Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-005491-18 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to evaluate the pharmacokinetic interaction when CHF5993 (pressurized metered-dose inhaler (pMDI) is administered with Cimetidine (probe inhibitor of the organic cation transport in the kidneys), by comparing the systemic exposure (AUC0-t) of Glycopyrronium Bromide (GB), after a single dose of the fixed combination CHF 5993 pMDI administered alone or at steady-state of Cimetidine
the safety and tolerability of study treatments based on evaluation of vital signs, electrocardiograms and clinical laboratory assessments will be also evaluated.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment period R | Active Comparator | single inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination) |
|
| Treatment period T | Active Comparator | Cimetidine plus CHF5993 pMDI: repeated doses of oral cimetidine for 6 days plus a single inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CHF 5993 pMDI | Drug | 4 inhalations of CHF 5993 pMDI (BDP/FF/GB 100/6/25 micrograms per actuation) giving a total dose of 400, 24, 100 micrograms of BDP, FF, GB |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) of Glycopyrronium Bromide | pre-dose, 5, 10,15,30min, 1,2,4,6,8,12hr post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Other pharmacokinetic parameters for Glycopyrronium Bromide | Area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72) and 0 hours to infinity (AUC0-inf); maximum concentration (Cmax), time to maximum concentration (tmax), and apparent systemic clearance (CL/F) of Glycopyrronium Bromide | pre-dose-72hr post-dose |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) documented amenorrhea or are willing to use one or more of the following reliable *methods of contraception:
Blood donation (equal or more than 450 ml) or blood loss less than 8 weeks before inhalation of the study medication;
Positive HIV1 or HIV2 serology;
Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C;
History of substance abuse or drug abuse within 12 months prior to screening visit or with a positive urine drug screen at screening;
An abnormal triplicate 12-lead ECG (QRS> 120 msec, PR> 220 msec, HR < 40 bpm, HR > 110 bpm) at screening or at randomization;
Subjects whose electrocardiogram (12-lead ECG) shows QTcF >450 ms for males and >470 for females at screening or at randomization;
Subjects whose DBP is higher than 90 mmHg or SBP is higher than 140 mmHg at screening or at randomization;
Subjects who received any investigational new drug, or participated in clinical study within the last 8 weeks before screening;
History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial;
Treatment within the previous 3 months before the screening visit until the end of the study procedures in the last treatment period with any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole);
Subjects who refuse to abstain from alcohol or xanthine containing foods or beverages or grapefruit containing foods or beverages from 48 hour prior to each intake of study medication until the end of confinement at the clinical centre;
Heavy caffeine drinker (> 5 cups or glasses of caffeinated beverages e.g., coffee, tea, cola per day);
Subjects who have a positive urine test for cotinine at screening.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Wouter Haazen, MD | Life Science Services SGS Belgium NV | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Life Science Services SGS Belgium NV | Antwerp | 2060 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27209586 | Result | Mariotti F, Ciurlia G, Spaccapelo L, Muraro A, Acerbi D. A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993. Eur J Drug Metab Pharmacokinet. 2017 Apr;42(2):269-279. doi: 10.1007/s13318-016-0345-2. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| D002927 | Cimetidine |
| ID | Term |
|---|---|
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Cimetidine plus CHF5993 pMDI | Drug | Cimetidine 800 milligrams twice daily for 6 days. On the fourth day, in addition, 4 inhalations of CHF5993 pMDI (BDP/FF/GB total dose 400/24/100 micrograms) |
|
| Other pharmacokinetic parameters for Formoterol |
Area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUC0-t), 0 to 24 hours (AUC0-24), 0 to 72 hours (AUC0-72) and 0 hours to infinity (AUC0-inf); maximum concentration (Cmax), time to maximum concentration (tmax), and apparent systemic clearance (CL/F) of Formoterol |
| pre-dose-24hr post dose |
| Other pharmacokinetic parameters for B17MP | Area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUC0-t), 0 to 24 hours (AUC0-24), 0 to 72 hours (AUC0-72) and 0 hours to infinity (AUC0-inf); maximum concentration (Cmax), time to maximum concentration (tmax), and apparent systemic clearance (CL/F) of B17MP | pre-dose- 72hr post-dose |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |