| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003561 |
| E.1.2 | Term | Asthma, unspecified |
| E.1.2 | System Organ Class | 100000004855 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate the contribution of budesonide and albuterol in BDA MDI 80/180 μg and 160/180 μg administered QID by comparing with mono-components (BD MDI 160 μg, AS MDI 180 μg) and placebo on lung function. |
|
| E.2.2 | Secondary objectives of the trial |
| To characterize the effect of BDA MDI 80/180 μg and 160/180 μg administered QID on bronchodilation and asthma symptoms compared to the mono components (BD MDI 160 μg, AS MDI 180 μg)and placebo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For inclusion in the study, subjects must fulfill the following criteria within the screening period:
1. Able and willing to provide written informed consent or sign age-appropriate forms; subjects below legal age of consent must have parent(s) or guardian sign the ICF before participation;
2 .Female or male aged ≥4 years at the time of informed consent. In the Czech Republic, Serbia, Slovakia, Ukraine, and Germany, only subjects aged ≥18 years will be included;
3. Diagnosis of asthma as defined by GINA criteria with a documented history of the last 6 months prior to Visit 1;
4 Receiving 1 of the following inhaled asthma medications with stable dosing for at least 30 days prior to Visit 1:
(a) Only SABA used prn
(b) Stable low-dose ICS in addition to prn use of SABA
5. Pre-bronchodilator FEV1 of ≥50 to <85% predicted normal value for adults (≥18 years of age) and ≥50 to <90% predicted normal value for subjects aged 4 to 17 years after withholding SABA ≥6 hours at Visit 1. If subject took SABA or any bronchodilator in the morning of Visit 1, either the entire visit must be rescheduled or just PFT assessment rescheduled; Subjects 4 to 17 years of age who previously failed inclusion criteria 5 due to the upper FEV1 limit will be permitted to re-screen once and will be required to meet all eligibility criteria upon re-screening.
6. Demonstrate reversibility of airflow limitation defined as a ≥15% increase in FEV1 relative to baseline after administration of Sponsor-provided SABA (Ventolin) at either Visit 1 or Visit 1a. One re-test for reversibility testing is allowed within the screening period prior to Visit 2;
7. Demonstrate acceptable spirometry performance (ie, meet American Thoracic
Society/European Respiratory Society [ATS/ERS]) acceptability/repeatability criteria; Subjects 4 to 11 years will be eligible if they provide 2 acceptable / repeatable measurements.
8. Taken Ventolin on ≥2 days out of 7 days prior to Visit 2;
9. Willing and, in the opinion of the investigator, able to adjust current asthma therapy, as required by the protocol;
10. Demonstrate acceptable metered-dose-inhaler (MDI) administration technique as assessed by the investigator;
11. Able to perform acceptable and reproducible PEF measurements as assessed by the investigator;
12. Body mass index (BMI) <40 kg/m2;
13. Willing to remain at the study site as required per protocol and complete all visit assessments;
14. Negative pregnancy test (serum at Visit 1) for female subjects of childbearing potential;
15. Women of childbearing potential and sexually active in heterosexual
relationships must agree to 1 of the following options to prevent pregnancy:
(a) Practice complete abstinence defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study treatments. Periodic abstinence is not acceptable. The reliability of
sexual abstinence needs to be evaluated in relation to the duration of the
clinical trial and the preferred and usual lifestyle of the subject. Therefore, complete abstinence is an acceptable method of contraception only if it is consistent with the preferred and usual lifestyle of the subject.
(b) If a female of childbearing potential agrees to prevent pregnancy by
using 1 of the following effective methods of birth control from the date
the ICF is signed until 2 weeks after the final dose of IP is taken:
i. Hormonal contraception (eg, oral contraceptive, contraceptive implant, or injectable hormonal contraceptive);
ii. Double-barrier birth control (eg, a combination of male condom with either cap, diaphragm, or sponge with spermicide);
iii. Maintenance of a monogamous sexual relationship with a male partner who has been surgically sterilized by vasectomy;
(c) Note: Women are considered to be of non-childbearing potential if they are physiologically incapable of becoming pregnant, including any female who is 2 years postmenopausal, or surgically sterile, defined as having a bilateral oophorectomy, hysterectomy, tubal ligation, or other permanent birth control measures. For purposes of this protocol, menopausal women are defined as women ≥50 years old that are amenorrheic for 12 consecutive months or more after cessation of all exogenous hormonal treatment. Adolescent specific recommendations: if subject is female and has reached menarche, or has reached Tanner stage 3 breast developments (even if not having reached menarche), the subject will be considered a female of child-bearing potential;
16. Male subjects who are sexually active in heterosexual relationships must be surgically sterile or agree to use a double-barrier effective method of contraception (condom with spermicide) from the first dose of randomized IP until 2 weeks after their last dose.
Male subjects must not donate sperm during their study participation period. |
|
| E.4 | Principal exclusion criteria |
Subjects must not enter the study if any of the following exclusion criteria are fulfilled within the screening period:
1. Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia);
2. Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1;
3. Chronic (≥3 weeks) use of SCS within 6 months prior to Visit 1;
4. Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab) or investigational biologic within 3 months or 5 half-lives before Visit 1, whichever is longer, or any other prohibited medication;
5. Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and marijuana);
6. Life-threatening asthma defined as any history of significant asthma episode(s) requiring admission to an intensive care unit, intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) within 5 years of Visit 1;
7. Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1;
8. Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1;
9. Hospitalizations due to asthma within 6 months prior to Visit 1;
10. Have taken ≥12 actuations per day of Sponsor-provided Ventolin during the run-in period prior to Visit 2 according to the below criteria:
(a) ≥2 days out of 14 days of run-in;
(b) ≥3 days out of 15 to 21 days of run-in;
(c) ≥4 days out of 22 or more days of run-in;
11. Unable to comply with study procedures including non-compliance with diary completion;
12. Clinically significant laboratory abnormalities, in the opinion of the investigator, or having any of the following results at Visit 1:
(a) a serum creatinine value >1.5 times the upper limit of the reference range;
(b) a serum total bilirubin value (TBL) >1.5 times the upper limit of the reference range;
(c) a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >2.5 times the upper limit of the reference range;
13. Any of the following results at Visit 1:
(a) an abnormal electrocardiogram (ECG) that is, in the investigator’s opinion, clinically significant;
(b) a QTCF interval >480 ms (subjects aged ≥12 years)/≥460 ms (subjects aged 4 to 11 years, based on the Fridericia correction where QTcF=QT/RR0.33)
14. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular (eg, congestive heart failure, known aortic aneurysm, clinicallysignificant cardiac arrhythmia, coronary heart disease), hepatic, renal, hematological, neuropsychological, endocrine (eg, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison’s disease, Cushing’s syndrome), or gastrointestinal (eg, poorly controlled peptic ulcer, gastroesophageal reflux disease) disorders. Significant is defined
as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation, or that could affect the efficacy or safety analysis if the disease/condition exacerbated during the study;
15. Cancer not in complete remission for at least 5 years before Visit 1;
16. Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1;
17. History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity
18. Significant abuse of alcohol or drugs, in the opinion of the investigator
19. A known or suspected hypersensitivity to albuterol/salbutamol, or budesonide and/or their excipients;
20. A scheduled/planned hospitalization during the study;
21. Inability to abstain from protocol-defined prohibited medications during the study;
22. Using any herbal products by inhalation or nebulizer within 2 weeks of Visit 1 and not agreeing to stop during the study duration;
23. Received a live attenuated vaccination within 7 days of Visit 1;
24. Currently pregnant or breastfeeding;
25. Study investigators, subinvestigators, coordinators, and their employees or immediate family members, or employees of the Sponsor;
26. Treatment with any investigational treatment or device in another clinical study within the last 30 days (or 5 half-lives, whichever is longer) of Visit 1
27. Currently participating in any interventional study;
28. Previously been randomized in this study or any other PT007 or PT027 clinical study. For pediatrics, see inclusion criteria 4. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Dual-primary endpoints:
• Change from baseline in FEV1 AUC0-6 hours over 12 weeks
• Change from baseline in trough FEV1 at Week 12 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Over 12 weeks and at week 12 |
|
| E.5.2 | Secondary end point(s) |
• The time to onset (defined as 15% increase in FEV1 over the pre-treatment value on Day 1), and duration of response on Day 1
• Number (%) of subjects who have an Asthma Control Questionnaire-7 (ACQ-7) score of ≥1.5 at baseline who achieve a clinically meaningful
improvement (a decrease of at least 0.5 units from baseline) in ACQ-7 at Week 12
• Trough FEV1 at Week 1 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| As defined within the end points. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 29 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Serbia |
| Ukraine |
| United States |
| Czechia |
| Germany |
| Slovakia |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS (including post study follow-up phone call) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
