Asthma
Conditions
Keywords
Asthma, Bronchial, Bronchial Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Anti-Asthmatic Agents, Respiratory System Agents
Brief summary
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.
Detailed description
This is a randomized, double-blind, single-dose, placebo-controlled, 3-period, 3-treatment, crossover, multicenter study to assess the bronchodilatory effect and safety of AS MDI (180 μg) compared with placebo MDI and open-label Ventolin Evohaler (200 μg) in adult participants (aged 18 to 65 years, inclusive) with asthma (pre-bronchodilator FEV1 of ≥ 40% of the predicted normal value) and demonstrated FEV1 reversibility to Ventolin hydrofluoroalkane (HFA) (improvement in FEV1 at 30 minutes post-Ventolin HFA dosing of ≥ 12% and ≥ 200 mL). The study duration will be a minimum of 15 days and up to a maximum of 52 days. Including: screening/run-in period: 3 to 28 days treatment period: 9 to 17 days follow-up phone call: 3 to 7 days after the final dose of study intervention Eligible participants will be randomized to 1 of 6 predefined treatment sequences in a 1:1:1:1:1:1 ratio. Each sequence will contain AS MDI, placebo MDI, and Ventolin Evohaler in a randomized order. Eligible participants will receive a single dose of randomized study intervention at each of 3 treatment visits (Visits 2, 3, and 4), with a 3- to 7-day washout period between treatment visits.
Interventions
COMBINATION_PRODUCTIntervention: AS MDI
Drug Treatment: (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007) Randomized participants will receive a single-dose (2 inhalations)
COMBINATION_PRODUCTIntervention: Ventolin Evohaler
Drug: Treatment (Ventolin Evohaler) Randomized participants will receive a single-dose (2 inhalations)
COMBINATION_PRODUCTIntervention: Placebo matching AS MDI
Drug: Treatment (Placebo MDI) Randomized participants will receive a single-dose (2 inhalations to match AS MDI)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
AS MDI and placebo MDI will be blinded to all participants, study site staff, endpoint assessors, and sponsor personnel. Placebo MDI is designed to mimic the appearance, smell, and taste of AS MDI. No double-dummy will be used. Packaging and labelling of AS MDI and placebo MDI will be designed to ensure blinding. The IRT will provide to the investigator(s) or pharmacist(s) the kit identification number to be allocated to the participant at the dispensing visits. Routines for this will be described in the IRT user manual that will be provided to each study site. Randomized Ventolin Evohaler is open label. However, to reduce bias, dosing will be performed under the supervision of study staff, and spirometry assessments will be performed by different study personnel who will only enter the room after dosing is completed; thus, the study personnel conducting the spirometry assessments will be blinded to the identity of the study intervention."
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Age 1. Participant must be aged 18 to 65 years (inclusive), at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Participants should have a documented history of physician-diagnosed asthma ≥ 6 months prior to Visit 1. 3. Must be receiving one of the following required inhaled asthma therapies listed below for at least the last 30 days: 1. Only SABA, which is used as needed for rescue. 2. Low to medium doses of ICS (alone or in combination with LABA), used regularly as maintenance asthma therapy. 4. Pre-BD FEV1 of ≥ 40% of the PN value at Visit 1, after withholding SABA for ≥ 6 hours (and Visit 1a and/or Visit 1b, if applicable). 5. Confirmed FEV1 reversibility to 4 actuations of Ventolin HFA, defined as a post-Ventolin HFA increase in FEV1 at 30 minutes of ≥ 12% and ≥ 200 mL at either Visit 1, Visit 1a, or Visit 1b; only 2 reversibility testing attempts are allowed. 6. Demonstrate acceptable spirometry performance (ie, meet ATS/ERS acceptability/repeatability criteria). 7. Willing and, in the opinion of the investigator, able to adjust current asthma therapy, as required by the protocol. 8. Demonstrate acceptable MDI administration technique. Note: Use of a spacer device during the screening and randomized treatment periods is not permitted. Weight 9. Body mass index \< 40 kg/m2. Sex and Contraceptive/Barrier Requirements 10. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 11. Female participants: A participant of childbearing potential, must have a negative urine pregnancy test at Visit 1 (to be read locally). Participants not of childbearing potential are defined as those who are physiologically incapable of becoming pregnant, including any participant who is 2 years postmenopausal, or surgically sterile (defined as having a bilateral oophorectomy, hysterectomy, tubal ligation, or other permanent birth control measures). Participants aged ≥ 50 years will be considered postmenopausal if they have been amenorrheic for 12 consecutive months or more following cessation of all exogenous hormonal treatment. Participants aged \< 50 years will be considered postmenopausal if they have been amenorrheic for 12 consecutive months or more following cessation of exogenous hormonal treatment and in the absence of any alternative medical cause, as judged by the investigator. 12. Participants of childbearing potential must use a highly effective form of contraception from signing of the ICF to 14 days after the last study intervention. Highly effective birth control methods are listed below: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation): * Oral * Intravaginal (eg, NuvaRing®) * Transdermal (eg, Evra Patch™, Xulane™) Progestogen-only hormonal contraception associated with inhibition of ovulation: * Oral * Injectable (eg, Depo-Provera™) * Implantable (eg, Implanon®) Intrauterine device or intrauterine hormone-releasing system Bilateral tubal occlusion Male partner sterilization/vasectomy with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel's review of participant's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner. Note: Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), declaration of abstinence for the duration of exposure to study intervention, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Informed Consent 13. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Other Inclusion Criteria 14. Compliance: must be willing to remain at the study site as required per protocol to complete all visit assessments.
Exclusion criteria
5.2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 AUC 0-6 Hours (mL) for AS MDI Relative to Ventolin Evohaler - Non-inferiority Analysis | 0 to 6 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) | Change from baseline FEV1 measured at each time point for AS MDI and Ventolin Evohaler. Baseline FEV1 is the period specific mean of the available pre-dose values. Area Under the Curve (AUC) 0-6 hours is calculated using the trapezoidal rule and normalized by dividing by the time in hours from dosing to the last measurement included (i.e., \~ 6 hours). |
| Change From Baseline in FEV1 AUC 0-6 Hours (mL) for Ventolin Evohaler Compared With Placebo - Superiority Analysis | 0 to 6 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) | Change from baseline in FEV1 measured at each time point for Ventolin Evohaler and Placebo. Baseline FEV1 is the period specific mean of the available pre-dose values. AUC 0-6 hours is calculated using the trapezoidal rule and normalized by dividing by the time in hours from dosing to the last measurement included (i.e., \~ 6 hours). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 AUC 0-6 Hours (mL) for AS MDI Relative to Ventolin Evohaler - Equivalence Analysis | 0 to 6 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) | Change from baseline FEV1 measured at each time point for AS MDI and Ventolin Evohaler. Baseline FEV1 is the period specific mean of the available pre-dose values. AUC 0-6 hours is calculated using the trapezoidal rule and normalized by dividing by the time in hours from dosing to the last measurement included (i.e., \~ 6 hours). |
| Change From Baseline in FEV1 AUC 0-4 Hours (mL) for AS MDI Relative to Ventolin Evohaler - Non-inferiority Analysis | 0 to 4 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) | Change from baseline FEV1 measured at each time point for AS MDI and Ventolin Evohaler. Baseline FEV1 is the period specific mean of the available pre-dose values. AUC 0-4 hours is calculated using the trapezoidal rule and normalized by dividing by the time in hours from dosing to the last measurement included (i.e., \~ 4 hours). |
| Change From Baseline in FEV1 AUC 0-4 Hours (mL) for Ventolin Evohaler Compared With Placebo - Superiority Analysis | 0 to 4 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) | Change from baseline FEV1 measured at each time point for Ventolin Evohaler and Placebo. Baseline FEV1 is the period specific mean of the available pre-dose values. AUC 0-4 hours is calculated using the trapezoidal rule and normalized by dividing by the time in hours from dosing to the last measurement included (i.e., \~ 4 hours). |
| Change From Baseline in FEV1 AUC 0-4 Hours (mL) for AS MDI Relative to Ventolin Evohaler - Equivalence Analysis | 0 to 4 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) | Change from baseline FEV1 measured at each time point for AS MDI and Ventolin Evohaler. Baseline FEV1 is the period specific mean of the available pre-dose values. AUC 0-4 hours is calculated using the trapezoidal rule and normalized by dividing by the time in hours from dosing to the last measurement included (i.e., \~ 4 hours). |
| Peak Change From Baseline in FEV1 (mL) for AS MDI Relative to Ventolin Evohaler - Non-inferiority Analysis | 0 to 6 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) | Peak change from baseline in FEV1 is the difference between the maximum FEV1 value measured during the 6 hour post dose period and the baseline FEV1 for AS MDI and Ventolin Evohaler. Baseline FEV1 is the period specific mean of the available pre-dose values. |
| Peak Change From Baseline in FEV1 (mL) for Ventolin Evohaler Compared With Placebo - Superiority Analysis | 0 to 6 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) | Peak change from baseline in FEV1 is the difference between the maximum FEV1 value measured during the 6 hour post dose period and the baseline FEV1 for Ventolin Evohaler and Placebo. Baseline FEV1 is the period specific mean of the available pre-dose values. |
| Peak Change From Baseline in FEV1 (mL) for AS MDI Relative to Ventolin Evohaler - Equivalence Analysis | 0 to 6 hours (Spirometry will be obtained 60 and 30 minutes pre-dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) | Peak change from baseline in FEV1 is the difference between the maximum FEV1 value measured during the 6 hour post dose period and the baseline FEV1 for AS MDI and Ventolin Evohaler. Baseline FEV1 is the period specific mean of the available pre-dose values. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 23 sites in the United States, from February 2025 to May 2025. The study was anticipated to run for at least 15 days but not to exceed 52 days.
Pre-assignment details
A total of 164 subjects were screened for the study of which 118 subjects were randomized and treated with one of the 6 treatment sequences. Each sequence comprised all 3 treatments included in this study (i.e., AS MDI 180 μg, Ventolin Evohaler 200 μg, Placebo) in a randomized order. Remaining 46 subjects were not randomized either due to failure to meet randomization criteria, adverse event, not meeting the eligibility criteria at visit 2 or withdrawal from the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Age (years) | 43.6 Years STANDARD_DEVIATION 12.5 |
| Bronchodilator responsiveness at screening | 16.4 % STANDARD_DEVIATION 3.8 |
| Ethnicity (NIH/OMB) Ethnicity Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Ethnicity Not Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Ethnicity Unknown or Not Reported | 0 Participants |
| Lung function data at screening Post-bronchodilator FEV1 (mL) | 2793.5 FEV1 (mL) STANDARD_DEVIATION 720.6 |
| Lung function data at screening Pre-bronchodilator FEV1 (mL) | 2008.0 FEV1 (mL) STANDARD_DEVIATION 571.9 |
| Race (NIH/OMB) Race American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Race Asian | 0 Participants |
| Race (NIH/OMB) Race Black or African American | 32 Participants |
| Race (NIH/OMB) Race More than one race | 7 Participants |
| Race (NIH/OMB) Race Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Race Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) Race White | 77 Participants |
| Sex: Female, Male Sex Female | 12 Participants |
| Sex: Female, Male Sex Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 113 | 0 / 110 | 0 / 114 |
| other Total, other adverse events | 1 / 113 | 1 / 110 | 1 / 114 |
| serious Total, serious adverse events | 0 / 113 | 0 / 110 | 0 / 114 |
Outcome results
None listed