Inhaled PT007 for Asthma

(MITCHELL Trial)

Recruiting at 22 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: SABA, ICS, LABA

Must not be taking: Oral corticosteroids, Biologics, Tiotropium, others

Disqualifiers: COPD, Life-threatening asthma, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 9 to 17 days

102 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase II study, to investigate the therapeutic efficacy and safety of inhaled PT007 (referred to as AS MDI) compared with placebo MDI and open-label Ventolin Evohaler in male and female participants aged 18 to 65 years (inclusive) with asthma. This study consists of a screening/run-in period, a treatment period, and a follow-up phone call.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you are willing to adjust your asthma therapy as needed. Some medications, like oral corticosteroids and certain biologics, must be stopped before joining the study.

What data supports the effectiveness of the drug PT007 (AS MDI) for asthma?

Research shows that metered-dose inhalers (MDIs), like PT007, are effective in delivering asthma medication, and proper technique is crucial for achieving good results. Additionally, similar treatments using inhalers with fluticasone propionate and salmeterol have been shown to be effective for asthma. ^{1 2 3 4 5}

What safety data exists for inhaled PT007 for asthma?

The safety of albuterol, a similar inhaled medication, was evaluated over 12 and 52 weeks in patients with persistent asthma, showing it to be generally safe. This suggests that inhaled treatments like PT007 may also be safe, but specific data for PT007 is not provided. ^{1 4 6 7 8}

How is the drug PT007 (AS MDI) different from other asthma treatments?

PT007 (AS MDI) is unique because it is an inhaled treatment, which may offer a different particle distribution compared to other forms like dry powder inhalers or nebulizers, potentially improving its effectiveness for certain asthma patients. ^{1 9 10 11 12}

Eligibility Criteria

This trial is for adults aged 18 to 65 with asthma. Specific details about who can join or reasons why someone might not be able to participate are not provided.

Inclusion Criteria

My lung function improved by at least 12% after using Ventolin HFA.

Demonstrate acceptable MDI administration technique. Note: Use of a spacer device during the screening and randomized treatment periods is not permitted.

I can sign and follow the study's consent form and rules.

Exclusion Criteria

I have been hospitalized for asthma in the last 3 months.

I have not been hospitalized for psychiatric reasons or attempted suicide in the last year.

My cold or flu symptoms lasted more than 7 days.

Timeline

Screening/Run-in

Participants are screened for eligibility to participate in the trial

3 to 28 days

1 visit (in-person)

Treatment

Participants receive a single dose of randomized study intervention at each of 3 treatment visits, with a 3- to 7-day washout period between treatment visits

9 to 17 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment via a follow-up phone call

3 to 7 days after the final dose

1 visit (phone call)

Treatment Details

Interventions

• PT007(AS MDI)

Trial Overview The study tests the effectiveness and safety of a new inhaled medication, PT007 (AS MDI), against a placebo inhaler and Ventolin Evohaler. It's a Phase II trial involving screening, treatment period, and follow-up call.

Participant Groups

Group I: Treatment Sequence 6 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Ventolin Evohaler), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007) and Treatment B (Placebo MDI).

Group II: Treatment Sequence 5 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Placebo MDI), Treatment A (Ventolin Evohaler), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007).

Group III: Treatment Sequence 4 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment B (Placebo MDI), Treatment A (Ventolin Evohaler).

Group IV: Treatment Sequence 3 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Placebo MDI), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment A (Ventolin Evohaler).

Group V: Treatment Sequence 2 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment A (Ventolin Evohaler) and Treatment B (Placebo MDI).

Group VI: Treatment Sequence 1 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Ventolin Evohaler) , Treatment B (Placebo MDI), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007).

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a phase III study involving 728 patients with persistent asthma, the novel multidose dry powder inhaler (MDPI) significantly improved lung function (FEV1) and other asthma-related symptoms compared to a placebo.

Both fluticasone propionate (Fp) and fluticasone propionate/salmeterol (FS) delivered via the MDPI were well tolerated and showed a safety profile consistent with existing treatments, with FS MDPI demonstrating superior efficacy over Fp MDPI at certain doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers compared with placebo for persistent asthma. Sher, LD., Yiu, G., Sakov, A., et al.[2018]

In a study involving 50 patients with severe airflow limitation, both metered-dose inhalers (MDI) with a large spacer and nebulized salbutamol showed similar efficacy in improving lung function, as measured by FEV1, after multiple treatments.

The method of delivery (MDI vs nebulization) did not significantly affect the bronchodilator response, indicating that either method can be effectively used for treating acute obstructive pulmonary events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulized wet aerosol treatment in emergency department--is it essential? Comparison with large spacer device for metered-dose inhaler. Mandelberg, A., Chen, E., Noviski, N., et al.[2019]

In a study involving 147 adults with mild-to-moderate persistent asthma, the inhaled corticosteroid budesonide delivered by metered-dose inhaler significantly improved lung function, as measured by morning trough FEV1 and peak expiratory flow rates, particularly at higher doses of 320 μg and 160 μg.

All doses of budesonide were well tolerated and reduced the need for rescue medication, indicating both efficacy and safety, which supports further investigation of the higher doses in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized dose-ranging study of a budesonide metered-dose inhaler by using co-suspension delivery technology in asthma. Miller, SD., Nyberg, J., Siddiqui, S., et al.[2019]

In a phase-3 study involving 640 asthmatic patients, fluticasone propionate/salmeterol (FS) delivered via a multidose dry powder inhaler significantly improved lung function (FEV1) compared to fluticasone propionate (Fp) alone and placebo after 12 weeks.

Both FS and Fp treatments had a similar safety profile to placebo, indicating that they are safe options for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind trial evaluating the efficacy and safety of fluticasone propionate and fluticasone propionate/salmeterol delivered via multidose dry powder inhalers in patients with persistent asthma aged 12 years and older. Raphael, G., Yiu, G., Sakov, A., et al.[2019]

The study demonstrated that while patients' metered-dose inhaler (MDI) technique initially improved with the use of a Vitalograph Aerosol Inhalation Monitor (VAIM) during education, their technique regressed to sub-optimal levels by the 6-week follow-up.

Despite the regression in MDI technique, patients reported significant improvements in physical function, highlighting the importance of ongoing education and support for those using MDIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metered-dose inhaler technique and quality of life with airways disease: assessing the value of the Vitalograph in educational intervention. Skaer, TL., Wilson, CB., Sclar, DA., et al.[2017]

In a study involving patients aged 12 and older with persistent asthma, the albuterol multidose dry powder inhaler (MDPI) demonstrated a safety profile comparable to that of a placebo, with fewer adverse events reported in the albuterol group (40%) compared to the placebo group (50%).

The most common side effects for both albuterol MDPI and placebo were upper respiratory infections and nasopharyngitis, with β2-agonist-related events being very low (≤ 1%), indicating that albuterol MDPI is a safe option for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma. Raphael, G., Taveras, H., Iverson, H., et al.[2018]

The transition from CFC-containing metered dose inhalers (MDIs) to CFC-free alternatives, like Airomir CFC-free, represents a significant advancement in asthma treatment, utilizing hydrofluoroalkane (HFA) 134a as a non-ozone-depleting propellant.

The new CFC-free MDIs have improved dose reproducibility and performance, providing a 'softer puff' and a slightly different taste, while ensuring a seamless experience for patients switching from older CFC MDIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system. Ross, DL., Gabrio, BJ.[2005]

The mometasone furoate/formoterol (MF/F) metered-dose inhaler (MDI) with an integrated dose counter demonstrated high accuracy, with a discrepancy rate of only 0.13 per 100 actuations, significantly lower than the manual counting method (Counterstrip) which had a rate of 1.34 per 100 actuations.

The study, involving 233 subjects over 4 weeks, showed that the MF/F MDI was safe to use, with no reports of new repetitive strain injuries or exacerbations of existing injuries, indicating its ergonomic safety for patients with asthma or COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose counter performance of mometasone furoate/formoterol inhalers in subjects with asthma or COPD. Weinstein, C., Staudinger, H., Scott, I., et al.[2015]

In a study involving 21 adult asthmatic patients, a single dose of salbutamol delivered via a novel multiple dose powder inhaler (MDPI) showed equivalent effectiveness in improving lung function compared to a conventional metered dose inhaler (MDI), with similar spirometric outcomes.

Both inhaler types were well tolerated, with no significant effects on blood pressure or heart rate, and most patients found the MDPI easier or equally easy to use, suggesting it could be a favorable alternative to traditional MDIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Easyhaler, a novel multiple dose powder inhaler: clinically equivalent to salbutamol metered dose inhaler and easier to use. Nieminen, MM., Vidgren, M., Laurikainen, K., et al.[2018]

In a study involving patients with cough variant asthma (CVA) and cough-predominant asthma (CPA), nebulized dexamethasone provided superior symptom control compared to traditional metered-dose inhalers (MDI) or dry powder inhalers (DPI), especially in patients not previously controlled by their current therapy.

Out of the patients treated, 10 out of 12 steroid-independent, 3 out of 6 steroid-dependent, and all 7 acute patients experienced improved symptoms, suggesting that nebulizer therapy may be more effective for certain individuals with asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of nebulized corticosteroids over dry powder inhalers in certain patients with cough variant asthma or cough-predominant asthma. Kamimura, M., Izumi, S., Hamamoto, Y., et al.[2012]

In a study of 57 asthmatic children and teenagers, only 35% correctly followed all five steps for using metered-dose inhalers (MDIs), highlighting a significant gap in proper inhalation technique.

The most common mistakes included failing to take a deep breath (only 35% did this correctly) and not holding their breath for at least 6 seconds (only 54% did this correctly), suggesting a need for better education and training on MDI use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Errors in the technique of using measured-dose inhalers in asthmatic children and adolescents]. de la Rosa López, JH., González Díaz, SN., Canseco González, C., et al.[2015]

In a study involving 40 adult asthmatic patients, both a novel multiple dose powder inhaler (MDPI) and a conventional metered dose inhaler (MDI) delivered salbutamol effectively, showing similar increases in lung function as measured by forced expiratory volume (FEV1).

Both inhaler types were well tolerated with no significant effects on blood pressure or heart rate, and patients generally preferred the MDPI for its ease of use, which may enhance adherence to asthma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical equivalence of a novel multiple dose powder inhaler versus a conventional metered dose inhaler on bronchodilating effects of salbutamol. Vidgren, M., Silvasti, M., Korhonen, P., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers compared with placebo for persistent asthma. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Nebulized wet aerosol treatment in emergency department--is it essential? Comparison with large spacer device for metered-dose inhaler. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized dose-ranging study of a budesonide metered-dose inhaler by using co-suspension delivery technology in asthma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Randomized, double-blind trial evaluating the efficacy and safety of fluticasone propionate and fluticasone propionate/salmeterol delivered via multidose dry powder inhalers in patients with persistent asthma aged 12 years and older. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Metered-dose inhaler technique and quality of life with airways disease: assessing the value of the Vitalograph in educational intervention. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system. [2005]

8. England pubmed.ncbi.nlm.nih.gov

Dose counter performance of mometasone furoate/formoterol inhalers in subjects with asthma or COPD. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Easyhaler, a novel multiple dose powder inhaler: clinically equivalent to salbutamol metered dose inhaler and easier to use. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Superiority of nebulized corticosteroids over dry powder inhalers in certain patients with cough variant asthma or cough-predominant asthma. [2012]

11. Mexico pubmed.ncbi.nlm.nih.gov

[Errors in the technique of using measured-dose inhalers in asthmatic children and adolescents]. [2015]

12. Germany pubmed.ncbi.nlm.nih.gov

Clinical equivalence of a novel multiple dose powder inhaler versus a conventional metered dose inhaler on bronchodilating effects of salbutamol. [2013]