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AsthmaPhase 1NCT03859414

PK of BDP/FF/GB Single-inhaler Triple Therapy in Japanese vs. Caucasians

A Phase 1 study testing Therapeutic Dose 1, Therapeutic Dose 2 and Supra-therapeutic Dose in people with Asthma and Chronic Obstructive Pulmonary Disease, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of conducting this study is to obtain PK data of Beclometasone Dipropionate (BDP)/Beclometasone-17-MonoPropionate (B17MP), Formoterol Fumarate (FF) and Glycopyrronium Bromide (GB) after inhalation of CHF 5993 in Japanese as well as Caucasian healthy subjects under the same setting. Read more about this study

Who is it for?
Ages 20 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Asthma, Chronic Obstructive Pulmonary Disease
What is being tested?
Therapeutic Dose 1, Therapeutic Dose 2 and Supra-therapeutic Dose
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
1 siteUnited Kingdom
Study dates
18 Mar 2019to 24 Jul 2019
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 20 to 55 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;
  • Healthy male and female subjects aged 20 to 55 years inclusive;
  • For Japanese subjects: must be a Japanese subject who has resided outside Japan for no more than 5 years, born in Japan and holding a Japanese passport, with all 4 grandparents Japanese, as confirmed by interview;
  • Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol and to comply with the correct use of the devices specified in this protocol;
  • Body mass index within the range of 18.0 to 25.0 kg/m2 inclusive;
  • Non-smokers or ex-smokers who smoked <5 pack years and stopped smoking >1 year prior to screening;
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  • Subject must be healthy on the basis of physical examination, medical history, vital signs, and 12 -lead digitised Electrocardiogram (12-lead ECG);
  • Vital signs (Blood pressure and body temperature) within normal limits;
  • 12-lead ECG considered as normal;
  • Lung function measurements within normal limits;
  • Women of non-childbearing potential (WONCBP) and women of childbearing potential (WOCBP) fulfilling one of the following criteria: a) WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or b) WOCBP with non-fertile male partners: (contraception is not required in this case).
  • Female subject, except if postmenopausal, must have a negative serum beta-human chorionic gonadotropin at screening and a negative urine pregnancy test at Day -1 prior the first drug administration;
  • Subjects must agree not to donate sperm or ova from the time of the first administration of study medication until three months after the end of the systemic exposure of the study drug or until the last follow-up visit, whichever occurs later;
  • Males fulfilling one of the following criteria: a) Males with pregnant or non-pregnant WOCBP partners: they must be willing to use male condom from the signature of the informed consent and until the follow-up visit or b) Non-fertile male subjects (contraception is not required in this case) or c) Males with partner not of childbearing potential (contraception is not required in this case).

Who cannot join

  • Participation in another clinical trial with an investigational drug in the 90 days or 5 half-lives of non-biological entities of that investigational drug (whichever is longer) preceding the administration of the study drug;
  • Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders that may interfere with successful completion of this study;
  • Any other abnormal findings on vital signs, ECG, physical examination or laboratory evaluation of blood and urine samples that the investigator judges as likely to interfere with the study or pose an additional risk in participating;
  • Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic;
  • History of asthma, including childhood asthma, Chronic Obstructive Pulmonary Disease (COPD) or any other chronic pulmonary diseases or condition;
  • Positive HIV1 or HIV2 serology;
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  • results from the Hepatitis serology at screening which indicates acute or chronic Hepatitis (i.e. positive HB surface antigen (HBsAg), HB core antibody (anti-HBc), or Hepatitis C (positive HCV antibody);
  • Blood donation or blood loss (equal or more than 450 mL), less than 2 months prior to randomisation;
  • Abnormal haemoglobin level defined as <12.0 g/dL in females and <14.0 g/dL in males;
  • Positive urine test for cotinine at screening or prior to randomisation;
  • Unsuitable veins for repeated venepuncture;
  • History or clinical evidence of drug and/or alcohol abuse within 12 months prior to screening and randomisation;
  • Known intolerance/hypersensitivity to any of the excipients/components contained in any of the formulations used in the trial;
  • Taking any drug treatment, including prescribed or Over the Counter (OTC) medicines as well as homeopathic remedies etc., in the 14 days before the screening and prior randomisation, with the exception of occasional paracetamol (maximum 3 g per day with a maximum of 10 g per 14 days for mild non-exclusionary conditions), hormonal contraceptives; hormonal replacement treatment for post-menopausal women, occasional ibuprofen (maximum 1.2 g per day, not to exceed 12 g in the 14 days before the screening);
  • Taking enzyme-inducing drugs, enzyme-inhibiting drugs, biologic drugs or any drug known to have a well-defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole) in the 3 months before screening or prior to randomisation;
  • Heavy caffeine drinker >28 cups/week of coffee or similar caffeinated beverages e.g., tea, cola per day);
  • Bacterial or viral respiratory tract, sinus or middle ear infection affecting health status within 4 weeks prior to randomisation;
  • Night shift workers with night shifts within 8 weeks prior to randomisation and during the study.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Richmond Pharmacology Ltd

    London, Tooting, SW17 0RE

Other trials in United Kingdom

About this study

Official title: A Single-center, Randomized, Double-blind, Single Dose, 4-way Cross-over, Placebo-controlled Ethnic Sensitivity Study to Assess the Pharmacokinetics (PK), Pharmacodynamics (PD), Safety, and Tolerability of Different Dosages of CHF 5993 Pressurized Metered Dose Inhaler (pMDI) in Caucasian and Japanese Healthy Subjects

The purpose of conducting this study is to obtain PK data of Beclometasone Dipropionate (BDP)/Beclometasone-17-MonoPropionate (B17MP), Formoterol Fumarate (FF) and Glycopyrronium Bromide (GB) after inhalation of CHF 5993 in Japanese as well as Caucasian healthy subjects under the same setting.

Read the detailed description

The Study is single-centre, randomized, double-blind, single-dose, 4-way cross-over, placebo-controlled.

The safety, tolerability, PD and PK of CHF 5993 will be assessed in Japanese and Caucasian healthy volunteers.

A total of 32 healthy male and female volunteers are planned to be included where they will receive four different treatments (study drug or placebo) over four treatment periods.

Standard safety assessments will be conducted during the study, including safety blood and urine laboratory tests, liver function tests, vital signs, physical examinations, ECGs, 24-hour Holter and observations of any adverse events. Blood samples will also be collected for PK analysis. Blood and urine samples will be collected for pharmacodynamics analysis.

Being tested
Therapeutic Dose 1, Therapeutic Dose 2, Supra-therapeutic Dose, Placebo
Medical subject headings
Asthma, Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Therapeutic Dose 1Drug

    CHF 5993 100/6/12.5 µg pMDI, fixed combination of BDP 100 µg + FF 6 µg + GB 12.5 µg.

  • Therapeutic Dose 2Drug

    CHF 5993 200/6/12.5 µg pMDI, fixed combination of BDP 200 µg + FF 6 µg + GB 12.5 µg.

  • Supra-therapeutic DoseDrug

    CHF 5993 200/6/12.5 µg pMDI, fixed combination of BDP 200 µg + FF 6 µg + GB 12.5 µg.

  • PlaceboDrug

    CHF 5993 placebo pMDI

Study groups in NCT03859414
Study groupRoleWhat they receive
Therapeutic Dose 1Active comparatorSingle dose administration of CHF 5993 100/6/12.5 µg pMDI 2 inhalations. Total dose of CHF 5993 pMDI = 200/12/25 µg
Receives: Drug: Therapeutic Dose 1
Therapeutic Dose 2Active comparatorSingle dose administration of CHF 5993 200/6/12.5 µg pMDI 2 inhalations. Total dose of CHF 5993 pMDI = 400/12/25 µg
Receives: Drug: Therapeutic Dose 2
Supra-therapeutic DoseActive comparatorSingle dose administration of CHF 5993 100/6/12.5 µg pMDI 8 inhalations Total dose of CHF 5993 pMDI = 800/48/100 µg
Receives: Drug: Supra-therapeutic Dose
PlaceboPlacebo comparatorSingle dose administration of CHF 5993 pMDI placebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Curve (AUC) of B17MP, formoterol and GB

    Area under the plasma concentration versus time curve after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration for B17MP and FF, over 48 hours after administration for GB

  2. Maximum of Concentration (Cmax) of B17MP, FF and GB

    Peak Plasma Concentration after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration for B17MP and FF, over 48 hours after administration for GB

Secondary outcomes (8)
  1. Number of Adverse Events (AEs)

    Assessment of the general safety and tolerability in terms of number of Treatment Emergent Adverse Event (TEAEs), Adverse Drug Reaction (ADRs), serious TEAEs, severe TEAEs and TEAEs leading to study discontinuation and to death.

    Measured: through study completion, an average of 13 weeks

  2. Number of subjects with Adverse Events

    Assessment of the general safety and tolerability in terms number of subjects with TEAEs, ADRs, serious TEAEs, severe TEAEs and TEAEs leading to study discontinuation and to death.

    Measured: through study completion, an average of 13 weeks

  3. Percentage of subjects with Adverse Events

    Assessment of the general safety and tolerability in terms of incidence of TEAEs, ADRs, serious TEAEs, severe TEAEs and TEAEs leading to study discontinuation and to death.

    Measured: through study completion, an average of 13 weeks

  4. Clinical laboratory parameters (biochemistry)

    Assessment of PD profile in terms of plasma cortisol, serum potassium and serum glucose after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration

  5. Clinical laboratory parameters (urinalysis)

    Assessment of PD profile in terms of urine cortisol and creatinine excretion after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration

  6. Heart rate

    Assessment of PD profile in terms of the Heart Rate after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration

  7. 12-lead ECG parameters

    Assessment of pharmacodynamics profile in terms of 12-lead ECG parameters extracted from Holter after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration

  8. Vital signs

    Assessment of pharmacodynamics profile in terms of vital signs (systolic and diastolic blood pressure) after a single-dose administration of CHF 5993 pMDI

    Measured: Over 24 hours after administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2019
  2. Study start18 Mar 2019
  3. Primary completion24 Jul 2019
  4. Study completion24 Jul 2019

Resources

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
Other
Allocation
Randomised
Intervention model
Crossover
Model description
4-way Crossover Assignment
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03859414
Sponsor's protocol ID
CLI-05993AB4-01
Other IDs
2018-003310-40, 2018
Status last verified
Oct 2021
First submitted
18 Feb 2019
Last updated
22 Oct 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cella M, Taubel J, Delestre-Levai I, Tulard A, Vele A, Georges G. Ethnic Sensitivity Study of the Extrafine, Single-Inhaler, Triple Therapy Beclomethasone Dipropionate, Formoterol Fumarate, and Glycopyrronium Bromide Pressurized Metered Dose Inhaler in Japanese and Caucasian Healthy Individuals: A Randomized, Double-Blind, Single-Dose Crossover Study. Clin Ther. 2021 Nov;43(11):1934-1947.e4. doi: 10.1016/j.clinthera.2021.09.001. Epub 2021 Sep 29.

    PubMed 34600734

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Therapeutic Dose 1, Therapeutic Dose 2 and Supra-therapeutic Dose in people with Asthma and Chronic Obstructive Pulmonary Disease, run by Chiesi Farmaceutici S.p.A. at 1 site in United Kingdom.

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 14 inclusion and 18 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 22 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 United Kingdom. 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. Some participants in this study may receive a placebo. 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 Curve (AUC) of B17MP, formoterol and GB (time frame: Over 24 hours after administration for B17MP and FF, over 48 hours after administration for GB). The study lists 2 primary outcomes in all. 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 NCT03859414, 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 22 Oct 2021.

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