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

NCT01476098 | Completed Phase 2

• 1 other identifier: 114693
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rhinitis

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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).

  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

  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

  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 Outcomes (21)

• 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

  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

  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

  Day -1 and 14

• Urge to cough Visual Analogue Scale (VAS) following single dose of SB-705498- Part B

  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

  Day -1 and Day 1 (2 and 24 hours post dose)

Study Arms (2)

Arm 1

PLACEBO COMPARATOR

incremental doses capsaicin

Drug: Placebo; Drug: SB-705498

Arm 2

ACTIVE COMPARATOR

incremenrtal doses casaicin

Drug: Placebo; Drug: SB-705498

Interventions

Placebo DRUG

SB-705498 placebo

Arm 1; Arm 2

SB-705498 DRUG

400 or 600mg oral SB-705498

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Manchester, M23 9QZ, United Kingdom

Location

Related Links

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MeSH Terms

Conditions

Rhinitis

Interventions

SB 705498

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: November 22, 2011
• Study Start: April 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: December 1, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)