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

NCT03859414 | Completed Phase 1

• 2 other identifiers: CLI-05993AB4-012018-003310-40
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma; Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (2)

• 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

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

• Maximum of Concentration (Cmax) of B17MP, FF and GB

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

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

Secondary Outcomes (8)

• Number of Adverse Events (AEs)

  through study completion, an average of 13 weeks

• Number of subjects with Adverse Events

  through study completion, an average of 13 weeks

• Percentage of subjects with Adverse Events

  through study completion, an average of 13 weeks

• Clinical laboratory parameters (biochemistry)

  Over 24 hours after administration

• Clinical laboratory parameters (urinalysis)

  Over 24 hours after administration

Study Arms (4)

Therapeutic Dose 1

ACTIVE COMPARATOR

Single dose administration of CHF 5993 100/6/12.5 µg pMDI 2 inhalations. Total dose of CHF 5993 pMDI = 200/12/25 µg

Drug: Therapeutic Dose 1

Therapeutic Dose 2

ACTIVE COMPARATOR

Single dose administration of CHF 5993 200/6/12.5 µg pMDI 2 inhalations. Total dose of CHF 5993 pMDI = 400/12/25 µg

Drug: Therapeutic Dose 2

Supra-therapeutic Dose

ACTIVE COMPARATOR

Single dose administration of CHF 5993 100/6/12.5 µg pMDI 8 inhalations Total dose of CHF 5993 pMDI = 800/48/100 µg

Drug: Supra-therapeutic Dose

Placebo

PLACEBO COMPARATOR

Single dose administration of CHF 5993 pMDI placebo

Drug: Placebo

Interventions

Therapeutic Dose 1 DRUG

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

Therapeutic Dose 1

Therapeutic Dose 2 DRUG

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

Therapeutic Dose 2

Supra-therapeutic Dose DRUG

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

Supra-therapeutic Dose

Placebo DRUG

CHF 5993 placebo pMDI

Placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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;
• 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).

You may not qualify if:

• 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;
• 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 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);

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Richmond Pharmacology Ltd

London, Tooting, SW17 0RE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34600734 RESULT

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4-way Crossover Assignment

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: March 1, 2019
• Study Start: March 18, 2019
• Primary Completion: July 24, 2019
• Study Completion: July 24, 2019
• Last Updated: October 22, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)