A phase I study to evaluate an investigational medicinal product for the treatment of asthma, in healthy adult participants.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chiesi Farmaceutici S.p.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

3 Aug 2023 → 15 Dec 2023

Decision date (initial)

2023-07-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To evaluate the lung availability and total systemic exposure of beclometasone dipropionate (BDP) and beclometasone 17-monoproprionate (B17MP) (B17MP; active metabolite of BDP) after administration of CHF 718 200 µg pMDI HFA-152a with the Volumatic® spacer, in comparison with CHF 718 200 µg pMDI HFA-134a with the Volumatic® spacer.

Secondary objectives 2

1. To evaluate additional pharmacokinetic (PK) parameters of BDP and B17MP after administration of CHF 718 200 µg pMDI HFA-152a with the Volumatic® spacer, in comparison with CHF 718 200 µg pMDI HFA-134a with the Volumatic® spacer;
2. To evaluate the general safety and tolerability of the two treatments with different propellants.

Conditions and MedDRA coding

Asthma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject’s written informed consent obtained prior to any study related procedure;
2. Healthy male and female subjects aged 18 to 55 years inclusive;
3. Ability to understand the study procedures, the risks involved and ability to be trained to use the inhalers correctly; subjects will not be included if the training is not completed successfully;
4. Body mass index (BMI) within the range of 19.0 to 30.0 kg/m2 (extremes inclusive) and body weight ≥ 50.0 kg;
5. Non-smokers, or ex-smokers who smoked < 5 pack-years [pack-years = (number of packs per day) x (number of years)] and stopped smoking ≥ 1 year prior to screening;
6. Good physical and mental status, determined on the basis of medical history and a general clinical examination, at screening and before randomisation;
7. Vital signs within normal limits at screening: diastolic blood pressure (DBP) 40-90 mmHg, systolic blood pressure (SBP) 90-140 mmHg extremes included (two measures performed after at least 5 minutes of rest; the mean value must be within the defined range); body temperature < 37.5°C;
8. Twelve-lead digitised electrocardiogram (12-lead ECG) intriplicate considered as normal (40 bpm ≤ heart rate [HR] ≤ 110 bpm, 120 ms ≤ PR interval [PR] ≤ 220 ms, QRS interval [QRS] ≤ 120 ms, QT interval corrected using Fridericia’s formula [QTcF] ≤ 450 ms for males and QTcF ≤ 470 ms for females) at screening visit (the mean value must be within the defined range);
9. Lung function measurements within normal limits at screening (normal values: forced expiratory volume in the 1st second [FEV1]/forced vital capacity [FVC] > 0.70 and FEV1 > 80% predicted);
10. Female subjects fulfilling one of the following criteria: a)Women of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e., postmenopausal or permanently sterile, as per definitions given in APPENDIX 2 and in Section 1.1 of the Clinical Trials Facilitation and Coordination Group guidance. Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per Investigator’s request, postmenopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges). b) Women of childbearing potential (WOCBP) fulfilling one of the following criteria: i. 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; ii. WOCBP with non-fertile male partners (contraception is not required in this case);

Exclusion criteria 10

1. Participation in another clinical study with an investigational drug in the 30 days or five half-lives of that investigational drug (whichever is longer) preceding the administration of the study treatment; a longer and more appropriate time could be considered by the Investigator based on the elimination half-life (t1/2) and/or long-term toxicity of the previous investigational drug;
2. Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders that may interfere with successful completion of this protocol according to the Investigator’s judgment;
3. Clinically relevant abnormal laboratory values at screening suggesting an unknown disease and requiring further clinical investigation, or which may impact the safety of the subject or the evaluation of the result of the study according to the Investigator’s judgment;
4. Subjects with a history of significant respiratory diseases (i.e., history of asthma including childhood asthma);
5. Positive serology test for human immunodeficiency virus (HIV) 1 or HIV2 at screening;
6. Positive results from the hepatitis serology which indicates acute or chronic hepatitis B or hepatitis C at screening (e.g., positive hepatitis B surface antigen [HBsAg], hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid [RNA]);
7. Documented coronavirus disease 2019 (COVID-19) diagnosis within the last 2 weeks, or associated complications/symptoms from this disease, which have not resolved within 2 weeks prior to screening; COVID-19 positive subjects on D-1 of treatment period 1 with no official recovery certificate available;
8. Blood donation or blood loss (≥ 450 mL), less than 2 months prior to screening or prior to randomisation;
9. Abnormal haemoglobin (Hb) level, defined as < 11.0 g/dL in females and < 12.9 g/dL in males, in agreement with the local laboratory normal ranges;
10. Positive urine test for cotinine at screening, or prior to randomisation;

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. BDP and B17MP: AUC0-t and Cmax will be log-transformed and analysed using a linear model including treatment, period, sequence and subject within sequence as fixed effects. The ratios of adjusted geometric means between T versus (vs.) R will be calculated with their 90% two-sided CIs. Bioequivalence between T vs. R will be demonstrated if the CI of the ratio is contained within the acceptance interval of 80%-125%;
2. BDP and B17MP: median tmax will be analysed with the Hodges Lehmann non-parametric estimate of location shift between treatments with its two-sided 90% CI will be provided.

Secondary endpoints 1

1. The following variables will be log-transformed and analysed using the same model as for the primary PK variables: - BDP and B17MP: AUC0-∞ and t½; - BDP: AUC0-30min.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chiesi Farmaceutici S.p.A.

Sponsor organisation

Chiesi Farmaceutici S.p.A.

Address

Via Palermo 26 A

City

Parma

Postcode

43122

Country

Italy

Scientific contact point

Organisation

Chiesi Farmaceutici S.p.A.

Contact name

GLOBAL CLINICAL DEVELOPMENT

Public contact point

Organisation

Chiesi Farmaceutici S.p.A.

Contact name

GLOBAL CLINICAL DEVELOPMENT

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications