Study in Adult Patients With Moderate to Severe Asthma

An Exploratory, Double-blind, Randomised, Multicenter, Psychopharmacological Study in Adult Patients With Moderate to Severe Asthma to Compare Two Pressurised Metered-Dose Inhalers (pMDIs) on Patients' Perception of Asthma Symptoms

This study assessed the influence of pink vs. white pressurized metered-dose inhaler (pMDI) actuators on asthma symptoms perception. There was no prespecified primary objective. The following objectives were assessed:

• Change from baseline in average visual analog scale (VAS) score of the perception of asthma symptoms and burden over the first 7 days and all 14 days in each treatment period (Questions 3-6);
• Change from baseline in AQLQ score after 14 days of treatment in each period;
• Summary measures of psychopharmacological aspects (Questions 7-10);
• Patients' preference and perception of the devices (Questions 11-16);
• Change from baseline in reliever medication use over 14 days of treatment in each period (Question 2).

For both treatment periods, "baseline" for the questionnaire data was the 14-day period prior to the first treatment period, and for AQLQ was the value recorded at Visit 2.

This was a phase IIIb, exploratory, double-blind, randomised, multicentre, psychopharmacological, 2x2 cross-over study in adult subjects with moderate to severe asthma.

A total of 78 randomised subjects in 10 actives centres were involved. The study focused on the psychopharmacological aspects, particularly on the subjects' preference for the device and on the impact of the device's features on subjects' perception of asthma symptoms. Subjects were informed that the study treatments were the same medication they had received before enrolment as maintenance therapy (i.e. Foster® 100/6 µg pMDI), but with differing device characteristics.

The study lasted approximately 6 weeks for each subject and comprised four visits (Visit [V] 1 to V4), including:

• Two face-to-face clinic visits: V1 (Day 1, screening/randomisation visit) and V4 (Day 43);
• Two remote video contact visits: V2 (Day 15) and V3 (Day 29).

After signing the ICF, subjects were screened at the investigational site during the screening/randomisation visit (V1). On the same day, and after checking all inclusion and exclusion criteria, eligible subjects were randomised to one of two study treatment sequences and followed the study treatment sequence as follows:

• From V1 (Day 1), subjects were treated with commercial Foster® 100/6 µg pMDI during the 14-day baseline period;

• From V2 (Day 15), subjects were instructed to take CHF1535 100/6 µg pMDI via Inhaler A and Inhaler B during two consecutive periods of 14 days each (first and second treatment periods) in a sequential way dictated by the randomisation:

  • Either CHF1535 100/6 µg pMDI with Inhaler A then CHF1535 100/6 µg pMDI with Inhaler B; or
  • CHF1535 100/6 µg pMDI with Inhaler B then CHF1535 100/6 µg pMDI with Inhaler A.

The first treatment period started at V2 (Day 15) and the second treatment period started at V3 (Day 29), with the end of study visit taking place at V4 (Day 43). A window of ±1 day was allowed for the dates of all study visits except V1 (Day 1).

Please note that "Change from baseline in average VAS score perceptions of asthma-over the 14 Days of treatment - Question #3" was reported as PRIMARY ENDPOINT to comply with CT.gov register requirements, but it should be considered as an OTHER PRE-SPECIFIED endpoint like the other endpoint listed.

Inclusion Criteria:

• Subject's and/or subject legal representative's written informed consent obtained prior to any study related procedure.
• Age: ≥18 and ≤75 years of age.
• Established diagnosis of permanent asthma for at least 6 months prior to screening/randomisation visit
• Subject on maintenance therapy treated by Foster® (CHF1535 100/6 µg pMDI) for at least 6 months prior to screening/randomisation visit
• Asthma Control Test (ACT) ≥ 20 at screening/randomisation visit.
• Subject must have a cooperative attitude and the ability to be trained to use correctly the diary and answer the Visual Analogue Scale (VAS)
• Subject willing and able to download the application on their personal electronic device to fill in the study e-diary.
• Female subject of non-childbearing potential defined as physiologically incapable of becoming pregnant or female subject + male Partner must be willing to use a highly effective birth control method from the signature of the informed consent and until Visit 4

Exclusion Criteria:

• Pregnant or lactating woman
• History of 'at risk' asthma
• Recent exacerbation
• Non-permanent asthma
• Asthma requiring more than 1 inhaler for maintenance treatment and more than 1 inhaler for reliever treatment.
• Asthma requiring use of biologics
• Respiratory disorders
• Lower tract respiratory infection
• Current smoker or ex-smoker with a smoking current use/history of ≥ 10 pack-years
• Cardiovascular diseases
• Subject with historical or current evidence of uncontrolled concurrent disease such as but not limited to hyperthyroidism, diabetes mellitus or other endocrine disease, haematological disease and autoimmune disorders
• Alcohol/drug abuse
• Participation in an investigational trial within the last 30 days (60 days for biologics) or a more appropriate time as determined by the Investigator
• Contra-indications to Foster® constituted an exclusion criterion
• History of hypersensitivity to Foster® or any of its components or a history of any other allergy that in the opinion of the Investigator contra-indicated the subject's participation
• Subject mentally or legally incapacitated or subject accommodated in an establishment as a result of an official or judicial order
• Blind, colour-blind subject or any other dyschromatopsia
• Known psychiatric disorders that may have interfered with successful completion of this protocol according to the Investigator's judgment including schizophrenia, bipolar disorders and psychoses.