A 3-period Crossover Study With GSK573719 as Monotherapy in Adult Subjects With Asthma

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 years and older
• All sexes
• No healthy volunteers
• Adult, Older adult

Trial locations and contacts

43 sites in 6 countries.

About this study

Official title: A Multi-national, Randomized, Double-blind, Placebo-controlled, 3-period Crossover Study With GSK 573719 as Monotherapy in Adult Subjects With Asthma

Conditions

Asthma

Being tested

GSK573719 Active treatment or Placebo, GSK573719 (Sub-group cohort), Salbutamol/Albuterol

Keywords

Asthma, Pharmacokinetics, GSK573719, Adults, Pharmacogenetics

Medical subject headings

Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• GSK573719 Active treatment or PlaceboDrug

  Eligible subjects will be randomised to a sequence of three treatments from 8 possible arms: 7 active drug doses (15.6mcg, 31.25 mc, 62.5mcg 125mcg or 250mcg GSK573719 once daily; 15.6mcg or 31.25 mcg GSK573719 taken twice daily) or matched placebo.

• GSK573719 (Sub-group cohort)Procedure or surgery

  Subjects at selected Sub-group sites (approximately 30% of the total population) will have additional serial assessments and procedures (including blood and urine samples for pharmacokinetic analysis) at the start (Day 1) and at the end (Days 14 and 15) of each treatment period. On Day 14 of each treatment period subjects will remain overnight at the clinic for 24-hour assessments, including spirometry, ECGs, and 24-hour Holter monitoring.

• Salbutamol/AlbuterolDrug

  Salbutamol/Albuterol, short-activing beta agonist provided to all subjects to be taken as needed for the relief of asthma symptoms.throughout the study period, including washout periods

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)

   Dose-response was conducted for both QD and BID UMEC doses on trough FEV1 (measure of lung function, defined as the maximal amount of air that can be forcefully exhaled in 1 second) on D 15. Total daily dose of UMEC was used in the modeling. The null model was the final model. The null model is defined as: CFEV1,ij=(THETA1+ETA1j)*meanBL+(THETA2+ETA1j)*periodBL+EPSij, where CFEV1,ij represents the change from BL in trough FEV1 for participant j measured at period i. THETA1 and THETA2 were the slopes with respect to meanBL and periodBL, respectively. Omegas were the variance of the slopes on meanBL and periodBL (ETA1j, ETA2j) for each participant and Sigma was the variance of the residual errors (EPSij). MeanBL is the mean of the Baseline (BL) which is the FEV1 value recorded pre-dose on D 1 of each TP; periodBL is the difference between the BL and the meanBL in each TP for each participant.

   Measured: Day 15 of each treatment period (up to Study Day 71)

2. Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis was performed using a mixed model, including treatment, period, period Baseline FEV1 and mean Baseline FEV1 as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.

   Measured: Day 15 of each treatment period (up to Study Day 71)

3. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

   An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or 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, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of SAEs.

   Measured: From Baseline until the end of Treatment Period 3 (up to Study Day 70)

4. Number of Participants With Asthma Exacerbations During the Treatment Period

   Worsening of asthma symptoms is monitored throughout the study. Severe exacerbation (deterioration of asthma requiring use of systemic corticosteroids for 3 days, inpatient hospitalization or emergency department visit due to asthma) is an exclusion criterion and requires withdrawal from the study. Asthma symptoms were assessed daily using an electronic diary throughout study.

   Measured: From Baseline until the end of Treatment Period 3 (up to Study Day 70)

5. Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period

   Blood pressure measurement included systolic blood pressure (SBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.

   Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

6. Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period

   Blood pressure measurement included diastolic blood pressure (DBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.

   Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

7. Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period

   Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.

   Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

8. Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period

   Blood samples were collected for the measurement of albumin, total protein, and hemoglobin at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

   Measured: Baseline and Day 14 of each treatment period (up to Study Day 70))

9. Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period

   Blood samples were collected for the measurement of ALP, ALT, AST, CK, GGT, and LDH at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

   Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

10. Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period

    Blood samples were collected for the measurement of direct bilirubin, indirect (ind) bilirubin, total bilirubin, and creatinine at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

    Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

11. Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period

    Blood samples were collected for the measurement of chloride, caron dioxide, glucose, potassium, sodium, and urea/BUN at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

    Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

12. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period

    Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC - Absolute neutrophil [neut] count), platelet, and leucocytes count at Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

    Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

13. Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period

    Blood samples were collected for the measurement of the percentage of basophils, eosinophils, lymphocytes, monocytes, and segmented neutrophils (neut) at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

    Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

14. Change From Baseline in Hematocrit on Day 14 of Each Treatment Period

    Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

    Measured: Baseline and Day 14 of each treatment period (up to Study Day 70)

15. Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period

    Urinalysis parameters included: Urine Bilirubin (UB), Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Nitrite (UN), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative (Neg), Trace (T), 1+, 2+, and 3+, and for UG the result can be read as Neg, T, T or 1/10 G/dL, 1+ or 1/4 G/dL, 3+ or 1 G/dL, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, T, 1+, 2+ and 3+ levels at Day 14.

    Measured: Baseline and Day 14 of each treatment period (up to Study Day 70))

16. Urine pH on Day 14 of Each Treatment Period

    Urine samples were collected for the measurement of urine pH by dipstick method at Day 14. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).

    Measured: Day 14 of each treatment period (up to Study Day 70)

17. Urine Specific Gravity on Day 14 of Each Treatment Period

    Urine samples were collected for the measurement of urine specific gravity by dipstick method at Day 14. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. The reference range is 1.002-1.030.

    Measured: Day 14 of each treatment period (up to Study Day 70)

18. Number of Participants With the Indicated Abnormal Electrocardiogram Findings

    Electrocardiograph measurements performed at Screening (Visit 1) and at Day 1 and Day 14 (pre-dose, 10 minutes post-dose and 2 hours post-dose.of each treatment period). Any clinically significant findings were identified during participant monitoring.

    Measured: Day 14 of each treatment period (up to Study Day 70)

19. Number of Participants With the Indicated 24 Hour Holter Findings

    Twenty-four hour Holter ECG measurements were obtained using a 12-lead Holter monitor. The Holter monitor is worn by the participant for 24 hours, and the monitor continuously records the heart's rhythm while the monitor is worn. Following the 24-hour period, the data from the monitor were downloaded and transmitted to the centralized vendor for analysis and interpretation by a licensed cardiologist. The 24-hour Holter ECG measurements were obtained at during the screening period and on Day 14 of each treatment period. The number of participants with clinically significant change (abnormal or normal) were reported.

    Measured: Day 14 of each treatment period (up to Study Day 70)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted17 Jul 2012 (estimated)
2. Study startMay 2012
3. Primary completionFeb 2013
4. Study completionFeb 2013

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Publications (1)Papers the sponsor has linked to this study.
• 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.