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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GW766944 | Active Comparator | This is the active drug (GW766944) |
|
| Placebo | Placebo Comparator | Placebo Arm. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GW766944 | Drug | Drug: GW766944 (Active Drug Treatment) |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of eosinophils (absolute cell count) in blood | Blood samples for analysis of eosinophils were collected on randomization (Day 1) and end of treatment (Day 10). The absolute cell count for number of eosinophils in blood has been presented. | Day 10 |
| Number of eosinophils (absolute cell count) in blood following prednisone |
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Inclusion Criteria:
Exclusion Criteria:
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.
ketaconazole, itraconazole); macrolide antibiotics (e.g. clarithromycin, erytrhomycin and; telithromycin); calcium channel blockers (diltiazem and verapamil) and nefazodone, 6 weeks before.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Calgary | Alberta | T2N 4Z6 | Canada | ||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 114312 | Individual Participant Data Set | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Apr 25, 2017 | |
| Reset | Aug 4, 2017 | |
| Release | Aug 31, 2017 | |
| Unrelease | Yes | |
| Release | Dec 19, 2017 | |
| Unrelease | Aug 15, 2018 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Apr 25, 2017 | Aug 4, 2017 | |||
| Aug 31, 2017 |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| Other |
This is placebo to match. |
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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. Blood samples for analysis of eosinophils were collected on randomization (Day 1) and Post Oral Prednisone Visit (Day 22). The absolute cell count for number of eosinophils in blood has been presented. |
| Day 22 |
| Eosinophil progenitors in sputum and blood | Since only one site collected eosinophil progenitor samples, the data was limited. Sputum and blood eosinophil progenitors analysis (CD34+ and IL5Rα+) was carried out on randomization (Day 1) and end of treatment (Day 10) and Post Oral Prednisone Visit (Day 22). | Day 1, Day 10 |
| Chemotactic effect of sputum supernatant on eosinophils | Sputum was collected according to the Hargreave/Nair Sputum Induction procedures. Each site performed their sputum analysis locally. Chemotactic analysis was performed as spontaneous chemotactic activity (Chemotactic activity of the sputum at several dilutions) and Eotaxin-induced chemotaxis (determination in the presence and absence of a single, pre-defined eotaxin concentration spiked into the sputum). In each case the data was a fluorescence intensity which was proportional to the number of migrated cells. The plate-corrected fluorescence intensities were derived by subtracting the mean basal values for each plate from the non-basal individual values on that plate and has been presented as dilution types: neat; 1:03;1:09: 1:27; spiked. | Day 10 |
| Provocative concentration of methacholine resulting in a 20 percent reduction (PC 20) in forced expiratory volume in 1 second (FEV1). | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants inhaled doubling increments of methacholine until a >=20 percent fall in FEV1 from the saline value was achieved. | Day 10 |
| Change from baseline in forced expiratory volume in 1 second (FEV1) | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Spirometry using FEV1 was performed at Day 1 (visit 2), Day 10 (visit 4), Day 17 (visit 5). Baseline was defined as value at Day 1 (visit 2). Change from baseline was calculated by subtracting the baseline value from the post-randomization values at Days 10 and 17. | From Baseline (Day 1) to Day 10 and Day 17 |
| Change from baseline in FEV1 following prednisone | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. 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. Spirometry using FEV1 was performed at Day 22 (visit 6). Baseline was defined as value at Day 1 (visit 2). Change from baseline was calculated by subtracting the baseline value from the post-randomization value at Days 22. | Baseline (Day 1) to Day 22 |
| Assessment of asthma stability using Asthma Control Questionnaire (ACQ) | The ACQ consists of seven questions that were scored on a seven-point scale from 0 to 6. The response options for all these questions consisted of a 0 (no impairment/limitation) to 6 (total impairment/ limitation) scale. The ACQ score was derived as the mean of the seven questions, where the mean score ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated severity. ACQ was set to missing if any of the seven questions had a missing response. Assessments were carried out on Day 1 (visit 2) and Day 10 (visit 4). | Day 1 and Day 10 |
| Assessment of vital sign systolic blood pressure (SBP) and diastolic blood pressure (DBP) | Vital signs measurements included SBP and DBP assessments carried out on Day 1 (visit 2), Day 7 (visit 3), Day 10 (visit 4), Day 17 (visit 5) & Day 22 (visit 6). | Upto Day 22 |
| Assessment of vital sign heart rate | Vital signs measurements included heart rate assessments carried out on Day 1 (visit 2), Day 7 (visit 3), Day 10 (visit 4), Day 17 (visit 5) & Day 22 (visit 6). | Upto Day 22 |
| Number of participants with abnormal electrocardiogram (ECG) findings | Twelve-lead ECGs were recorded in the supine position at the screening, randomization (Day 1) and end of treatment (Day 10) prior to administration of the dose. An automatic ECG machine was used to calculate the heart rate and measure PR, QRS, QT, and QTc intervals. The abnormal findings were categorized as abnormal- not clinically significant (A-NCS) and Abnormal - clinically significant (A-CS). | Day 1 and Day 10 |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new/exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Assessments were carried out at Day 1 (visit 2), Day 7 (visit 3), Day 10 (visit 4), Day 17 (visit 5). | From start of first dose of study drug, Day 1 to upto Day 17 |
| Number of participants with AEs and SAEs following prednisone | An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease (new/exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant/require medical/surgical intervention. 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. Spirometry using FEV1 was performed at Day 22 (visit 6). | From start of first dose of study drug Day 1 up to follow-up Day 22 |
| Assessment of clinical chemistry parameters albumin and Total protein | Blood samples for clinical laboratory evaluation (chemistry parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The chemistry parameters included assessments for albumin, and total protein. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of clinical chemistry parameters albumin and Total protein following prednisone | Blood samples for clinical laboratory evaluation (chemistry parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The chemistry parameters included assessments for albumin, and total protein. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of clinical chemistry parameters creatinine and uric acid | Blood samples for clinical laboratory evaluation (chemistry parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The chemistry parameters included assessments for creatinine and uric acid. Assessments were performed at screening and Day 10. | Day 10 |
| Assessment of clinical chemistry parameters creatinine and uric acid following prednisone | Blood samples for clinical laboratory evaluation (chemistry parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The chemistry parameters included assessments for creatinine and uric acid. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of hematology parameters basophils, eosinophils, lymphocytes, monocytes, total absolute neutrophil count (TANC),platelet count (PC),white blood cell count (WBC) | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessments for basophils, eosinophils, lymphocytes, monocytes, TANC, PC and WBC. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of hematology parameters basophils, eosinophils, lymphocytes, monocytes, TANC, PC, WBC following prednisone | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessments for basophils, eosinophils, lymphocytes, monocytes, TANC, PC and WBC. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of clinical chemistry parameters calcium, chloride ,carbon dioxide content/bicarbonate, glucose, potassium, sodium ,Urea /Blood urea nitrogen (BUN) | Blood samples for clinical laboratory evaluation (chemistry parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The chemistry parameters included assessments for calcium, chloride ,carbon dioxide content/bicarbonate, glucose, potassium, sodium ,Urea /BUN. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of clinical chemistry parameters calcium, chloride ,carbon dioxide content/bicarbonate, glucose, potassium, sodium ,Urea / BUN following prednisone | Blood samples for clinical laboratory evaluation (chemistry parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The chemistry parameters included assessments for calcium, chloride ,carbon dioxide content/bicarbonate, glucose, potassium, sodium ,Urea /BUN. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of hematology parameters hemoglobin and mean corpuscle hemoglobin concentration (MCHC) | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessments for hemoglobin and MCHC. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of hematology parameters hemoglobin and MCHC following prednisone | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessments for hemoglobin and MCHC. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of hematology parameter hematocrit | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for hematocrit. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of hematology parameter hematocrit following prednisone | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for hematocrit. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of hematology parameter mean corpuscle hemoglobin (MCH) | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for MCH. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of hematology parameter MCH following prednisone | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for MCH. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of hematology parameter mean corpuscle volume (MCV) | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for MCV. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of hematology parameter MCV following prednisone | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for MCV. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of hematology parameter red blood cell count (RBC) | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for RBC. Assessments were performed at screening and Day 10 (visit 4). | Day 10 |
| Assessment of hematology parameter RBC following prednisone | Blood samples for clinical laboratory evaluation (hematology parameters) were obtained at screening and follow-up only. Samples were collected following an overnight fast when feasible. The hematology parameter included assessment for RBC. 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. Assessments were performed at screening and Day 22 (visit 6). | Day 22 |
| Assessment of liver function tests (LFTs) alkaline phosphatase, alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma glutamyl transferase (GGT) as a measure of monitoring liver toxicity | LFTS included alkaline phosphatase, ALT, AST and GGT as a measure of monitoring liver toxicity. Assessment were carried out at Screening, Day 1 (visit 2), Day 7 (visit 3), Day 10 (visit 4), Day 17 (visit 5). | Upto Day 17 |
| Assessment of LFTs alkaline phosphatase, ALT, AST and GGT as a measure of monitoring liver toxicity following prednisone | LFTS included alkaline phosphatase, ALT, AST and GGT as a measure of monitoring liver toxicity. 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. Assessment were carried out at Screening and Day 22 (visit 6). | Day 22 |
| Assessment of LFTs direct bilirubin and total bilirubin as a measure of monitoring liver toxicity. | LTFS included direct bilirubin and total bilirubin as a measure of monitoring liver toxicity. Assessment were carried out at Screening, Day 1 (visit 2), Day 7 (visit 3), Day 10 (visit 4), Day 17 (visit 5). | Upto Day 17 |
| Assessment of LFTs direct bilirubin and total bilirubin as a measure of monitoring liver toxicity following prednisone | LTFS included direct bilirubin and total bilirubin as a measure of monitoring liver toxicity. 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. Assessment were carried out at Screening and Day 22 (visit 6). | Day 22 |
| Assessment of plasma concentrations of GW766994 Pre-dose Day 7 (Visit 3) and Day 10 (Visit 4) | Pharmacokinetic samples were collected from each participant according to the sample schedule on Day 2 (visit 3) and 7 (visit 4). Concentrations of GW766994 in plasma have been and summarized by treatment group and nominal time ( i.e. pre-dose). | Pre-dose Day 7 (Visit 3) and Day 10 (Visit 4) |
| Assessment of plasma concentrations of GW766994 1 hours post-dose on Day 1 (Visit 2), Day 7 (Visit 3) and Day 10 (Visit 4) | Pharmacokinetic samples were collected from each participant according to the sample schedule on Day 1 (visit 2), Day 2 (visit 3) and Day 7 (visit 4). Concentrations of GW766994 in plasma have been and summarized by treatment group and nominal time ( i.e. 1 hour post- dose). | Day 1 (Visit 2), Day 7 (Visit 3) and Day 10 (Visit 4) |
| Hamilton |
| Ontario |
| L8N 4A6 |
| Canada |
| GSK Investigational Site | Montreal | Quebec | H2X 2P4 | Canada |
| GSK Investigational Site | Montreal | Quebec | H4J 1C5 | Canada |
| GSK Investigational Site | Québec | Quebec | G1V 4G5 | Canada |
For additional information about this study please refer to the GSK Clinical Study Register |
| 114312 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114312 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114312 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114312 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114312 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 114312 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| Yes |
| Dec 19, 2017 | Aug 15, 2018 |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |