Phase 2
Completed N=38
A Study to Assess the Safety and Tolerability of Once Daily Inhaled Doses of GSK573719 Made With Magnesium Stearate in Subjects With Chronic Obstructive Pulmonary Disease(COPD)for 7 Days
Pulmonary Disease, Chronic Obstructive
Source: ClinicalTrials.gov NCT00732472 ↗
Enrolled (actual)
38
Serious AEs
0.0%
Results posted
Feb 2014
Primary outcomePrimary: Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) — 6; 2; 8; 5 participants
Summary
The study drug which is an inhaled bronchodilator (lung airway relaxant)has been given to both healthy volunteers and to COPD patients before. This study will assess a new formulation of GSK573719. Many drugs are known to deteriorate over time. To make the study medicine less likely to deteriorate in its container, it is mixed with an inactive substance that helps to to maintain the quality of the study medicine. Previous studies have looked at GSK573719 with another inactive substance called Cellobiose Octaacetate (COA). This study will be looking at a new formulation of GSK573719 using Magnesium Stearate (MgSt) as the inactive substance. MgSt itself is not a medicine but is approved as a food ingredient and has also has been approved to be used in a number of marketed medical inhalers. The purpose of this study is to assess the safety and tolerability of compound GSK573719 with Magnesium Stearate for once-daily treatment of COPD(Chronic Obstructive Pulmonary Disease). This drug will be given to 2 groups of 12 people for 7 days. Group 1 will receive 250mcg or placebo and group 2 will receive 1000mcg or placebo. Group 2 will not be dosed until at least 6 people have completed dosing in group 1 without any significant safety concerns. The following safety measures will be assessed including: ECGs, heart rate, blood pressure, blood samples for safety labs, lung function and 24 hour monitoring of the heart. We will also take blood and urine samples to measure medication levels in the body.
GlaxoSmithKline will be funding the research and it will be recruiting at Synexus in 7 of their centres in the UK.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE) |
6; 2; 8; 5; 0; 0 | — |
| PRIMARY Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7 |
138.9; 132.8; 137.4; 138.6; 135.1; 134.9 | — |
| PRIMARY Mean Heart Rate (HR) on Days 1 and 7 |
70.9; 68.3; 72.8; 64.7; 68.2; 67.4 | — |
| PRIMARY Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7 |
68.30; 70.56; 71.57; 75.79; 68.99; 70.24 | — |
| PRIMARY Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7 |
5; 3; 6; 6; 4; 7 | — |
| PRIMARY Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7 |
2; 6; 5; 3; 7; 4 | — |
| PRIMARY Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7 |
125.19; 134.08; 127.48; 126.91; 77.47; 75.94 | — |
| PRIMARY Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7 |
1.556; 1.253; 1.562; 1.364; 1.294; 1.059 | — |
| PRIMARY Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period |
18; 33; 33; 29 | — |
| PRIMARY Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7 |
42.3; 43.9; 43.7; 44.1; 43.1; 44.0 | — |
| PRIMARY Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7 |
74.0; 76.8; 69.0; 63.8; 71.6; 73.1 | — |
| PRIMARY Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7 |
2.3; 1.7; 2.0; NA; 2.0; 2.0 | — |
| PRIMARY Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7 |
2.317; 2.329; 2.342; 2.311; 2.320; 2.321 | — |
| PRIMARY Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7 |
NA; NA; NA; NA; NA; NA | — |
| PRIMARY Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7 |
31.92; 32.44; 31.25; 31.70; 31.71; 32.20 | — |
| PRIMARY Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7 |
93.9; 95.9; 91.9; 94.0; 94.0; 94.5 | — |
| SECONDARY Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7 |
0.19675; 0.08134; 0.95719; 0.31951; 0.15527; 1.92508 | — |
| SECONDARY Cmax of UMEC on Day 1 and Day 7 |
0.21654; 0.07915; 1.52835; 0.33206; 0.16448; 2.75864 | — |
| SECONDARY Tmax and Tlastof UMEC on Day 1 and Day 7 |
0.080; 0.250; 0.250; 0.080; 0.165; 0.240 | — |
| SECONDARY Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7 |
1223.6; 669.5; 11854.5; 1756.0; 755.9; 13435.9 | — |
| SECONDARY Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7 |
0.58; 0.37; 1.35; 0.76; 0.34; 1.49 | — |
| SECONDARY Renal Clearance of UMEC on Day 1 and Day 7 |
6.5229; NA; 5.6173; 2.5923; 4.0826; 6.6104 | — |
| SECONDARY Urine Half Life (t1/2) of UMEC on Day 7 |
5.785; 8.299; 7.643 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female between 40 and 75 years of age
- A female subject is eligible to participate if she is of:
- Non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy, bilateral salpingectomy or bilateral oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol 450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
- Third degree heart block or pacemaker.
- Risk factors for torsades des pointes (heart failure NYHA II-IV, familial long QT syndrome).
- Elevated resting blood pressure or a mean blood pressure equal to or higher than 150/90 mmHg at screening. A history of and treatment for hypertension is acceptable provided control has been achieved for > 2 months prior to screening.
- A mean heart rate outside the range 50-100 bpm at screening.
Concurrent medication criteria
- Subject requires treatment with nebulised beta-2 agonist or nebulised anticholinergics.
- Subject has received oral or parenteral corticosteroids within 2 weeks of screening.
- Subject is unable to abstain from long-acting bronchodilators from 48 hours prior to the screening and treatment periods (i.e. the last assessment in the dosing period).
(Note, subjects may resume use of their usual medication in between screening and the treatment period if the restrictions in Section 9 Concomitant Medications and Non-Drug Therapies are followed and provided the long acting bronchodilator component is stopped again 48h or more prior to dosing).
- Subject is receiving co-medication with drugs which are commonly recognised to prolong the QTc interval (e.g. quinolones, amiodorane, disopyramide, quinidine, sotalol, chlorpromazine, haloperidol, ketoconazole, terfenadine, cisapride and terodiline).
- Subject requires regular treatment with oral corticosteroids (prednisolone or equivalent).
- Subject is receiving treatment with beta-blockers, except eye drops.
- Subject is receiving treatment with long-term or short-term oxygen therapy, NIPPV or requires nocturnal positive pressure for sleep apnea.
Data sourced from ClinicalTrials.gov (NCT00732472). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.