COPDPhase 1NCT02287272
Drug-drug Interaction Study of CHF5993 With Cimetidine
A Phase 1 study testing CHF 5993 pMDI and Cimetidine plus CHF5993 pMDI in people with COPD, run by Chiesi Farmaceutici S.p.A. at 1 site in Belgium.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- COPD
- What is being tested?
- CHF 5993 pMDI and Cimetidine plus CHF5993 pMDI
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteBelgium
- Study dates
- May 2014to Sep 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the detailed description
the safety and tolerability of study treatments based on evaluation of vital signs, electrocardiograms and clinical laboratory assessments will be also evaluated.
- Conditions
- COPD
- Being tested
- CHF 5993 pMDI, Cimetidine plus CHF5993 pMDI
- Keywords
- COPD- cimetidine- drug-drug interaction
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHF 5993 pMDIDrug
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
Cimetidine plus CHF5993 pMDIDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Treatment period R | Active comparator | single inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination) Receives: Drug: CHF 5993 pMDI |
| 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) Receives: Drug: Cimetidine plus CHF5993 pMDI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) of Glycopyrronium Bromide
Measured: pre-dose, 5, 10,15,30min, 1,2,4,6,8,12hr post-dose
Secondary outcomes (3)
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
Measured: pre-dose-72hr post-dose
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
Measured: 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
Measured: pre-dose- 72hr post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2014 (estimated)
- Study startMay 2014
- Primary completionJul 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wouter Haazen, MD, Principal investigator, Life Science Services SGS Belgium NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02287272
- Sponsor's protocol ID
- CCD-05993AA1-12
- Other IDs
- 2013-005491-18
- Status last verified
- Oct 2021
- First submitted
- 20 May 2014
- Last updated
- 29 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27209586
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02287272
- Acronym / sponsor ID
- CCD-05993AA1-12
- Conditions
- COPD
- Keywords
- COPD- cimetidine- drug-drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Study start
- May 2014
- Primary completion
- Jul 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 10 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment period R | Active comparator | Drug: CHF 5993 pMDIsingle inhaled dose of CHF 5993 pMDI (BDP/FF/GB fixed dose combination) |
| Treatment period T | Active comparator | Drug: Cimetidine plus CHF5993 pMDICimetidine 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) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CHF 5993 pMDI4 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 | Drug | Treatment period R |
| Cimetidine plus CHF5993 pMDICimetidine 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) | Drug | Treatment period T |
Primary outcome
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
3 secondary outcomes
Other pharmacokinetic parameters for Glycopyrronium Bromide
Time frame: pre-dose-72hr post-dose
Other pharmacokinetic parameters for Formoterol
Time frame: pre-dose-24hr post dose
Other pharmacokinetic parameters for B17MP
Time frame: pre-dose- 72hr post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2021.
- Results publication: PubMed 27209586Mariotti 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wouter Haazen, MD principal investigator
Life Science Services SGS Belgium NV
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CHF 5993 pMDI and Cimetidine plus CHF5993 pMDI in people with COPD, run by Chiesi Farmaceutici S.p.A. at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02287272, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2021.