E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Asthma (an illness that causes breathing difficulty) that is not fully controlled, so that episodes of breathing difficulty are still occurring despite the use of other available treatments. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
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 assess the PK profile of AZD7594 at steady state following daily inhalations (360ug delivered dose) for 2 weeks in adolescent patients with asthma |
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E.2.2 | Secondary objectives of the trial |
To evaluate the PD (plasma cortisol, FEV1, ACQ 5) of AZD7594 following daily inhalations for 2 weeks in adolescent patients with asthma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of signed and dated informed consent prior to any study-specific procedures from patient’sparents/legal guardians is required and signed and dated informed assent from the patient. 2. Patient (male or female) must be 12 to 17 years of age inclusive, at the time of signing the informed consent/assent. 3. A minimum of 6-month documented history of asthma treated (daily or intermittently) for at least 3 months before screening (Visit 1) with either low dose ICS monotherapy or LTRA monotherapy. The patient must have used the monotherapy at least once in the 3 months prior to screening (Visit 1). 4. Pre-bronchodilator FEV1 ≥70% of the predicted normal value at screening (Visit 1) 5. An ACQ-5 (Asthma Control Questionnaire) score <1.5 at screening (Visit 1). 6. Be non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for >6 months prior to screening. 7. Body mass index (BMI) above the 5th percentile for the patient’s age and gender and a minimum weight of 30 kg at screening (Visit 1). 8. Negative pregnancy test (urine or serum) for post-menarcheal female patients at screening (Visit 1). Post-menarcheal female patients must be willing to use a highly effective method of contraception which results in a low failure rate (ie, less than 1% per year). Sexual abstinence will be accepted as an effective method of contraception, provided a discussion occurred between the subject and investigator to confirm this lifestyle. 9.Negative pregnancy test (urine or serum) for post-menarcheal female patients at baseline (Visit 4). |
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E.4 | Principal exclusion criteria |
1. Any clinically significant disease or disorder (eg, cardiovascular, pulmonary other than asthma, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment, severe obesity including weight-related health problems) which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the result of the study, or the patient’s ability to participate in the study. 2. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, at screening (Visit 1), which, in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study. 3. Prolonged QT interval corrected using Fridericia’s formula (QTcF) ≥440 msec based on ECG at screening (Visit 1) or pre-dose at Visit 4, or family history of long QT syndrome. 4. Prolonged PR interval (>180 msec for ≤16-year-old patients and >200 msec for >16-year-old patients) at screening (Visit 1) or pre-dose at Visit 4. 5. Heart rate <50 beats per minute (bpm) or >110 bpm. 6. History of or current alcohol or drug abuse (including marijuana), as judged by the Investigator. 7 Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) at screening (Visit 1). 8 Hospitalisation due to asthma exacerbation or asthma exacerbation within 1 month prior to screening (Visit 1). 9 Lower respiratory tract infection within 1 month prior to screening (Visit 1). Prior/concomitant therapy 10 Patient who, in the opinion of the Investigator, is unable to abstain from protocol-defined prohibited medications during the study. Prior/concurrent clinical study experience 11 Participation in another clinical study with an investigational drug administered in the last 3 months before Visit 1, or participation in a method development study (no drug) 1 month prior to Visit 1. Note: Participation is identified as the completion of a treatment-related visit. 12 A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the Investigator. Other exclusions 13 Inability to perform the required spirometry assessments, to use the AZD7594 inhaler or the SABA inhaler, or to undergo blood sampling. 14 Parent/legal guardian involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 15 Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 16 Previous enrolment in the present study. 17 For post-menarcheal female patients only – currently pregnant, breastfeeding, or planning to become pregnant during the study.
After the washout period, patients are eligible to enter the treatment period if none of the following exclusion criteria apply: 1 An ACQ-5 score ≥3 at Visit 4. 2 SABA use of ≥12 puffs/day for ≥3 consecutive days during the washout period. Clinical Study Protocol - 3.0 AstraZeneca AZD7594 - D3741C00012 CONFIDENTIAL AND PROPRIETARY 31 of 92 3 An asthma exacerbation that required treatment with ICSs or systemic steroids during the washout period. 4 A <70% compliance in completing asthma symptom score during the last 7 days of the washout period (ie, <5 out of 7 days with both morning and evening assessments completed). |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AZD7594 PK parameters at steady state (Day 15, pre-dose and 15 min, 30 min,2, 4, 6, 8, 12 h post-dose) to assess systemic exposure and oral clearance: Cmax,ss, Cmin,ss, Ctrough, tmax,ss, AUCĪ, AUC0-12, and CLss/F. |
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E.5.2 | Secondary end point(s) |
Pharmacodynamic (PD) endpoint: Evaluate plasma cortisol, FEV1 and ACQ-5 of AZD7594 following daily inhalations for 2 weeks.
Safety endpoint: To evaluate the tolerability and safety of inhaled AZD7594. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PD endpoint timepoint: Relative change from baseline in plasma cortisol AUEC0-12 on Day 15. Change from baseline in morning trough FEV1 on Day 15. Change from baseline in ACQ-5 on Day 15.
Safety endpoint timepoint: Incidence of AEs, vital signs, clinical laboratory parameters, physical examination, and ECG. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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
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The end of the study is defined as ‘the last visit of the last patient undergoing the study’. For this study, the last visit corresponds to the Follow-up Contact (Visit 7) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |