This study is designed to loook at the affect of oral SB-705498 on cough following an inhaled capsaicin challenge
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
21
GSK Investigational Site
Manchester, United Kingdom
Pharmacokinetic parameter of area under the plasma concentration-time curve from time zero to 4 hours AUC(0-4) and from time zero (pre-dose) to last time of quantifiable concentration AUC(0-t)- Part A
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.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
Maximum observed concentration (Cmax) following 10 hour sampling of a single dose of SB-705498 - Part A
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.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose Day 1
Time of occurrence of Cmax (Tmax) following 10 hour sampling of a single dose of SB-705498 -Part A
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.
Time frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
Capsaicin concentration required to achieve Five or more coughs (C5) following a single dose of SB-705498 at Tmax as compared to baseline- Part A
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).
Time frame: Day -1 (baseline) and Day 1 (2 hours post dose
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Capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo- Part B
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).
Time frame: Day -1, Day 1 (2hrs and 24 hrs post dose)
Cough Count Per 24 hour following single dose of SB-705498 as compared to placebo- Part B
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.
Time frame: Day -1 and Day 1 (2 and 24 hours)
Capsaicin concentration required to achieve two or more coughs (C2) following a single dose of SB-705498 at Tmax as compared to baseline- Part A
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).
Time frame: Day -1 and Day 1 (2 hours post dose)
Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at Tmax as compared to baseline- Part B
Time frame: Day 1 (2 and 24 hours post dose)
Changes in the Cough Quality of Life Questionnaire (CQLQ) following a single dose of SB-705498 compared to placebo- Part B
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.
Time frame: Day -1 and 14
Urge to cough Visual Analogue Scale (VAS) following single dose of SB-705498- Part B
VAS following single dose of SB-705498 was summarized on Day -1, and Day 1 pre-dose, 2 and 24 hours.
Time frame: Day -1 and Day 1 (pre-dose 2 and 24 hours)
Capsaicin concentration required to achieve C5 following a single dose of SB-705498 at 24 hours as compared to baseline-Part B
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).
Time frame: Day -1 and Day 1 (2 and 24 hours post dose)
Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at 24 hours as compared to baseline- Part B
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).
Time frame: Day -1 and Day 1 (2 and 24 hours post dose)
The 24-hour cough count (rate) subdivided by day and night cough counts (rates) to give day/night specific values by treatment group-Part B
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.
Time frame: Up to Day 2 (Period 2)
Number participants with Adverse Events(AEs) and serious adverse events (SAEs)- Part A
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.
Time frame: Up to Day 7
Number participants with AEs and SAEs- Part B
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.
Time frame: up to Day 42
Summary of vital signs -systolic and diastolic blood pressure (Part A)
Systolic and diastolic blood pressure was assessed on pre dose and 2, 10 hours post dose.
Time frame: Up to Day 7
Summary of vital signs -systolic and diastolic blood pressure (Part B)
Systolic and diastolic blood pressure was assessed on pre dose and 4 hours post dose.
Time frame: Up to Day 42
Summary of Vital Signs- Heart rate (Part A)
Heart rate was assessed on pre dose and 2, 10 hours post dose.
Time frame: Up to Day 7
Summary of Vital Signs- Heart rate (Part B)
Heart rate was assessed on pre dose and 4 hours post dose.
Time frame: Up to Day 42
Summary of Vital Signs- Body temperature (Part A)
Body temperature was measured with a tympanic thermometer at pre-dose, 1, 2, 4, 10 hours post dose.
Time frame: Up to Day 7
Summary of Vital Signs- Body temperature (Part B)
Body temperature was measured with a tympanic thermometer at pre-dose, 1, 2, 4, 24 hours post dose.
Time frame: Up to Day 42
Number of participants with ECG findings- Part A
Single 12-lead ECGs was obtained at each time point during the study using an ECG machine. Participants with abnormal values have been presented.
Time frame: Up to Day 7
Number of participants with ECG findings- Part B
Single 12-lead ECGs was obtained at each time point during the study using an ECG machine. Participants with abnormal values have been presented.
Time frame: Up to Day 42
Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part A
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).
Time frame: Up to 4 weeks
Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part B
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).
Time frame: Up to 13 weeks
Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part A
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).
Time frame: Up to 4 weeks
Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part B
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).
Time frame: Up to 13 weeks