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The purpose of this study is to evaluate the effect of single doses of therapeutic and supratherapeutic doses of inhaled CHF 4226 pMDI on ventricular repolarization in healthy subjects compared with placebo.
The secondary purposes of this study are to 1) determine if there is a relationship between the duration of the QTc intervals and the plasma concentrations of carmoterol; 2) expand the available information on plasma pharmacokinetics and urine excretion for inhaled carmoterol at the proposed therapeutic and supra-therapeutic doses; and 3) generate additional safety information.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | Single therapeutic dose of CHF 4226 pMDI |
|
| Treatment B | Experimental | Single supratherapeutic dose of CHF 4226 pMDI |
|
| Treatment C | Placebo Comparator | Single dose of placebo |
|
| Treatment D | Active Comparator | Single dose of moxifloxacin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CHF 4226 pMDI | Drug | Inhaled solution, single therapeutic dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| QTci | ECGs taken every treatment period on day -1 and day +1 at -1, -0.5, -0.25, 0.08, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs |
| Measure | Description | Time Frame |
|---|---|---|
| QTcX interval (subject-specific correction of QTcF, QTcB and QTcH) | ECGs taken every treatment period on day -1 and day +1 at -1, -0.5, -0.25, 0.08, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs | |
| Plasma concentration (AUC, Cmax, Tmax) | Each treatment period on dosing day at -0.75, 0.08, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 hrs |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert I. Cooper, MD | PRACS Institute, Ltd. | Principal Investigator |
| Steven E. Linberg, PhD | Chiesi Farmaceutici S.p.A. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRACS Institute, Ltd. | Fargo | North Dakota | 58104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18094215 | Background | Russell T, Riley SP, Cook JA, Lalonde RL. A perspective on the use of concentration-QT modeling in drug development. J Clin Pharmacol. 2008 Jan;48(1):9-12. doi: 10.1177/0091270007311115. No abstract available. | |
| 18094216 | Background | Garnett CE, Beasley N, Bhattaram VA, Jadhav PR, Madabushi R, Stockbridge N, Tornoe CW, Wang Y, Zhu H, Gobburu JV. Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J Clin Pharmacol. 2008 Jan;48(1):13-8. doi: 10.1177/0091270007307881. |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| CHF 4226 pMDI | Drug | Inhaled solution, single supratherapeutic dose |
|
|
| Placebo | Drug | Inhaled solution, single dose of placebo |
|
| Moxifloxacin | Drug | Tablet, oral, 400mg, single dose |
|
|
| Urinary excretion (Ae) | Each treatment period on day of dosing at -0.75, 0.58 and 24 hours. |
| 18094214 | Background | Bloomfield D, Krishna R. Commentary on the clinical relevance of concentration/QTc relationships for new drug candidates. J Clin Pharmacol. 2008 Jan;48(1):6-8. doi: 10.1177/0091270007312257. No abstract available. |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |