Day 10, Day 17 & Day 22. ] [ Designated as safety issue: Yes ]
  • Laboratory tests to measure safety. [ Time Frame: Screening, Day 10 & Day 22. ] [ Designated as safety issue: Yes ]
  • Liver function tests as a measure of monitoring liver toxicity. [ Time Frame: Screening, Day 1, Day 7 or Day 8, Day 10, Day 17 & Day 22. ] [ Designated as safety issue: Yes ]
  • Plasma concentration of GW766994 [ Time Frame: Pre-dose on Day 7 (or Day 8) & Day 10. ] [ Designated as safety issue: Yes ]
  • Plasma concentration of GW766994 [ Time Frame: One hour post dose on: Day 1, Day 7 or Day 8 & Day 10. ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: September 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GW766944
This is the active drug (GW766944)
Drug: GW766944
Drug: GW766944 (Active Drug Treatment)
Placebo Comparator: Placebo
Placebo Arm.
Other: Placebo
This is placebo to match.
Other Name: Placebo Treatment

Detailed Description:

This will be a multi-centre study. This is a randomized, double-blind, placebo-controlled, parallel-group study, in patients with asthma and eosinophilic bronchitis. Subjects with asthma will be atopic and not on oral prednisone. Inhaled corticosteroids are allowed if on stable dose. All subjects will receive a 5 day course of 30mg daily of oral prednisone after one week stopping study drug.

All subjects will attend screening (Visit 1) at which their eligibility for inclusion will be assessed. Eligible subjects will be randomized to receive either 300 mg of GW766994 twice daily or matching placebo at Day 1 (Visit 2) and will be stratified according to the subject's sputum eosinophil count at Visit 1. Treatment will be 10 days of oral dosing, and subjects will participate in a Day 7 or 8 visit (Visit 3), Day 10 visit (Visit 4 - End of Treatment), followed by a 1 week wash out period (Visit 5 -Follow Up Visit). At Visit 5, all subjects will be given 30 mg oral daily prednisone for 5 days and subjects to return to clinic at a Post Oral Prednisone Visit (Visit 6) at Day 22.

Pharmacodynamic assessments will include both sputum and blood biomarkers and spirometry.

Safety will be assessed by vital sign measurement, electrocardiogram, clinical laboratory tests (hematology, chemistry & urinalysis), clinical monitoring and adverse event reporting. Pharmacokinetic samples will be collected from each subject according to the sample schedule in the timing and events table.

Study will involved sputum biology (progenitors, cell counts). Study will be conducted in Canada only.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Participation in a trial with any drug within 30 days or 5 half-lives (whichever is longer), or participation in a trial with a new chemical entity within 2 months prior to first dose of current study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
  • The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened but not limited to amphetamines, barbiturates, cocaine, opiates, and cannabinoids.

Subjects who use benzodiazepines or other anxiolytic on a regular basis can be included at the discretion of the investigator and in consultation with the GSK medical monitor.

  • Cytochrome P450 3A4 inhibitors including but not limited to antiretrovirals (protease inhibitors) (e.g.indinavir, nelfinavir, ritonavir, saquinavir); imidazole and triazole anti-fungals (e.g.

ketaconazole, itraconazole); macrolide antibiotics (e.g. clarithromycin, erytrhomycin and; telithromycin); calcium channel blockers (diltiazem and verapamil) and nefazodone, 6 weeks before.

  • Consumption of seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160224

Locations
Canada, Alberta
GSK Investigational Site
Calgary, Alberta, Canada, T2N 4Z6
Canada, Ontario
GSK Investigational Site
Hamilton, Ontario, Canada, L8N 4A6
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2X 2P4
GSK Investigational Site
Montreal, Quebec, Canada, H4J 1C5
Canada
GSK Investigational Site
Quebec, Canada, G1V 4G5
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01160224     History of Changes
Other Study ID Numbers: 114312
Study First Received: June 10, 2010
Last Updated: April 5, 2012
Health Authority: Canada: Health Canada

Keywords provided by GlaxoSmithKline:
Asthma
CCR3 receptor antagonists
GW766944

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 24, 2014