Last updated: 11/07/2018 08:10:55

A study to investigate the effect of SB-705498 on chronic cough

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GSK study ID

114693

See study documents

Clinicaltrials.gov ID

NCT01476098

See results summary

EudraCT ID

2010-021642-22

EU CT Number

Not applicable

Trial status

Study complete

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

Official title: Two part study to investigate pharmacokinetics (PK) & pharmacodynamics (PD) of SB-705498, TRPV1 antagonist, 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

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

Primary purpose:

Treatment

Trial design:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Allocation:

Randomized

Primary outcomes:

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

Maximum observed concentration (Cmax) following 10 hour sampling of a single dose of SB-705498 - Part A

Timeframe: Pre-dose (0.0), 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

Timeframe: Pre-dose (0.0), 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

Timeframe: Baseline(Day -1 ) and Day 1 (2 hours post-dose)

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)

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:

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)

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)

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

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)

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)

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)

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)

Number participants with Adverse Events(AEs) and serious adverse events (SAEs)- Part A

Timeframe: Up to Day 7

Number participants with AEs and SAEs- Part B

Timeframe: up to Day 42

Summary of vital signs -systolic and diastolic blood pressure (Part A)

Timeframe: Up to Day 7

Summary of vital signs -systolic and diastolic blood pressure (Part B)

Timeframe: Up to Day 42

Summary of Vital Signs- Heart rate (Part A)

Timeframe: Up to Day 7

Summary of Vital Signs- Heart rate (Part B)

Timeframe: Up to Day 42

Summary of Vital Signs- Body temperature (Part A)

Timeframe: Up to Day 7

Summary of Vital Signs- Body temperature (Part B)

Timeframe: Up to Day 42

Number of participants with Electrocardiogram (ECG) findings- Part A

Timeframe: Up to Day 7

Number of participants with ECG findings- Part B

Timeframe: Up to Day 42

Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part A

Timeframe: Up to 4 weeks

Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part B

Timeframe: Up to 13 weeks

Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part A

Timeframe: Up to 4 weeks

Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part B

Timeframe: Up to 13 weeks

Interventions:

Drug: Placebo

Drug: SB-705498

Enrollment:

Primary completion date:

2012-19-01

Observational study model:

Not applicable

Time perspective:

Not applicable

Clinical publications:

S. Khalid, R. Murdoch, A. Newlands, K. Smart, A. Kelsall, K. Holt, R. Dockry, A. Woodcock and J. A. Smith.Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: A double-blind randomized controlled trial.J Allergy Clin Immunol.2014;134(1):56-62

Medical condition

Rhinitis

Product

SB705498

Collaborators

Not applicable

Study date(s)

April 2011 to January 2012

Type

Interventional

Phase

Participation criteria

Sex

Female & Male

Age

18 - 75 years

Accepts healthy volunteers

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

A history of gastrointestinal, hepatic, renal or multiple cardiovascular risk factors.
Positive pre-study drug/alcohol screen.

Inclusion and exclusion 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.

Trial location(s)

Location

Status

Location

GSK Investigational Site

Manchester, United Kingdom, M23 9QZ

Status

Study Complete

Study documents

Clinical study report

Available language(s): English

Download document(s)

Scientific result summary

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status

Study complete

Actual primary completion date

2012-19-01

Actual study completion date

2012-19-01

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

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