A Study to Investigate the Effect of SB-705498 on Chronic Cough

AUC(0-4) is a measure of the average amount of study drug in the blood plasma over a period of 4 hours after the dose and AUC(0-t) is a measure average amount of study drug in the blood plasma over a period of last time of quantifiable concentration. Both the parameters were calculated by standard non-compartmental analysis. Blood samples for PK analysis were obtained at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose.

Cmax is defined as the maximum or "peak" concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. It was calculated by standard non-compartmental analysis. Blood samples for PK analysis were obtained at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose.

Tmax is defined as the time of occurrence of Cmax. Blood samples for PK analysis were obtained at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose.

The concentration of capsaicin required to elicit 5 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

The concentration of capsaicin required to elicit 5 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

24 hour cough count (rate/h) following single dose of SB-705498 as compared to placebo were analyzed by first log transforming the cough counts taken on Day -1 and on Day 1 of each period in the 24 hours post dose. The cough count rates were log(10) transformed.

The concentration of capsaicin required to elicit 2 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

It is a validated, 28-item assessment tool designed to evaluate decrements in quality of life due to chronic cough. This questionnaire measures cough-related symptoms, as well as the social implications and psychological impact. Examples of items include, "I cannot sleep at night" and "I cough and it makes me retch." The final score is obtained by summing the responses to 28 questions, each scored on a 1-4 scale, where 1 is "strongly disagree," and 4 is "strongly agree." The minimum and maximum CQLQ scores are 28 and 112 respectively, with increasing score indicating more severe impairment.

VAS following single dose of SB-705498 was summarized on Day -1, and Day 1 pre-dose, 2 and 24 hours.

The concentration of capsaicin required to elicit 5 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

The concentration of capsaicin required to elicit 2 coughs was analyzed. The distributional properties were investigated, and the endpoint was logged (base 2) for analysis and the difference from Day -1 (baseline) was taken (equivalent to ratio on log scale).

Different cough intervals were investigated, such as a day and night time rate. Participants were treated as a random effect in the model. The mean treatment difference and associated 95% confidence interval was back-transformed to provide a treatment ratio and 95% confidence interval for the ratio.

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Systolic and diastolic blood pressure was assessed on pre dose and 2, 10 hours post dose.

Systolic and diastolic blood pressure was assessed on pre dose and 4 hours post dose.

Heart rate was assessed on pre dose and 2, 10 hours post dose.

Heart rate was assessed on pre dose and 4 hours post dose.

Body temperature was measured with a tympanic thermometer at pre-dose, 1, 2, 4, 10 hours post dose.

Body temperature was measured with a tympanic thermometer at pre-dose, 1, 2, 4, 24 hours post dose.

Single 12-lead ECGs was obtained at each time point during the study using an ECG machine. Participants with abnormal values have been presented.

Single 12-lead ECGs was obtained at each time point during the study using an ECG machine. Participants with abnormal values have been presented.

Hematology PCI values were: White Blood Cell Count; 0.67 (low) and 1.82 (high), Neutrophil Count; 0.83 (low), Hemoglobin (male); 1.03 (high), Hemoglobin (female); 1.13 (high), Hematocrit (male); 1.02 (high), Hematocrit (female); 1.17(high), Platelet Count; 0.67 and 1.57 (high), Lymphocytes; 0.81 (low).

Hematology PCI values were: White Blood Cell Count; 0.67 (low) and 1.82 (high), Neutrophil Count; 0.83 (low), Hemoglobin (male); 1.03 (high), Hemoglobin (female); 1.13 (high), Hematocrit (male); 1.02 (high), Hematocrit (female); 1.17(high), Platelet Count; 0.67 and 1.57 (high), Lymphocytes; 0.81 (low).

Clinical biochemistry PCI values were: Albumin; 0.86 (low), Calcium; 0.91(low) and 1.06 (high), Glucose; 0.71 (low) and 1.41 (high), Potassium; 0.86 (low) and 1.10 (high), Sodium; 0.96(low) and 1.03(high).

Clinical biochemistry PCI values were: Albumin; 0.86 (low), Calcium; 0.91(low) and 1.06 (high), Glucose; 0.71 (low) and 1.41 (high), Potassium; 0.86 (low) and 1.10 (high), Sodium; 0.96(low) and 1.03(high).