Trial Outcomes & Findings for Study to Assess the Effect of the New HFA-152a Propellant on Mucociliary Clearance (NCT NCT05875025)

Last Updated: 2024-11-12

Results Overview

MCC rate was assessed by the percent particle retention at 2 hours (PPR2) after the inhalation of radiolabelled particles. Results are shown as adjusted mean (95% CI) for change from baseline in PPR2 (right whole lung) on Day 8, considering either HFA-152a and HFA-134a propellants. PPR2=Percent particle retention at 2 h after the inhalation of radiolabelled particles

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

2 hours post inhalation of radiolabelled particles

Results posted on

2024-11-12

Participant Flow

In total, 20 healthy male and female subjects 18-55y (inclusive) were enrolled according to the inclusion and exclusion criteria. They were randomised, to one of the two sequences with Test (\[T\], HFA-152a propellant) or Reference (\[R\], HFA-134a propellant), i.e. T-R sequence or R-T sequence, with 10 subjects per sequence. All the randomised subjects completed the study.

Participant milestones

Participant milestones
Measure	HFA-152a Followed by HFA-134a HFA-152a and HFA-134a propellant via pressurised metered-dose inhaler (pMDI): Placebo formulated with HFA-152a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8. In this study arm, HFA-152a was used during period 1 and HFA-134a was used during period 2.	HFA-134a Followed by HFA-152a HFA-134a and HFA-152a propellant via pressurised metered-dose inhaler (pMDI): Placebo formulated with HFA-134a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8. In this study arm, HFA-134a was used during period 1 and HFA-152a was used during period 2.
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Assess the Effect of the New HFA-152a Propellant on Mucociliary Clearance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HFA-152a Followed by HFA-134a n=10 Participants HFA-152a and HFA-134a propellant via pressurised metered-dose inhaler (pMDI): Placebo formulated with HFA-152a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8. In this study arm, HFA-152a was used during period 1 and HFA-134a was used during period 2.	HFA-134a Followed by HFA-152a n=10 Participants HFA-134a and HFA-152a propellant via pressurised metered-dose inhaler (pMDI): Placebo formulated with HFA-134a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8. In this study arm, HFA-134a was used during period 1 and HFA-152a was used during period 2.	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34.3 years STANDARD_DEVIATION 8.6 • n=5 Participants	34.4 years STANDARD_DEVIATION 5.9 • n=7 Participants	34.4 years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United Kingdom	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants
Body Mass Index	26.15 kg/m^2 STANDARD_DEVIATION 2.63 • n=5 Participants	24.84 kg/m^2 STANDARD_DEVIATION 2.89 • n=7 Participants	25.50 kg/m^2 STANDARD_DEVIATION 2.77 • n=5 Participants
Smoking status at screening Ex-smoker	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Smoking status at screening Non-smoker	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Lung Function Parameter -- FEV1 (actual value)	3.877 L STANDARD_DEVIATION 0.741 • n=5 Participants	3.974 L STANDARD_DEVIATION 0.730 • n=7 Participants	3.926 L STANDARD_DEVIATION 0.718 • n=5 Participants
FEV1 % of predicted normal value	102.81 percent of predicted STANDARD_DEVIATION 9.38 • n=5 Participants	102.60 percent of predicted STANDARD_DEVIATION 8.55 • n=7 Participants	102.71 percent of predicted STANDARD_DEVIATION 8.74 • n=5 Participants
FVC actual value	4.835 L STANDARD_DEVIATION 0.953 • n=5 Participants	4.963 L STANDARD_DEVIATION 0.895 • n=7 Participants	4.899 L STANDARD_DEVIATION 0.902 • n=5 Participants
FEV1/FVC	0.803 Ratio STANDARD_DEVIATION 0.040 • n=5 Participants	0.802 Ratio STANDARD_DEVIATION 0.037 • n=7 Participants	0.803 Ratio STANDARD_DEVIATION 0.037 • n=5 Participants

PRIMARY outcome

Timeframe: 2 hours post inhalation of radiolabelled particles

Population: The ITT analysis set, defined as all subjects who were randomised and received at least one dose of study treatment (analysed as randomised), included 20 subjects.

Outcome measures

Outcome measures
Measure	Test Propellant n=20 Participants Placebo HFA-152a propellant Placebo formulated with HFA-152a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8	Reference Propellant n=20 Participants Placebo HFA-134a propellant Placebo formulated with HFA-134a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8
Mucociliary Clearance Rate -- Right Whole Lung -- Percent Particle Retention at 2 Hours (PPR2) on Day 8	0.94 percent of particle retention Interval -1.47 to 3.34	-0.42 percent of particle retention Interval -2.82 to 1.98

PRIMARY outcome

Timeframe: 4 hours post inhalation of radiolabelled particles

Population: The ITT analysis set, defined as all subjects who were randomised and received at least one dose of study treatment (analysed as randomised), included 20 subjects.

Mucociliary Clearance rate (MCC) rate, as assessed by the percent particle retention (PPR) (in right whole lung) at 4 h after the inhalation of radiolabelled particles (PPR4), on Day 8. Results are shown as adjusted mean (95% CI) for change from baseline in PPR4 (right whole lung) on Day 8, considering either HFA-152a and HFA-134a propellants. PPR4=Percent particle retention at 4 h after the inhalation of radiolabelled particles

Outcome measures

Outcome measures
Measure	Test Propellant n=20 Participants Placebo HFA-152a propellant Placebo formulated with HFA-152a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8	Reference Propellant n=20 Participants Placebo HFA-134a propellant Placebo formulated with HFA-134a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8
Mucociliary Clearance Rate -- Right Whole Lung -- Percent Particle Retention at 4 Hours (PPR4) on Day 8	-0.58 percent of particle retention Interval -2.29 to 1.14	-1.27 percent of particle retention Interval -2.99 to 0.44

OTHER_PRE_SPECIFIED outcome

Timeframe: Post inhalation of radiolabelled particles; baseline and 4 h after inhalation of the radiotracer on Day 8.

Population: The ITT analysis set, defined as all subjects who were randomised and received at least one dose of study treatment (analysed as randomised), included 20 subjects.

The MCC variables AUC(0-4) was calculated for PPR parameter on the right whole lung region up to 4 h after inhalation of the radiotracer. Results are shown as change from baseline (Day -1) and Day 8, as mean and SD, in percent x hour. AUC(0-4)=Area under the tracheobronchial particle retention curve between 0 and 4 h.

Outcome measures

Outcome measures
Measure	Test Propellant n=20 Participants Placebo HFA-152a propellant Placebo formulated with HFA-152a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8	Reference Propellant n=20 Participants Placebo HFA-134a propellant Placebo formulated with HFA-134a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8
Mucociliary Clearance -- AUC(0-4) -- Right Whole Lung Region	1.093 Percent x h Standard Deviation 5.345	-1.961 Percent x h Standard Deviation 6.402

Adverse Events

Test Propellant

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Reference Propellant

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Test Propellant n=20 participants at risk Placebo HFA-152a propellant Placebo formulated with HFA-152a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8	Reference Propellant n=20 participants at risk Placebo HFA-134a propellant Placebo formulated with HFA-134a propellant via pMDI: 5 inhalations BID (morning and evening) for 8 consecutive days, starting from the morning of Day 1 until the morning of Day 8
Nervous system disorders Headache	10.0% 2/20 • Number of events 2 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	15.0% 3/20 • Number of events 3 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Nervous system disorders Balance Disorder	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Nervous system disorders Presyncope	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Gastrointestinal disorders Abdominal Pain	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Gastrointestinal disorders Nausea	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Hepatobiliary disorders Hypertransaminasaemia	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Injury, poisoning and procedural complications Skin Laceration	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Musculoskeletal and connective tissue disorders Neck Pain	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).
Psychiatric disorders Insomnia	0.00% 0/20 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).	5.0% 1/20 • Number of events 1 • The recording of adverse events (AEs) was the period starting from the time of the Informed Consent signature (Visit 1, Day 2 to 21 before Treatment period 1 (Day-1)) and until the subject's study participation ended at either an Early termination visit or a Follow-up visit or call ( 7-10 days after last intake of study treatment). A follow-up call (or visit) had to be performed in case of early termination as well, if the early termination visit was performed less than 7 days after the intake of the last dose of the study treatment. Safety set was used for the evaluation of AEs. Safety set included all subjects who were randomised and received at least one dose of study drug (HFA-152a or HFA-134a).

Additional Information

Clinical Trial Transparency

Chiesi Farmaceutici S.p.A.

Phone: + 39 0521 2791

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results of this study may be published or presented at scientific meetings. If a publication is presented by the Investigator, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER