- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02287272
Drug-drug Interaction Study of CHF5993 With Cimetidine
October 28, 2021 updated by: Chiesi Farmaceutici S.p.A.
Open-label, Randomized, Single Dose, 2-sequence, 2-period Cross-over Study to Investigate the Effect of Inhibition of the Organic Cation Transport in the Kidneys by Cimetidine on the Pharmacokinetics of the CHF5993 in Healthy Volunteers
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
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
the safety and tolerability of study treatments based on evaluation of vital signs, electrocardiograms and clinical laboratory assessments will be also evaluated.
Study Type
Interventional
Enrollment (Actual)
25
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Antwerp, Belgium, 2060
- Life Science Services SGS Belgium NV
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subject's written informed consent obtained prior to any study-related procedure;
- Male and female healthy volunteers aged 18-45 years inclusive;
- Male subjects with female partner of childbearing potential: they or their partner must be willing to use (at least) one or more reliable methods of contraception (see exclusion criterion n.1 for details*) from the time of dose administration and until the end of the study. Male subjects must not donate sperm for 90 days after the last dose of study drug. Male subjects with partners of non-childbearing potential are not required to use contraception;
- Able to understand the study procedures, the risks involved and ability to be trained to correctly use the devices;
- Body Mass Index (BMI) between 18.0 and 30.0 kg/m2 inclusive;
- A serum creatinine within the normal range (0,7-1,2 mg/dL) and an eGFR >80 mL/min/1.73 m2;
- Non- or ex-smokers who smoked < 5 pack years (pack-years = the number of cigarette packs per day times the number of years) and stopped smoking > 1 year;
- Good physical and mental status, determined on the basis of the medical history and a general clinical examination;
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:
- surgical sterilization (e.g. bilateral tubal ligation, hysterectomy for females; vasectomy for males)
- hormonal contraception (implantable, patch, oral), intrauterine device (IUD) or intrauterine system (IUS)
- barrier methods (male or female condom, diaphragm, sponge, cervical cap).
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Treatment period R
single inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination)
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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
|
ACTIVE_COMPARATOR: Treatment period T
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)
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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)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) of Glycopyrronium Bromide
Time Frame: pre-dose, 5, 10,15,30min, 1,2,4,6,8,12hr post-dose
|
pre-dose, 5, 10,15,30min, 1,2,4,6,8,12hr post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Other pharmacokinetic parameters for Glycopyrronium Bromide
Time Frame: pre-dose-72hr post-dose
|
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
|
Other pharmacokinetic parameters for Formoterol
Time Frame: pre-dose-24hr post dose
|
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
Time Frame: pre-dose- 72hr post-dose
|
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
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Wouter Haazen, MD, Life Science Services SGS Belgium NV
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2014
Primary Completion (ACTUAL)
July 1, 2014
Study Completion (ACTUAL)
September 1, 2014
Study Registration Dates
First Submitted
May 20, 2014
First Submitted That Met QC Criteria
November 6, 2014
First Posted (ESTIMATE)
November 10, 2014
Study Record Updates
Last Update Posted (ACTUAL)
October 29, 2021
Last Update Submitted That Met QC Criteria
October 28, 2021
Last Verified
October 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Gastrointestinal Agents
- Cytochrome P-450 Enzyme Inhibitors
- Anti-Ulcer Agents
- Histamine Antagonists
- Histamine Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Histamine H2 Antagonists
- Cimetidine
Other Study ID Numbers
- CCD-05993AA1-12
- 2013-005491-18 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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