Clinical trial NCT01476098: A Study to Investigate the Effect of SB-705498 on Chronic Cough
Official title: Two Part Study to Investigate Pharmacokinetics (PK) & Pharamcodynamics (PD) of SB-705498 in Cough. Part A:Open Label Study in Healthy Subjects to Determine Exposure to SB-705498. Part B:Double-blind, Placebo Controlled, Cross Over Study to Investigate Effect of SB-705498 on Capsaicin Induced Cough and 24 Hour Cough Counts in Cough Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rhinitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-11-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is designed to loook at the affect of oral SB-705498 on cough following an inhaled capsaicin challenge


Eligibility criteria: Inclusion Criteria:

* Male or female between 30 -75 (Part A) and 18-75 (Part B) years of age inclusive.
* Non-child bearing women or women of child bearing potential if they agree to use contraception as indicated by the protocol
* Non-smoker for at least 6 months with a pack history \<5 pack years (Pack years = (No. of cigarettes smoked/day/20) x No. of years smoked).
* Body weight \> 50 kg and body mass index (BMI) within the range 19 - 30.0 kg/m2 (inclusive).
* Capable of giving written informed consent.
* Agree to use contraception listed as acceptable
* Normal 12-lead ECG at screening.
* Chronic cough (Part B only)
* Good general health, apart from chronic cough (part B only), as determined by a responsible physician.

Exclusion Criteria:

* A history of gastrointestinal, hepatic, renal or multiple cardiovascular risk factors.
* Positive pre-study drug/alcohol screen.
* Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
* A positive test for human immunodeficiency virus (HIV) antibody (if determined by the local standard operating procedures (SOPs)).
* History of regular alcohol consumption within 6 months of the study.
* Exposure to more than four new chemical entities within 12 months prior to the start of the study.
* Participation in a clinical trial with a new molecule entity or any other clinical trial within 30 days of the start of the study.
* Use of prescription or non-prescription drugs, as well as of vitamins, herbal and dietary supplements (including St John's Wort) within 7 days prior to study.
* known history of lung cancer
* current treatment with oral corticosteriods or other immunosupressive agents
* FEV1 less than 80% of predicted value at screening
* Any subject who does not reach C5 following 250uM oral capsaicin
* History of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
* Donation of blood or blood products in excess of 500mL within a 56 day period prior the start study.
* Pregnant females as determined by positive serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing.
* Lactating females.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to dosing.

Primary outcomes:
measure: 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
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
measure: Maximum observed concentration (Cmax) following 10 hour sampling of a single dose of SB-705498 - Part A
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose Day 1
measure: Time of occurrence of Cmax (Tmax) following 10 hour sampling of a single dose of SB-705498 -Part A
timeFrame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
measure: 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
timeFrame: Day -1 (baseline) and Day 1 (2 hours post dose
measure: Capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo- Part B
timeFrame: Day -1, Day 1 (2hrs and 24 hrs post dose)
measure: Cough Count Per 24 hour following single dose of SB-705498 as compared to placebo- Part B
timeFrame: Day -1 and Day 1 (2 and 24 hours)
Secondary outcomes:
measure: 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
timeFrame: Day -1 and Day 1 (2 hours post dose)
measure: Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at Tmax as compared to baseline- Part B
timeFrame: Day 1 (2 and 24 hours post dose)
measure: Changes in the Cough Quality of Life Questionnaire (CQLQ) following a single dose of SB-705498 compared to placebo- Part B
timeFrame: Day -1 and 14
measure: Urge to cough Visual Analogue Scale (VAS) following single dose of SB-705498- Part B
timeFrame: Day -1 and Day 1 (pre-dose 2 and 24 hours)
measure: Capsaicin concentration required to achieve C5 following a single dose of SB-705498 at 24 hours as compared to baseline-Part B
timeFrame: Day -1 and Day 1 (2 and 24 hours post dose)
measure: Capsaicin concentration required to achieve C2 following a single dose of SB-705498 at 24 hours as compared to baseline- Part B
timeFrame: Day -1 and Day 1 (2 and 24 hours post dose)
measure: 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
timeFrame: Up to Day 2 (Period 2)
measure: Number participants with Adverse Events(AEs) and serious adverse events (SAEs)- Part A
timeFrame: Up to Day 7
measure: Number participants with AEs and SAEs- Part B
timeFrame: up to Day 42
measure: Summary of vital signs -systolic and diastolic blood pressure (Part A)
timeFrame: Up to Day 7
measure: Summary of vital signs -systolic and diastolic blood pressure (Part B)
timeFrame: Up to Day 42
measure: Summary of Vital Signs- Heart rate (Part A)
timeFrame: Up to Day 7
measure: Summary of Vital Signs- Heart rate (Part B)
timeFrame: Up to Day 42
measure: Summary of Vital Signs- Body temperature (Part A)
timeFrame: Up to Day 7
measure: Summary of Vital Signs- Body temperature (Part B)
timeFrame: Up to Day 42
measure: Number of participants with ECG findings- Part A
timeFrame: Up to Day 7
measure: Number of participants with ECG findings- Part B
timeFrame: Up to Day 42
measure: Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part A
timeFrame: Up to 4 weeks
measure: Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part B
timeFrame: Up to 13 weeks
measure: Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part A
timeFrame: Up to 4 weeks
measure: Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part B
timeFrame: Up to 13 weeks
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: