AsthmaPhase 2NCT01160224
Oral GW766944 (Oral CCR3 Antagonist)
A Phase 2 study testing GW766944 in people with Asthma, run by GlaxoSmithKline at 5 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma
- What is being tested?
- GW766944
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 5 sitesCanada
- Study dates
- 8 Sep 2010to 29 Aug 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
GSK Investigational Site
Calgary, Alberta, T2N 4Z6
GSK Investigational Site
Hamilton, Ontario, L8N 4A6
GSK Investigational Site
Montreal, Quebec, H2X 2P4
GSK Investigational Site
Montreal, Quebec, H4J 1C5
GSK Investigational Site
Québec, Quebec, G1V 4G5
About this study
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.
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- GW766944, Placebo
- Keywords
- Asthma, CCR3 receptor antagonists, GW766944
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GW766944Drug
Drug: GW766944 (Active Drug Treatment)
PlaceboOther
Also called Placebo Treatment
This is placebo to match.
| Study group | Role | What they receive |
|---|---|---|
| GW766944 | Active comparator | This is the active drug (GW766944) Receives: Drug: GW766944 |
| Placebo | Placebo comparator | Placebo Arm. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 22
Secondary outcomes (37)
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.
Measured: Day 10
Number of eosinophils (absolute cell count) in blood following prednisone
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: Day 1 (Visit 2), Day 7 (Visit 3) and Day 10 (Visit 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2010 (estimated)
- Study start8 Sep 2010
- Primary completion29 Aug 2011
- Study completion29 Aug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01160224
- Sponsor's protocol ID
- 114312
- Status last verified
- Apr 2017
- First submitted
- 10 Jun 2010
- Last updated
- 13 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01160224
- Acronym / sponsor ID
- 114312
- Conditions
- Asthma
- Keywords
- Asthma, CCR3 receptor antagonists, GW766944
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2010 (actual)
- Primary completion
- 29 Aug 2011 (actual)
- Study completion
- 29 Aug 2011 (actual)
- First posted
- 12 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GW766944 | Active comparator | Drug: GW766944This is the active drug (GW766944) |
| Placebo | Placebo comparator | Other: PlaceboPlacebo Arm. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (22 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GW766944Drug: GW766944 (Active Drug Treatment) | Drug | GW766944 |
| PlaceboAlso: Placebo TreatmentThis is placebo to match. | Other | Placebo |
Primary outcome
Number of eosinophils (absolute cell count) in induced sputum
Time frame: Day 10
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.
Number of eosinophils (absolute cell count) in induced sputum following predisone
Time frame: Day 22
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.
Number of eosinophils (percentage count) in induced sputum
Time frame: Day 10
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.
Number of eosinophils (percentage count) in induced sputum following prednisone
Time frame: Day 22
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.
37 secondary outcomes
Number of eosinophils (absolute cell count) in blood
Time frame: Day 10
Number of eosinophils (absolute cell count) in blood following prednisone
Time frame: Day 22
Eosinophil progenitors in sputum and blood
Time frame: Day 1, Day 10
Chemotactic effect of sputum supernatant on eosinophils
Time frame: Day 10
Provocative concentration of methacholine resulting in a 20 percent reduction (PC 20) in forced expiratory volume in 1 second (FEV1).
Time frame: Day 10
Change from baseline in forced expiratory volume in 1 second (FEV1)
Time frame: From Baseline (Day 1) to Day 10 and Day 17
Change from baseline in FEV1 following prednisone
Time frame: Baseline (Day 1) to Day 22
Assessment of asthma stability using Asthma Control Questionnaire (ACQ)
Time frame: Day 1 and Day 10
Assessment of vital sign systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Time frame: Upto Day 22
Assessment of vital sign heart rate
Time frame: Upto Day 22
Number of participants with abnormal electrocardiogram (ECG) findings
Time frame: Day 1 and Day 10
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time frame: From start of first dose of study drug, Day 1 to upto Day 17
Number of participants with AEs and SAEs following prednisone
Time frame: 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
Time frame: Day 10
Assessment of clinical chemistry parameters albumin and Total protein following prednisone
Time frame: Day 22
Assessment of clinical chemistry parameters creatinine and uric acid
Time frame: Day 10
Assessment of clinical chemistry parameters creatinine and uric acid following prednisone
Time frame: Day 22
Assessment of hematology parameters basophils, eosinophils, lymphocytes, monocytes, total absolute neutrophil count (TANC),platelet count (PC),white blood cell count (WBC)
Time frame: Day 10
Assessment of hematology parameters basophils, eosinophils, lymphocytes, monocytes, TANC, PC, WBC following prednisone
Time frame: Day 22
Assessment of clinical chemistry parameters calcium, chloride ,carbon dioxide content/bicarbonate, glucose, potassium, sodium ,Urea /Blood urea nitrogen (BUN)
Time frame: Day 10
Assessment of clinical chemistry parameters calcium, chloride ,carbon dioxide content/bicarbonate, glucose, potassium, sodium ,Urea / BUN following prednisone
Time frame: Day 22
Assessment of hematology parameters hemoglobin and mean corpuscle hemoglobin concentration (MCHC)
Time frame: Day 10
Assessment of hematology parameters hemoglobin and MCHC following prednisone
Time frame: Day 22
Assessment of hematology parameter hematocrit
Time frame: Day 10
Assessment of hematology parameter hematocrit following prednisone
Time frame: Day 22
Assessment of hematology parameter mean corpuscle hemoglobin (MCH)
Time frame: Day 10
Assessment of hematology parameter MCH following prednisone
Time frame: Day 22
Assessment of hematology parameter mean corpuscle volume (MCV)
Time frame: Day 10
Assessment of hematology parameter MCV following prednisone
Time frame: Day 22
Assessment of hematology parameter red blood cell count (RBC)
Time frame: Day 10
Assessment of hematology parameter RBC following prednisone
Time frame: 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
Time frame: Upto Day 17
Assessment of LFTs alkaline phosphatase, ALT, AST and GGT as a measure of monitoring liver toxicity following prednisone
Time frame: Day 22
Assessment of LFTs direct bilirubin and total bilirubin as a measure of monitoring liver toxicity.
Time frame: Upto Day 17
Assessment of LFTs direct bilirubin and total bilirubin as a measure of monitoring liver toxicity following prednisone
Time frame: Day 22
Assessment of plasma concentrations of GW766994 Pre-dose Day 7 (Visit 3) and Day 10 (Visit 4)
Time frame: 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)
Time frame: Day 1 (Visit 2), Day 7 (Visit 3) and Day 10 (Visit 4)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2017.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GW766944 in people with Asthma, run by GlaxoSmithKline at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of eosinophils (absolute cell count) in induced sputum (time frame: Day 10). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2017; AzTrials last refreshed its copy on 7 Nov 2026.