Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GW642444
GSK233705 · 17 trials · 2 indications
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General AE/SAE module for a complete list of AEs and SAEs.
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of reticulocytes and RBCs at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation). Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Blood samples were collected for the measurement of total bilirubin, direct bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg.
Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the pre-dose measurement at Day 1 for the respective period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
SBP and DBP were measured at Day 1, Day 8, and Day 14 of the respective treatment period. PD=post-dose. Baseline is defined as the pre-dose measurement at Day 1 for the respective period. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
The electrocardiographic (ECG) parameter QT duration corrected using Fridericia's formula (QTcF) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
The electrocardiographic (ECG) parameter QT duration corrected using Fridericia's formula (QTcF) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative times were used for these observations. For 0-8 hr parameters, treatment, period, participant Baseline, and period Baseline were fitted as fixed effects, and participant was fitted as a random effect. For 0-2 hr parameters, treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. Subject 2308 received VI 25 µg in both treatment periods, and contributed twice to the summary of VI 25 µg (n=28).
Baseline was the most recent result taken on or before pre-dose (Day 1). The analysis was performed using a Repeated Measures Model. This model used all available weighted mean pulse rate values recorded. Change from Baseline was calculated as (Change from Baseline = Assessment value - Baseline value).
The trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. The Baseline FEV1 is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose \[time 0\] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
The forced expiratory volume in one second (FEV1) is the amount of air exhaled in one second after an forceful inspiration. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was defined as the value recorded pre-dose (before dosing) on Day 1. Least square mean change along with standard error has been presented.
| Arm | Type | Description |
|---|---|---|
| COHORT 1 (RANDOMISATION AB or BA) | ACTIVE_COMPARATOR | 8-11 years old; Subjects will be assigned to receive GW642444 25μg or matching placebo (in a 1:1 ratio) in an AB or BA (A= GW64244, B= Placebo) sequence. Following randomisation (AB or BA) subjects will receive a single dose treatment, followed by 7 day washout period. This will then be followed by a repeat dose session of the same treatment (Day 8 and Day 14 in house, Days 9-13 at home). Each subject will then complete the same sequence for the alternative treatment in the second session. There will be a washout period of at least 7 days between the treatment periods. |
| COHORT 2 (RANDOMISATION AB or BA) | ACTIVE_COMPARATOR | 5-7 years old. Subjects will be assigned to receive GW642444 25μg or matching placebo (in a 1:1 ratio) in an AB or BA (A= GW64244, B= Placebo) sequence. Following randomisation (AB or BA) subjects will receive a single dose treatment, followed by 7 day washout period. This will then be followed by a repeat dose session of the same treatment (Day 8 and Day 14 in house, Days 9-13 at home). Each subject will then complete the same sequence for the alternative treatment in the second session. There will be a washout period of at least 7 days between the treatment periods. |
| Arm 1 | EXPERIMENTAL | - |
| Arm 2 | PLACEBO_COMPARATOR | - |
| Arm 3 | EXPERIMENTAL | GSK233705 50mcg |
| Arm 4 | EXPERIMENTAL | GSK233705 100mcg |
| Arm 5 | EXPERIMENTAL | GSK233705 200mcg |
| Arm 6 | PLACEBO_COMPARATOR | Placebo |
| 100 mcg GW642444H | ACTIVE_COMPARATOR | Twice daily in the morning. |
| 400 mcg GW642444H | ACTIVE_COMPARATOR | Twice daily in the morning. |
| 50 mcg salmeterol | ACTIVE_COMPARATOR | Twice daily. |
| placebo | PLACEBO_COMPARATOR | Twice daily |
| GW642444 | EXPERIMENTAL | - |
| Salmeterol | ACTIVE_COMPARATOR | - |
| GW642444 50mcg | EXPERIMENTAL | - |
| GW642444 100mcg | EXPERIMENTAL | - |
| GW642444 200mcg | EXPERIMENTAL | - |
| salmeterol 50mcg | ACTIVE_COMPARATOR | - |
| [14C]GW642444 | EXPERIMENTAL | Single 200μg dose of \[14C\]GW642444 given on Day 1. |
| Long acting muscarinic receptor antagonist (LAMA) | EXPERIMENTAL | Inhaled Long acting muscarinic receptor antagonist (LAMA which is in development as a treatment for Chronic Obstructive Pulmonary Disease. |
| Long acting Beta 2 agonist (LABA) | EXPERIMENTAL | Inhaled Long Acting Beta 2 agonist (LABA) which is in development as a treatment for Chronic Obstructive Pulmonary Disease. |
| LAMA with LABA | EXPERIMENTAL | Inhaled Long Acting Muscarinic receptor Antagonist (LAMA) and a inhaled Long Acting Beta 2 Agonist (LABA), both in development for treatment of Chronic Obstructive Pulmonary Disease and taken in combination. |
| LAMA | EXPERIMENTAL | After randomization subject will inhale either GSK233705 50, 100 or 200 microgram once daily for 7 days. |
| LABA | EXPERIMENTAL | After randomization subject will inhale either 12.5 microgram or 25 microgram GW642444M once daily for 7 days. |
| Period 1 | EXPERIMENTAL | Subjects will receive first placebo, then GSK233705, GW642444 and combination of GSK233705 and GW642444 |
| Period 2 | EXPERIMENTAL | Subjects will receive first combination of GSK233705 and GW642444, then placebo, GSK233705 and GW642444 |
| Period 3 | EXPERIMENTAL | Subjects will receive first GSK233705, then GW642444, combination of GSK233705 and GW642444 and later placebo |
| Period 4 | EXPERIMENTAL | Subjects will receive first GW642444, then combination of GSK233705 and GW642444, placebo, and later GSK233705 |
| GW642444M/lactose | EXPERIMENTAL | GW642444M/lactose 6.25, 25 and 100 microgram, single inhaled dose for two days treatment in each treatment sequence (crossover design) |
| GW642444M/MgSt | EXPERIMENTAL | GW642444M/MgSt 6.25, 25 and 100 microgram, single inhaled dose for two days treatment in each treatment sequence (crossover design) |
| Subjects receiving GSK233705 | EXPERIMENTAL | Each subject will receive one or more ascending doses given as a constant rate IV infusion over 30 minutes and a single oral dose of 250 microgram GSK233705 solution. IV doses will include 30, 70, 110 microgram of GSK233705 at specified time points. |
| Subjects receiving treatment sequence 1 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 1; GSK233705 20 micrograms, GSK233705 100 micrograms, tiotropium and placebo. |
| Subjects receiving treatment sequence 2 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 2; GSK233705 20 micrograms, Placebo, GSK233705 50 micrograms and tiotropium. |
| Subjects receiving treatment sequence 3 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 3; GSK233705 20 micrograms, tiotropium, Placebo and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 4 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 4; GSK233705 20 micrograms, placebo, tiotropium and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 5 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 5; Placebo, tiotropium, GSK233705 20 micrograms and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 6 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 6; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and tiotropium. |
| Subjects receiving treatment sequence 7 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 7; tiotropium, GSK233705 20 micrograms, GSK233705 50 micrograms and Placebo. |
| Subjects receiving treatment sequence 8 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 8; tiotropium, GSK233705 20 micrograms, Placebo and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 9 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 9; GSK233705 20 micrograms, tiotropium, GSK233705 50 micrograms and Placebo. |
| Subjects receiving treatment sequence 10 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 10; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and tiotropium. |
| Subjects receiving treatment sequence 11 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 11; Placebo, GSK233705 20 micrograms, tiotropium, and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 12 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 12; Tiotropium, Placebo, GSK233705 20 micrograms and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 13 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 13; Placebo, GSK233705 20 micrograms, GSK233705 50 micrograms and GSK233705 100 micrograms. |
| Subjects receiving treatment sequence 14 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 14; GSK233705 20 micrograms, placebo, GSK233705 50 micrograms and GSK233705 100 micrograms. |
| Subjects receiving treatment sequence 15 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 15; GSK233705 20 micrograms, GSK233705 100 micrograms, Placebo and GSK233705 50 micrograms. |
| Subjects receiving treatment sequence 16 | EXPERIMENTAL | Eligible subjects will receive treatment sequence 16; GSK233705 20 micrograms, GSK233705 100 micrograms, GSK233705 50 micrograms and Placebo. |
| Name | Type | Description |
|---|---|---|
| GW642444 | DRUG | GW642444 25 μg; Novel dry powder inhaler |
| Placebo | DRUG | Matching placebo; Novel dry powder inhaler |
| GSK233705/GW642444 | DRUG | The combination of the long-acting muscarinic antagonist GSK233705 and the long acting beta agonist GW642444 in a single inhaler. |
| GSK233705 12.5mcg | DRUG | Once daily via dry powder inhaler |
| GSK233705 25mcg | DRUG | once daily via dry powder inhaler |
| GSK233705 50mcg | DRUG | Once daily via dry powder inhaler |
| GSK233705 100mcg | DRUG | Once daily via dry powder inhaler |
| GSK233705 200mcg | DRUG | Once daily via dry powder inhaler |
| GSK233705 | DRUG | - |
| GW642444 (25, 100 & 400 mcg/day) | DRUG | 25, 100 and 400mcg/dose |
| Salmeterol 50mcg | DRUG | Salmeterol 50mcg |
| [14C]GW642444 | DRUG | Single 200μg dose of \[14C\]GW642444 given on Day 1. |
| GSK233705 and GW642444 | DRUG | Inhaled Long acting muscarinic receptor antagonist (LAMA) and a inhaled Long acting Beta 2 agonist (LABA) both in development as treatment for Chronic Obstructive Pulmonary Disease, taken in combination. |
| Magnesium Stearate | DRUG | Magnesium Stearate |
| Tiotropium | DRUG | Tiotropium will be given orally as overfoiled strips of 5 capsules, each containing 18 micrograms of tiotropium (as bromide monohydrate) administered via a HandiHaler device. |
Inclusion Criteria: * Male and pre-menarchial female subjects aged 5-11 years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has yet to begin menses and is considered Tanner Stage 2 or less. * Diagnosis of asthma at least 6 months...
GSK233705 is an investigational inhaled small molecule developed for chronic obstructive pulmonary disease (COPD). It has been studied in both healthy volunteers and patients with COPD, including combination regimens with GW642444. GSK233705 remains in clinical development and is not approved for any indication.
GSK233705 is developed by GSK plc, which trades on the New York Stock Exchange under the ticker GSK. GSK sponsored the clinical program, including Phase 1 and Phase 2 trials of GSK233705 alone and in combination with GW642444.
GSK233705 has completed Phase 2 clinical development. Nine trials have been conducted, all of which are completed, with no active trials. The program includes Phase 1 studies in healthy volunteers and Phase 2 studies in patients with COPD.
GSK233705 has been evaluated in completed trials including NCT00964405, a Phase 1 study in healthy Japanese males; NCT00783003, a Phase 1 study of inhaled GSK233705 and GW642444; NCT00749411, a Phase 2 repeat-dose study in COPD; and NCT00676052, a Phase 2 dose-ranging study in COPD.
No, GSK233705 and GW642444 are distinct compounds. GSK233705 has also been referred to as GSK233705B, and the combination of GSK233705 with GW642444 has been studied together in COPD trials such as NCT00783003 and NCT00749411.