Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01899768 | GSK2339345 Hypertussive Challenge Study | PHASE2 | COMPLETED | 16 | — | — | Nov 1, 2013 | Oct 1, 2014 | Apr 5, 2017 | 2 | United Kingdom |
| NCT01587716 | A Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2339345. | PHASE1 | COMPLETED | 36 | — | — | Apr 23, 2012 | Jul 30, 2012 | Jul 26, 2017 | 1 | United Kingdom |
| NCT01494636 | The Safety, Tolerability, PK and PD of GSK2339345 in Healthy Subjects | PHASE1 | COMPLETED | 31 | — | — | Oct 17, 2011 | Mar 15, 2012 | Jun 20, 2017 | 1 | United Kingdom |
Total cough count (8 hours \[hr\] of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first four hours starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Number of coughs in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts recorded post dose of every treatment i.e. placebo or GSK2339345 1000mcg was reported.
Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first 4-hrs starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Transient cough was the total number of coughs experienced in the two mins from the start of the first inhalation of a dose. Number of coughs excluding transient cough in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts excluding transient cough recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported.
To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler.
Measured by 4 point scale, fingertip electrode assessment, sensation to water temperature, adverse events, water swallow test and assessment of gag reflex
Measurement of types of AEs reported, severity and relationship to study drug
Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
24 hour Holter ECG will be taken at screening
Triplicate measurements will be taken at screening and pre-dose, single measurements at all other timepoints
To include haematology and clinical biochemistry assessments
| Arm | Type | Description |
|---|---|---|
| Part A | EXPERIMENTAL | Subjects will receive treatment A (placebo) or treatment B (GSK2339345) in 3 visits of part A (one treatment per visit) in one of the following four sequences: ABA, ABB, BAA, and BAB. |
| Part B | EXPERIMENTAL | Subjects will receive treatment A or treatment B in 2 visits of part B (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 microliter (mcL) of a capsaicin solution of strength ranging from 0.49 micromolar (mcM) to 1000 mcM, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 4 and 5. |
| Part C | EXPERIMENTAL | Subjects will receive treatment A or treatment B in 2 visits of part C (one treatment per visit) in one of the following two sequences: AB and BA. Subjects will then orally inhale 10 mcL of a citric acid solution of strength ranging from 0.03 to 4.0 M, which will be administered using a breath activated dosimeter approximately 5 minutes post-dosing with treatment A or B at Visits 6 and 7. |
| 1. Inhaled GSK2339345/Placebo Single Dose (Cohort 1) | EXPERIMENTAL | administered three ascending doses of GSK2339345 or placebo as a solution via an aqueous droplet inhaler over four treatment periods, with at least 5 days washout between doses |
| 2. Inhaled GSK2339345/Placebo Repeat Dose (Cohort 2) | EXPERIMENTAL | administered a dose of GSK2339345 or placebo, four times a day on two consecutive days. Each subject will receive either GSK2339345 or matching placebo as a solution administered via an aqueous droplet inhaler |
| GSK2339345 (solution) (part A) | EXPERIMENTAL | Part A |
| GSK2339345/ Placebo/ Lidocaine (nebulised) (part B) | EXPERIMENTAL | Part B |
| Name | Type | Description |
|---|---|---|
| GSK2339345 | DRUG | Clear colorless solution in clear glass vial for oral inhalation via aqueous droplet inhaler with unit dose strength of 1000 microgram (mcg) inhaled in two actuations. |
| Placebo | DRUG | Clear colorless solution of 0.9% sodium chloride for oral inhalation via aqueous droplet inhaler inhaled in two actuations. |
| GSK2339345 (Inhaled) Single Dose | DRUG | 250, 1000 and 2000 microgram (proposed doses) |
| Placebo (Inhaled) Single Dose | OTHER | Inhaled 0.9% sodium chloride solution |
| GSK2339345 (Inhaled) Repeat Dose | DRUG | 2000 microgram (proposed dose) administered 4 times a day for two consecutive days |
| Placebo (Inhaled) Repeat Dose | OTHER | Inhaled 0.9% sodium cholride solution |
| GSK2339345 (solution) | DRUG | 3, 6, 15, 30, 60 and 120 micrograms (proposed doses). 2 alternating cohorts of 6 subjects. Each subject to receive 3 ascending doses with washout of at least 48 hours between doses. Rinse, Gargle and Spit. |
| GSK2339345 (nebulised) | DRUG | 25, 100, 250, 1000 and 2000 micrograms (proposed doses). Subjects randomised to receive three ascending doses (with each dose given on two consecutive days). Washout of at least 6 days between treatment periods. Nebulised. |
| Placebo (0.9% sodium chloride solution) | DRUG | Administered on Day 1 of one of the treatment periods in part B. Randomised. Nebulised. |
| Lidocaine | DRUG | 40mg dose. Administered on Day 2 of one of the treatment periods in part B. Randomised. Nebulised. |
Inclusion Criteria * Chronic Idiopathic Cough patients according to the criteria listed below, determined by a responsible and experienced physician, based on a medical evaluation: Idiopathic cough defined as chronic cough resistant to treatment targeted at potential triggers. Chronic cough defined...