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

November 30, 2016 updated by: GlaxoSmithKline

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Manchester, United Kingdom, M23 9QZ
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Arm 1
incremental doses capsaicin
Drug: Placebo
SB-705498 placebo
Drug: SB-705498
400 or 600mg oral SB-705498
Active Comparator: Arm 2
incremenrtal doses casaicin
Drug: Placebo
SB-705498 placebo
Drug: SB-705498
400 or 600mg oral SB-705498

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose
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.
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
Time Frame: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours post-dose Day 1
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.
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
Time Frame: 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.
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
Time Frame: Day -1 (baseline) and Day 1 (2 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).
Day -1 (baseline) and Day 1 (2 hours post dose
Capsaicin concentration required to achieve C5 following a single dose of SB-705498 or placebo- Part B
Time Frame: Day -1, Day 1 (2hrs and 24 hrs 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).
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
Time Frame: Day -1 and Day 1 (2 and 24 hours)
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.
Day -1 and Day 1 (2 and 24 hours)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: Day -1 and Day 1 (2 hours post dose)
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).
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)
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
Time Frame: Day -1 and 14
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.
Day -1 and 14
Urge to cough Visual Analogue Scale (VAS) following single dose of SB-705498- Part B
Time Frame: Day -1 and Day 1 (pre-dose 2 and 24 hours)
VAS following single dose of SB-705498 was summarized on Day -1, and Day 1 pre-dose, 2 and 24 hours.
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
Time Frame: Day -1 and Day 1 (2 and 24 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).
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
Time Frame: Day -1 and Day 1 (2 and 24 hours post dose)
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).
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
Time Frame: Up to Day 2 (Period 2)
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.
Up to Day 2 (Period 2)
Number participants with Adverse Events(AEs) and serious adverse events (SAEs)- Part A
Time Frame: Up to Day 7
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.
Up to Day 7
Number participants with AEs and SAEs- Part B
Time Frame: up to Day 42
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.
up to Day 42
Summary of vital signs -systolic and diastolic blood pressure (Part A)
Time Frame: Up to Day 7
Systolic and diastolic blood pressure was assessed on pre dose and 2, 10 hours post dose.
Up to Day 7
Summary of vital signs -systolic and diastolic blood pressure (Part B)
Time Frame: Up to Day 42
Systolic and diastolic blood pressure was assessed on pre dose and 4 hours post dose.
Up to Day 42
Summary of Vital Signs- Heart rate (Part A)
Time Frame: Up to Day 7
Heart rate was assessed on pre dose and 2, 10 hours post dose.
Up to Day 7
Summary of Vital Signs- Heart rate (Part B)
Time Frame: Up to Day 42
Heart rate was assessed on pre dose and 4 hours post dose.
Up to Day 42
Summary of Vital Signs- Body temperature (Part A)
Time Frame: Up to Day 7
Body temperature was measured with a tympanic thermometer at pre-dose, 1, 2, 4, 10 hours post dose.
Up to Day 7
Summary of Vital Signs- Body temperature (Part B)
Time Frame: Up to Day 42
Body temperature was measured with a tympanic thermometer at pre-dose, 1, 2, 4, 24 hours post dose.
Up to Day 42
Number of participants with ECG findings- Part A
Time Frame: Up to Day 7
Single 12-lead ECGs was obtained at each time point during the study using an ECG machine. Participants with abnormal values have been presented.
Up to Day 7
Number of participants with ECG findings- Part B
Time Frame: Up to Day 42
Single 12-lead ECGs was obtained at each time point during the study using an ECG machine. Participants with abnormal values have been presented.
Up to Day 42
Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part A
Time Frame: Up to 4 weeks
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).
Up to 4 weeks
Number of participants with potential clinical importance (PCI) laboratory assessments- hematology Part B
Time Frame: Up to 13 weeks
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).
Up to 13 weeks
Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part A
Time Frame: Up to 4 weeks
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).
Up to 4 weeks
Number of participants with potential clinical importance (PCI) laboratory assessments- clinical biochemistry Part B
Time Frame: Up to 13 weeks
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).
Up to 13 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 13, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 22, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 1, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 30, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 114693

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Statistical Analysis Plan
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Clinical Study Report
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Informed Consent Form
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Individual Participant Data Set
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Study Protocol
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Annotated Case Report Form
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Dataset Specification
    Information identifier: 114693
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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