Asthma
Conditions
Keywords
AZD1402, placebo, Anticalin® protein, dry powder inhaler, inhaled corticosteroids, efficacy, safety
Brief summary
This is a randomised, placebo-controlled, double-blinded, multi-centre, 2-part study to assess the efficacy and safety of inhaled AZD1402. Part 1 will be performed in a Lead-in Cohort for each dose level to evaluate the safety and pharmacokinetics (PK) in a population with asthma controlled on medium dose inhaled corticosteroids (ICS)-long acting beta agonists (LABA) before progressing to dosing in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA in Part 2. The study will recruit participants receiving treatment with medium dose ICS with LABA for Part 1 and participants receiving treatment with medium-to-high dose ICS with LABA for Part 2 (separate inhalers or combination product). Part 2 will be initiated following evaluation of safety and PK at the relevant dose level in Part 1a. The entire study period for each participant in both Parts 1 and 2, is approximately 3.5 months; a 2-week Screening Period, a 4 week Run-in Period, 4 weeks of Treatment Period, and 4 weeks of Follow-Up Period.
Detailed description
Part 1 of the study will be randomised, double blind, placebo-controlled, and conducted in parallel for the 2 lower dose levels (Part 1a) followed by an unblinded safety review and escalation to the highest dose (Part 1b) dependent on the outcome of the safety review. Part 1a will consist of 30 participants who will be randomised 1:1:1 to receive 1 of the 2 lower AZD1402 dry power inhaler (DPI) doses (Dose 1 or Dose 2) or placebo in parallel. Part 1b will consist of 15 participants who will be randomised 2:1 to receive the highest AZD1402 DPI dose (Dose 3) or placebo. Part 1a Lead-in Cohort * AZD1402 Dose 1 * AZD1402 Dose 2 * Placebo Part 1b Lead-in Cohort * AZD1402 Dose 3 * Placebo Part 2 will be randomised, double blind, placebo controlled and will include approximately 165 participants randomised 2:1 (active to placebo) to evaluate 2 inhaled dose levels of AZD1402 versus placebo. Part 2 will be started after the unblinded safety review for Part 1a. Part 2 will include: * AZD1402 Dose 1 * AZD1402 Dose 2 * Placebo
Interventions
DRUGAZD1402
Randomised participants will receive oral inhalation of AZD1402, via DPI.
DRUGPlacebo
Randomised participants will receive oral inhalation of matching placebo via DPI.
DRUGShort acting beta agonist (SABA) (rescue medication)
In addition to study intervention, all participants will be provided with a SABA as rescue medication (eg, salbutamol/albuterol), to be used throughout the Run-in and Treatment Periods. All participants should refrain from taking a SABA as rescue medication 6 hours prior to pulmonary function tests. Dosage levels: 100 μg per nominal dose 90 μg per nominal dose pro re nata (as required) (PRN)
DRUGRun-in medications (ICS-LABA combination)
During the Run-in Period, the participants are required to maintain on their ICS-LABA dose. Controller medications (eg, ICS LABA) should remain at a stable dose and be taken after study intervention as applicable. These drugs are used as standard of care.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have a documented clinical diagnosis of asthma for ≥ 12 months before Visit 1. * Participants who are able to perform acceptable pulmonary function testing for FEV1. * Participants who are able to demonstrate the ability to use the study inhalation device properly. * Male participants must be surgically sterile or agree to use highly-effective contraceptives. * All female participants must have a negative serum pregnancy test at Screening. Female participants of non-childbearing potential, Female participants of childbearing potential must have a negative urine pregnancy test before the administration of first dose of study intervention and must agree to use a highly-effective method of birth control. * Participant is a non smoker or an ex-smoker with a total smoking history of less than 10 pack-years. * Only for Part 1: Documented treatment with medium dose ICS with LABA for at least 6 months prior to Screening. ICS and LABA must be on a stable dose for at least 3 months prior to Screening, during Screening and Run-in Periods and may be contained in a combination product or separate inhaler. No asthma exacerbations in last 12 months requiring oral or intravenous (IV) steroids or hospitalisation/ emergency room visit due to asthma. Pre-bronchodilator FEV1 ≥ 70% predicted at Screening and start of Run-in. Asthma Control Questionnaire 6 score of ≤ 1.0 at Screening and start of Run-in. * Only for Part 2: Documented evidence of asthma. Documented treatment with medium-to-high dose ICS-LABA for at least 6 months prior to Screening. ICS and LABA must be on a stable dose for at least 4 weeks prior to Screening, during Screening and Run-in Periods. If on asthma maintenance controller medications in addition to ICS-LABA, the dose of the additional controller medications must be stable for at least 4 weeks prior to Screening, during Screening and Run-in Periods. Pre bronchodilator FEV1 of 40% to 85% (inclusive) predicted at Screening and start of Run-in. Blood eosinophil count of ≥ 150 cells/μL and FeNO ≥ 25 ppb at Screening. Asthma Control Questionnaire 6 score ≥ 1.5 at Screening. Specific Randomisation Criteria at Visit 3 * For Part 1: Pre-bronchodilator FEV1 ≥ 70% predicted. At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period (from Visit 2 to Visit 3) based on daily electronic diary (e-Diary). Minimum 80% compliance with ePRO completion. Asthma Control Questionnaire 6 score of ≤ 1.0. C-reactive protein \< 5 mg/L on Day -1. * For Part 2: Pre-bronchodilator FEV1 of 40% to 85% (inclusive) predicted. Asthma Control Questionnaire 6 score of ≥ 1.5. At least 70% compliance with usual asthma controller ICS-LABA during Run-in Period from (Visit 2 to Visit 3) based on daily e-Diary. Minimum 70% compliance with ePRO completion. C-reactive protein \< 10 mg/L at Visit 2. A FeNO of ≥ 25 ppb.
Exclusion criteria
* Women who are pregnant or breastfeeding, or who are planning to become pregnant during the study. * Known or suspected hypersensitivity including anaphylaxis/anaphylactoid reaction following any biologic therapy, or known history of drug hypersensitivity to any component of the study intervention formulation. * Evidence of any active clinically important pulmonary disease other than asthma, within 5 years at screening. * History of pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts. * History or clinical suspicion of any clinically relevant or active disease or disorder. * History of severe COVID-19 infection requiring hospitalisation within the last 12 months or clinical history compatible with long COVID (symptoms beyond 12 weeks of acute infection). * Confirmed symptomatic COVID-19 infection during Screening, Run-in or prior to randomisation. * Current malignancy or history of malignancy. * Significant history of recurrent or ongoing 'dry eye'. * Diagnosis of Sjögren's syndrome. * High risk of infection suggesting abnormal immune function. * History of, or known significant infection or positivity at Screening period, including hepatitis B or C, or human immunodeficiency virus (HIV). * Evidence of active tuberculosis. * Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to Screening and during Run-in. * Clinically significant upper respiratory tract infection at Screening and during Run-in. * A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained. * Any clinically important ECG abnormalities. * Any clinically significant cardiac disease. * Uncontrolled hypertension. * History of life-threatening asthma attack or asthma attack requiring ventilation. * Part 2 only: History of 3 or more severe asthma exacerbations. * Daily rescue use of SABA ≥ 8 puffs for ≥ 3 consecutive days at any time during Run-in Period, before randomisation. * History of anaphylaxis. * Any clinically significant abnormalities in haematology. * Alanine aminotransferase or AST level ≥ 3 times the upper limit of normal (ULN), confirmed by repeated testing during Screening Period. * History of, drug or alcohol abuse within the past 2 years prior to Screening. * Planned in-patient surgery, major dental procedure or hospitalisation during the study. * Prior/Concomitant Therapy: Systemic corticosteroid use, AZD1402, marketed or investigational biologicals such as monoclonal antibodies or chimeric biomolecules, investigational nonbiologic drug within 60 days prior to Screening and during Run-in, any immunosuppressive therapy, Live or attenuated vaccine within 4 weeks of Screening and during Run-in, Receipt of COVID-19 vaccine (vaccine or booster dose) within 30 days prior to randomisation, Immunoglobulin or blood products within 4 weeks of Screening and during Run-in, Any immunotherapy within 3 months of Screening and during Run-in. * Part 1 only: Additional asthma maintenance controller medications in addition to ICS-LABA (eg, leukotriene receptor inhibitors, theophylline, LAMA, chromones) within 3 months of Screening period and during Run-in.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Events (AEs) | From Screening (Week -6) until Follow-up (Day 56) | The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated. |
| Part 2: Change From Baseline in Pre-bronchodilator FEV1 | Baseline and Week 4 | The efficacy of inhaled AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was investigated. |
| Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Baseline, Day 12, Day 16, and Day 56 | The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated. |
| Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Baseline, Day 1, Day 7, Day 14, Day 28, and Day 56 | The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated. |
| Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Baseline, Day 1, Day 7, Day 14, Day 28, and Day 56 | The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | Day 1 until Day 56 | ADA-positive samples were tested to investigate the immunogenicity of AZD1402. |
| Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Baseline, Week 4 | The efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA was further investigated. The ACQ was developed to measure asthma control. In the ACQ-6, participants were asked to recall how their asthma had been during the previous week by responding to one bronchodilation use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated a worse outcome. The mean ACQ-6 score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.75 and ≤ 1.5 indicate partly controlled asthma, and scores \> 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered clinically meaningful. |
| Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Baseline, 4 weeks | The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. Peak expiratory flow was measured by the participants at home using a peak flow meter. |
| Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Baseline, 4 weeks | The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. Peak expiratory flow was measured by the participants at home using a peak flow meter. |
| Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Baseline, 4 weeks | The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. Severity scores for asthma symptoms were recorded twice daily in the morning and evening and documented in an e-Diary. Asthma symptom scores during night-time and day-time were assessed by the participant each morning and evening according to the following scoring system: 0: You have no asthma symptoms. 1: You are aware of your asthma symptoms but you can easily tolerate the symptoms. 2: Your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep). 3: You are unable to do your normal activities (or to sleep) because of your asthma. Higher scores indicated worse outcome. |
| Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Baseline and Week 4 | The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. |
| Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Baseline, Week 4 | The effect of AZD1402 compared to placebo on airway inflammation in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was investigated. To investigate the effect of AZD1402 on airway inflammation, the measurement of FeNO was performed in accordance with ATS/ERS guidelines. Standardised conditions with regard to exhalation flow rate and duration of exhalation were followed such that plateau definition could be evaluated over a minimum of 3 seconds. |
| Part 2: Number of Participants With Adverse Events (AEs) | From Screening (Week -6) until Follow-up (Day 56) | The safety and tolerability of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was evaluated. |
| Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Baseline, Week 4 | The efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA was further investigated. The ACQ was developed to measure asthma control. In the ACQ-6, participants were asked to recall how their asthma had been during the previous week by responding to one bronchodilation use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated a worse outcome. The mean ACQ-6 score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.75 and ≤ 1.5 indicate partly controlled asthma, and scores \> 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered clinically meaningful. |
| Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 1 until Day 56 | The pharmacokinetic (PK) profile of AZD1402 was investigated. |
| Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
| Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 1 until Day 56 | The PK profile of AZD1402 was investigated. |
Countries
Australia, Canada, Germany, Hungary, Poland, South Korea, Spain, Taiwan, Ukraine, United Kingdom
Participant flow
Recruitment details
This study was conducted from 21 April 2021 to 20 July 2023 at 63 study centers in 10 countries.
Pre-assignment details
The screening period was of 2 weeks (Week -6 to Week -4) for both parts of the study. Informed Consent Form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment. Participants who met the eligibility criteria were randomized to study intervention in addition to receiving background local standard of care therapy.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: AZD1402 Dose 1 Randomised participants received oral inhalation of AZD1402 Dose 1 via DPI. | 11 |
| Part 1: AZD1402 Dose 2 Randomised participants received oral inhalation of AZD1402 Dose 2 via DPI. | 10 |
| Part 1: AZD1402 Dose 3 Randomised participants received oral inhalation of AZD1402 Dose 3 via DPI. | 13 |
| Part 1: Placebo Randomised participants received oral inhalation of matching placebo via DPI. | 16 |
| Part 2: AZD1402 Dose 1 Randomised participants received oral inhalation of AZD1402 Dose 1 via DPI. | 4 |
| Part 2: AZD1402 Dose 2 Randomised participants received oral inhalation of AZD1402 Dose 2 via DPI. | 9 |
| Part 2: Placebo Randomised participants received oral inhalation of matching placebo via DPI. | 9 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Global/country situation | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: AZD1402 Dose 1 | Total | Part 2: Placebo | Part 2: AZD1402 Dose 2 | Part 2: AZD1402 Dose 1 | Part 1: Placebo | Part 1: AZD1402 Dose 3 | Part 1: AZD1402 Dose 2 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 46.3 Years STANDARD_DEVIATION 11.5 | 52.9 Years STANDARD_DEVIATION 7.3 | 61.7 Years STANDARD_DEVIATION 6.6 | 61.3 Years STANDARD_DEVIATION 6.5 | 60.3 Years STANDARD_DEVIATION 10.2 | 50.0 Years STANDARD_DEVIATION 10.8 | 47.0 Years STANDARD_DEVIATION 17.6 | 43.6 Years STANDARD_DEVIATION 15.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 71 Participants | 9 Participants | 8 Participants | 4 Participants | 16 Participants | 13 Participants | 10 Participants |
| Sex: Female, Male Female | 7 Participants | 40 Participants | 4 Participants | 6 Participants | 2 Participants | 8 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 32 Participants | 5 Participants | 3 Participants | 2 Participants | 8 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 | 0 / 13 | 0 / 16 | 0 / 4 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 4 / 11 | 6 / 10 | 10 / 13 | 8 / 16 | 3 / 4 | 5 / 9 | 6 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 0 / 13 | 0 / 16 | 0 / 4 | 1 / 9 | 0 / 9 |
Outcome results
Primary
Part 1: Change From Baseline in FEV1 In-clinic Spirometry
The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.
Time frame: Baseline, Day 1, Day 7, Day 14, Day 28, and Day 56
Population: The safety set included all patients who were randomised and received any IP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 1 evening | -0.0338 Liters (L) | Standard Deviation 0.1794 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 morning | -0.1225 Liters (L) | Standard Deviation 0.129 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 evening | -0.0648 Liters (L) | Standard Deviation 0.1579 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 14 morning | -0.1157 Liters (L) | Standard Deviation 0.1231 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 28 morning | -0.2199 Liters (L) | Standard Deviation 0.1933 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 56 | -0.2239 Liters (L) | Standard Deviation 0.2096 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 56 | -0.1232 Liters (L) | Standard Deviation 0.1455 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 14 morning | -0.1776 Liters (L) | Standard Deviation 0.1533 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 1 evening | -0.2416 Liters (L) | Standard Deviation 0.4113 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 evening | -0.0884 Liters (L) | Standard Deviation 0.1082 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 morning | -0.2134 Liters (L) | Standard Deviation 0.1975 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 28 morning | -0.1673 Liters (L) | Standard Deviation 0.2192 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 morning | 0.0187 Liters (L) | Standard Deviation 0.1338 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 evening | 0.0430 Liters (L) | Standard Deviation 0.1613 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 14 morning | -0.0388 Liters (L) | Standard Deviation 0.2225 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 56 | -0.0830 Liters (L) | Standard Deviation 0.1802 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 28 morning | -0.0583 Liters (L) | Standard Deviation 0.1515 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 1 evening | 0.0031 Liters (L) | Standard Deviation 0.1841 |
| Part 1: Placebo | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 28 morning | -0.2050 Liters (L) | Standard Deviation 0.229 |
| Part 1: Placebo | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 56 | -0.1707 Liters (L) | Standard Deviation 0.2345 |
| Part 1: Placebo | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 morning | -0.0913 Liters (L) | Standard Deviation 0.2121 |
| Part 1: Placebo | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 14 morning | -0.0773 Liters (L) | Standard Deviation 0.1584 |
| Part 1: Placebo | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 1 evening | 0.0318 Liters (L) | Standard Deviation 0.1362 |
| Part 1: Placebo | Part 1: Change From Baseline in FEV1 In-clinic Spirometry | Day 7 evening | 0.0486 Liters (L) | Standard Deviation 0.1474 |
Primary
Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic)
The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.
Time frame: Baseline, Day 1, Day 7, Day 14, Day 28, and Day 56
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 1 evening | 12.14 Part per billion (ppb) | Geometric Coefficient of Variation 123.28 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 56 morning | 14.17 Part per billion (ppb) | Geometric Coefficient of Variation 174.36 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 28 morning | 19.07 Part per billion (ppb) | Geometric Coefficient of Variation 143.18 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 morning | 11.60 Part per billion (ppb) | Geometric Coefficient of Variation 243.83 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Average change from baseline over the treatment period | 10.23 Part per billion (ppb) | Geometric Coefficient of Variation 164.24 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 evening | 16.81 Part per billion (ppb) | Geometric Coefficient of Variation 102.28 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 14 morning | 18.17 Part per billion (ppb) | Geometric Coefficient of Variation 213.64 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 56 morning | 19.31 Part per billion (ppb) | Geometric Coefficient of Variation 62.1 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 14 morning | 23.17 Part per billion (ppb) | Geometric Coefficient of Variation 204.29 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 evening | 18.83 Part per billion (ppb) | Geometric Coefficient of Variation 230.59 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 28 morning | 16.31 Part per billion (ppb) | Geometric Coefficient of Variation 170.18 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Average change from baseline over the treatment period | 16.37 Part per billion (ppb) | Geometric Coefficient of Variation 183.76 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 morning | 23.71 Part per billion (ppb) | Geometric Coefficient of Variation 132.9 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 1 evening | 17.14 Part per billion (ppb) | Geometric Coefficient of Variation 356.42 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 14 morning | 25.06 Part per billion (ppb) | Geometric Coefficient of Variation 168.79 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 1 evening | 13.52 Part per billion (ppb) | Geometric Coefficient of Variation 162.23 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 morning | 21.55 Part per billion (ppb) | Geometric Coefficient of Variation 95.95 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 evening | 22.97 Part per billion (ppb) | Geometric Coefficient of Variation 155.86 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 28 morning | 20.06 Part per billion (ppb) | Geometric Coefficient of Variation 289.93 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 56 morning | 21.44 Part per billion (ppb) | Geometric Coefficient of Variation 212.81 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Average change from baseline over the treatment period | 20.78 Part per billion (ppb) | Geometric Coefficient of Variation 111.33 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 evening | 16.90 Part per billion (ppb) | Geometric Coefficient of Variation 140.49 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Average change from baseline over the treatment period | 14.60 Part per billion (ppb) | Geometric Coefficient of Variation 127.31 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 56 morning | 15.51 Part per billion (ppb) | Geometric Coefficient of Variation 106.64 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 7 morning | 17.61 Part per billion (ppb) | Geometric Coefficient of Variation 93.96 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 1 evening | 13.30 Part per billion (ppb) | Geometric Coefficient of Variation 150.6 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 28 morning | 16.50 Part per billion (ppb) | Geometric Coefficient of Variation 148.92 |
| Part 1: Placebo | Part 1: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) (In-clinic) | Day 14 morning | 31.32 Part per billion (ppb) | Geometric Coefficient of Variation 183.61 |
Primary
Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)
The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.
Time frame: Baseline, Day 12, Day 16, and Day 56
Population: The safety set included all patients who were randomised and received any IP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Baseline | 0.225 milligrams per deciliter (mg/dL) | Standard Deviation 0.369 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 12 | 0.167 milligrams per deciliter (mg/dL) | Standard Deviation 0.247 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 16 | 0.727 milligrams per deciliter (mg/dL) | Standard Deviation 1.906 |
| Part 1: AZD1402 Dose 1 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 56 | 0.172 milligrams per deciliter (mg/dL) | Standard Deviation 0.243 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 12 | 0.650 milligrams per deciliter (mg/dL) | Standard Deviation 1.898 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 16 | 0.166 milligrams per deciliter (mg/dL) | Standard Deviation 0.171 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 56 | 0.094 milligrams per deciliter (mg/dL) | Standard Deviation 0.095 |
| Part 1: AZD1402 Dose 2 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Baseline | 0.109 milligrams per deciliter (mg/dL) | Standard Deviation 0.08 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 16 | 1.093 milligrams per deciliter (mg/dL) | Standard Deviation 1.761 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 12 | 0.485 milligrams per deciliter (mg/dL) | Standard Deviation 0.542 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 56 | 0.119 milligrams per deciliter (mg/dL) | Standard Deviation 0.081 |
| Part 1: AZD1402 Dose 3 | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Baseline | 0.102 milligrams per deciliter (mg/dL) | Standard Deviation 0.07 |
| Part 1: Placebo | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 56 | 0.112 milligrams per deciliter (mg/dL) | Standard Deviation 0.151 |
| Part 1: Placebo | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 12 | 0.103 milligrams per deciliter (mg/dL) | Standard Deviation 0.173 |
| Part 1: Placebo | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Baseline | 0.094 milligrams per deciliter (mg/dL) | Standard Deviation 0.09 |
| Part 1: Placebo | Part 1: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) | Day 16 | 0.088 milligrams per deciliter (mg/dL) | Standard Deviation 0.091 |
Primary
Part 1: Number of Participants With Adverse Events (AEs)
The safety and tolerability of AZD1402 compared to placebo at different dose levels in adults with asthma controlled on medium dose ICS-LABA was evaluated.
Time frame: From Screening (Week -6) until Follow-up (Day 56)
Population: The safety set included all patients who were randomised and received any investigational product (IP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE | 4 Participants |
| Part 1: AZD1402 Dose 2 | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: AZD1402 Dose 2 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 1 Participants |
| Part 1: AZD1402 Dose 2 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
| Part 1: AZD1402 Dose 2 | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Part 1: AZD1402 Dose 2 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE | 6 Participants |
| Part 1: AZD1402 Dose 3 | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: AZD1402 Dose 3 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE | 10 Participants |
| Part 1: AZD1402 Dose 3 | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Part 1: AZD1402 Dose 3 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 1 Participants |
| Part 1: AZD1402 Dose 3 | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 1 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) | Any AE | 8 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
Primary
Part 2: Change From Baseline in Pre-bronchodilator FEV1
The efficacy of inhaled AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was investigated.
Time frame: Baseline and Week 4
Population: The full analysis set included all patients who were randomised and received any IP.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 | -0.0195 Liters (L) | Standard Error 0.1023 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 | 0.1529 Liters (L) | Standard Error 0.0804 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 | -0.0431 Liters (L) | Standard Error 0.0777 |
p-value: 0.82895% CI: [-0.1934, 0.2406]Mixed Models Analysis
p-value: 0.03595% CI: [0.0143, 0.3778]Mixed Models Analysis
Secondary
Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC) | NA Ratio | — |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC) | NA Ratio | — |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC) | 6.059 Ratio | Geometric Coefficient of Variation 68.5 |
| Part 1: Placebo | Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC) | NA Ratio | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Accumulation Ratio for AUCτ (Rac AUC) | NA Ratio | — |
Secondary
Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax) | 3.219 Ratio | Geometric Coefficient of Variation 121.9 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax) | 6.067 Ratio | Geometric Coefficient of Variation 78.9 |
| Part 1: Placebo | Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
Secondary
Part 1 and Part 2: Antidrug Antibodies (ADA) Titers
ADA-positive samples were tested to investigate the immunogenicity of AZD1402.
Time frame: Day 1 until Day 56
Population: The immunogenicity set included all participants in the safety set with at least one post-treatment ADA result (positive or negative). Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints. Participants in the Part 1: Placebo arm did not have any post-treatment ADA results and were excluded from analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | Treatment-induced ADA positive | 1280.0 Titer |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA positive at baseline and/or post-baseline (ADA prevalence) | 1280.0 Titer |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA persistently positive | 1280.0 Titer |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive with maximum titre > median of maximum titres | 3840.0 Titer |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive (ADA incidence) | 1280.0 Titer |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA transiently positive | NA Titer |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA persistently positive | 640.0 Titer |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | Treatment-induced ADA positive | 360.0 Titer |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive (ADA incidence) | 360.0 Titer |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA positive at baseline and/or post-baseline (ADA prevalence) | 360.0 Titer |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive with maximum titre > median of maximum titres | 1280.0 Titer |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA persistently positive | 320.0 Titer |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA positive at baseline and/or post-baseline (ADA prevalence) | 320.0 Titer |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive (ADA incidence) | 320.0 Titer |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | Treatment-induced ADA positive | 320.0 Titer |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive with maximum titre > median of maximum titres | NA Titer |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | Treatment-induced ADA positive | 240.0 Titer |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA positive at baseline and/or post-baseline (ADA prevalence) | 240.0 Titer |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive (ADA incidence) | 240.0 Titer |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive with maximum titre > median of maximum titres | NA Titer |
| Part 2: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive with maximum titre > median of maximum titres | 2560.0 Titer |
| Part 2: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | Treatment-induced ADA positive | 400 Titer |
| Part 2: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | TE-ADA positive (ADA incidence) | 400 Titer |
| Part 2: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA persistently positive | 240.0 Titer |
| Part 2: AZD1402 Dose 2 | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA positive at baseline and/or post-baseline (ADA prevalence) | 400.0 Titer |
| Part 2: Placebo | Part 1 and Part 2: Antidrug Antibodies (ADA) Titers | ADA persistently positive | 400.0 Titer |
Secondary
Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) | 21.39 Liters/hour (L/h) | Geometric Coefficient of Variation 63.3 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) | 32.33 Liters/hour (L/h) | Geometric Coefficient of Variation 94.4 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) | 37.82 Liters/hour (L/h) | Geometric Coefficient of Variation 132.7 |
| Part 1: Placebo | Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) | NA Liters/hour (L/h) | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) | NA Liters/hour (L/h) | — |
Secondary
Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 28 | 46.75 h*ng/mL | Geometric Coefficient of Variation 63.3 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 1 | 23.15 h*ng/mL | Geometric Coefficient of Variation 28.9 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 28 | 92.80 h*ng/mL | Geometric Coefficient of Variation 94.4 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 1 | 46.34 h*ng/mL | Geometric Coefficient of Variation 52.4 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 28 | 264.4 h*ng/mL | Geometric Coefficient of Variation 132.7 |
| Part 1: Placebo | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 28 | NA h*ng/mL | — |
| Part 1: Placebo | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 1 | NA h*ng/mL | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 1 | NA h*ng/mL | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Day 28 | NA h*ng/mL | — |
Secondary
Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 28 | 44.26 h*ng/mL | Geometric Coefficient of Variation 604.9 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 1 | 16.32 h*ng/mL | Geometric Coefficient of Variation 57.8 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 28 | 146.3 h*ng/mL | Geometric Coefficient of Variation 144.7 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 1 | 44.40 h*ng/mL | Geometric Coefficient of Variation 56.9 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 28 | 379.4 h*ng/mL | Geometric Coefficient of Variation 169.6 |
| Part 1: Placebo | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 28 | NA h*ng/mL | — |
| Part 1: Placebo | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 1 | NA h*ng/mL | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 1 | NA h*ng/mL | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Day 28 | NA h*ng/mL | — |
Secondary
Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 28 | 20.17 Hours (h) | Geometric Coefficient of Variation 668.7 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 1 | NA Hours (h) | — |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 28 | 7.669 Hours (h) | Geometric Coefficient of Variation 33.2 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 1 | 9.440 Hours (h) | Geometric Coefficient of Variation 49.4 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 28 | 8.546 Hours (h) | Geometric Coefficient of Variation 34.5 |
| Part 1: Placebo | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 28 | NA Hours (h) | — |
| Part 1: Placebo | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 1 | NA Hours (h) | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 1 | NA Hours (h) | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Day 28 | NA Hours (h) | — |
Secondary
Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax)
The pharmacokinetic (PK) profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 28 | 3.986 Nanograms Per Milliliter (ng/mL) | Geometric Coefficient of Variation 68.9 |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 1 | NA Nanograms Per Milliliter (ng/mL) | — |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 28 | 10.46 Nanograms Per Milliliter (ng/mL) | Geometric Coefficient of Variation 103 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 1 | 2.745 Nanograms Per Milliliter (ng/mL) | Geometric Coefficient of Variation 43.2 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 1 | 5.864 Nanograms Per Milliliter (ng/mL) | Geometric Coefficient of Variation 50.2 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 28 | 30.97 Nanograms Per Milliliter (ng/mL) | Geometric Coefficient of Variation 124.7 |
| Part 1: Placebo | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 1 | NA Nanograms Per Milliliter (ng/mL) | — |
| Part 1: Placebo | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 28 | NA Nanograms Per Milliliter (ng/mL) | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 28 | NA Nanograms Per Milliliter (ng/mL) | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Maximum Observed Serum (Peak) Drug Concentration (Cmax) | Day 1 | NA Nanograms Per Milliliter (ng/mL) | — |
Secondary
Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 28 | 2.854 ng/mL | Geometric Coefficient of Variation 66.3 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 1 | 1.702 ng/mL | Geometric Coefficient of Variation 30 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 28 | 5.145 ng/mL | Geometric Coefficient of Variation 96.8 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 1 | 2.917 ng/mL | Geometric Coefficient of Variation 53.6 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 28 | 13.83 ng/mL | Geometric Coefficient of Variation 144.2 |
| Part 1: Placebo | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 28 | NA ng/mL | — |
| Part 1: Placebo | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 1 | NA ng/mL | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 1 | NA ng/mL | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Observed Lowest Drug Concentration Reached Before the Next Dose is Administered (Pre-dose) (Ctrough) | Day 28 | NA ng/mL | — |
Secondary
Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 28 | 0.03437 1/hour | Geometric Coefficient of Variation 668.7 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 1 | NA 1/hour | — |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 28 | 0.09040 1/hour | Geometric Coefficient of Variation 33.2 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 1 | 0.07343 1/hour | Geometric Coefficient of Variation 49.4 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 28 | 0.08111 1/hour | Geometric Coefficient of Variation 34.5 |
| Part 1: Placebo | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 28 | NA 1/hour | — |
| Part 1: Placebo | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 1 | NA 1/hour | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 1 | NA 1/hour | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) | Day 28 | NA 1/hour | — |
Secondary
Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 1 | NA Hours |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 28 | 11.99 Hours |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 1 | 8.000 Hours |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 28 | 17.83 Hours |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 1 | 11.47 Hours |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 28 | 23.94 Hours |
| Part 1: Placebo | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 28 | NA Hours |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 28 | NA Hours |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Time of Last Observed (Quantifiable) Concentration (Tlast) | Day 1 | NA Hours |
Secondary
Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 28 | 3.025 Hours |
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 1 | NA Hours |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 1 | 3.000 Hours |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 28 | 3.000 Hours |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 1 | 4.017 Hours |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 28 | 3.950 Hours |
| Part 1: Placebo | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 28 | NA Hours |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 28 | NA Hours |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) | Day 1 | NA Hours |
Secondary
Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F)
The PK profile of AZD1402 was investigated.
Time frame: Day 1 until Day 56
Population: The PK set included all patients in the safety set who had detectable PK data and with no major protocol deviations considered to impact on the analysis of PK data. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F) | 622.5 Liters | Geometric Coefficient of Variation 1007.5 |
| Part 1: AZD1402 Dose 2 | Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F) | 322.9 Liters | Geometric Coefficient of Variation 109.7 |
| Part 1: AZD1402 Dose 3 | Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F) | 466.3 Liters | Geometric Coefficient of Variation 172 |
| Part 1: Placebo | Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F) | NA Liters | — |
| Part 2: AZD1402 Dose 1 | Part 1 and Part 2: Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F) | NA Liters | — |
Secondary
Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period
The efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA was further investigated. The ACQ was developed to measure asthma control. In the ACQ-6, participants were asked to recall how their asthma had been during the previous week by responding to one bronchodilation use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated a worse outcome. The mean ACQ-6 score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.75 and ≤ 1.5 indicate partly controlled asthma, and scores \> 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered clinically meaningful.
Time frame: Baseline, Week 4
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Change from baseline at Week 4 | -0.80 Score on scale | Standard Deviation 0.37 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Average change from baseline over treatment period | -0.75 Score on scale | Standard Deviation 0.56 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Change from baseline at Week 4 | -0.71 Score on scale | Standard Deviation 0.68 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Average change from baseline over treatment period | -0.78 Score on scale | Standard Deviation 0.33 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Change from baseline at Week 4 | -0.56 Score on scale | Standard Deviation 0.75 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) at Week 4 and Average Over the Treatment Period | Average change from baseline over treatment period | -0.56 Score on scale | Standard Deviation 0.66 |
Secondary
Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period
The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. Peak expiratory flow was measured by the participants at home using a peak flow meter.
Time frame: Baseline, 4 weeks
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Change from baseline at Week 4 | 18.68 Liters/minute (L/m) | Standard Deviation 3.94 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Average change from baseline over the treatment period | 14.20 Liters/minute (L/m) | Standard Deviation 10.37 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Change from baseline at Week 4 | -15.81 Liters/minute (L/m) | Standard Deviation 28.63 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Average change from baseline over the treatment period | -7.75 Liters/minute (L/m) | Standard Deviation 25.79 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Change from baseline at Week 4 | 0.89 Liters/minute (L/m) | Standard Deviation 30.22 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Average Evening PEF Over the Treatment Period | Average change from baseline over the treatment period | 1.87 Liters/minute (L/m) | Standard Deviation 19.27 |
Secondary
Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period
The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. Peak expiratory flow was measured by the participants at home using a peak flow meter.
Time frame: Baseline, 4 weeks
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Change from baseline at Week 4 | 23.73 Liters/minute (L/m) | Standard Deviation 15.24 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Average change from baseline over the treatment period | 20.67 Liters/minute (L/m) | Standard Deviation 8.58 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Change from baseline at Week 4 | 19.88 Liters/minute (L/m) | Standard Deviation 47.38 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Average change from baseline over the treatment period | 21.40 Liters/minute (L/m) | Standard Deviation 37.83 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Change from baseline at Week 4 | -2.53 Liters/minute (L/m) | Standard Deviation 26.69 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the Treatment Period | Average change from baseline over the treatment period | -5.54 Liters/minute (L/m) | Standard Deviation 24.17 |
Secondary
Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period
The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated. Severity scores for asthma symptoms were recorded twice daily in the morning and evening and documented in an e-Diary. Asthma symptom scores during night-time and day-time were assessed by the participant each morning and evening according to the following scoring system: 0: You have no asthma symptoms. 1: You are aware of your asthma symptoms but you can easily tolerate the symptoms. 2: Your asthma is causing you enough discomfort to cause problems with normal activities (or with sleep). 3: You are unable to do your normal activities (or to sleep) because of your asthma. Higher scores indicated worse outcome.
Time frame: Baseline, 4 weeks
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Change from baseline at Week 4 | -0.23 Score on scale | Standard Deviation 0.26 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Average change from baseline over the treatment period | -0.10 Score on scale | Standard Deviation 0.27 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Change from baseline at Week 4 | 0.07 Score on scale | Standard Deviation 0.26 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Average change from baseline over the treatment period | 0.02 Score on scale | Standard Deviation 0.22 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Change from baseline at Week 4 | -0.04 Score on scale | Standard Deviation 0.37 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Daily Average Asthma Symptom Score (AM/PM) Over the Treatment Period | Average change from baseline over the treatment period | -0.07 Score on scale | Standard Deviation 0.32 |
Secondary
Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period
The effect of AZD1402 compared to placebo on airway inflammation in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was investigated. To investigate the effect of AZD1402 on airway inflammation, the measurement of FeNO was performed in accordance with ATS/ERS guidelines. Standardised conditions with regard to exhalation flow rate and duration of exhalation were followed such that plateau definition could be evaluated over a minimum of 3 seconds.
Time frame: Baseline, Week 4
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Change from baseline at Week 4 | 39.77 Parts per billion (ppb) | Geometric Coefficient of Variation 55.03 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Average change from baseline over the treatment period | 32.02 Parts per billion (ppb) | Geometric Coefficient of Variation 153.61 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Change from baseline at Week 4 | 28.76 Parts per billion (ppb) | Geometric Coefficient of Variation 91.99 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Average change from baseline over the treatment period | 14.16 Parts per billion (ppb) | Geometric Coefficient of Variation 343.96 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Change from baseline at Week 4 | 31.20 Parts per billion (ppb) | Geometric Coefficient of Variation 122.5 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in FeNO (In-clinic) at Week 4 and Average Over the Treatment Period | Average change from baseline over the treatment period | 27.45 Parts per billion (ppb) | Geometric Coefficient of Variation 102.83 |
p-value: 0.20295% CI: [-71.11, 31.72]Mixed Models Analysis
p-value: 0.59695% CI: [-55.57, 60.96]Mixed Models Analysis
Secondary
Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period
The efficacy of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was further investigated.
Time frame: Baseline and Week 4
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 1 | 0.0233 Liters (L) | Standard Error 0.0526 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 2 | 0.0028 Liters (L) | Standard Error 0.0618 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 3 | 0.0160 Liters (L) | Standard Error 0.114 |
| Part 1: AZD1402 Dose 1 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 4 | 0.0095 Liters (L) | Standard Error 0.1085 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 4 | 0.1500 Liters (L) | Standard Error 0.1898 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 1 | 0.1408 Liters (L) | Standard Error 0.1679 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 3 | 0.0431 Liters (L) | Standard Error 0.1676 |
| Part 1: AZD1402 Dose 2 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 2 | 0.0866 Liters (L) | Standard Error 0.1607 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 4 | -0.0252 Liters (L) | Standard Error 0.1754 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 2 | 0.1671 Liters (L) | Standard Error 0.3323 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 3 | 0.1099 Liters (L) | Standard Error 0.1583 |
| Part 1: AZD1402 Dose 3 | Part 2: Change From Baseline in Pre-bronchodilator FEV1 Average Over the 4-week Treatment Period | Week 1 | 0.0101 Liters (L) | Standard Error 0.1094 |
Secondary
Part 2: Number of Participants With Adverse Events (AEs)
The safety and tolerability of AZD1402 compared to placebo in adults with asthma uncontrolled on medium-to-high dose ICS-LABA was evaluated.
Time frame: From Screening (Week -6) until Follow-up (Day 56)
Population: The safety set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 2: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE | 3 Participants |
| Part 1: AZD1402 Dose 1 | Part 2: Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Part 1: AZD1402 Dose 1 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE | 5 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Number of Participants With Adverse Events (AEs) | Any SAE | 1 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 0 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE leading to withdrawal from study | 0 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of IP | 0 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Number of Participants With Adverse Events (AEs) | Any AE | 6 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
Secondary
Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4
The efficacy of AZD1402 compared to placebo in adults with asthma who are uncontrolled on medium-to-high dose ICS-LABA was further investigated. The ACQ was developed to measure asthma control. In the ACQ-6, participants were asked to recall how their asthma had been during the previous week by responding to one bronchodilation use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). Higher scores indicated a worse outcome. The mean ACQ-6 score is the mean of the responses. Mean scores of ≤ 0.75 indicate well-controlled asthma, scores between 0.75 and ≤ 1.5 indicate partly controlled asthma, and scores \> 1.5 indicate not well-controlled asthma. Individual changes of at least 0.5 are considered clinically meaningful.
Time frame: Baseline, Week 4
Population: The full analysis set included all patients who were randomised and received any IP. Here, 'number of participants analyzed' specifies participants evaluated for this outcome measure at specific timepoints.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: AZD1402 Dose 1 | Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Responder | 3 Participants |
| Part 1: AZD1402 Dose 1 | Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Non-responder | 1 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Responder | 7 Participants |
| Part 1: AZD1402 Dose 2 | Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Non-responder | 2 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Responder | 3 Participants |
| Part 1: AZD1402 Dose 3 | Part 2: Participants With a Decrease in ACQ 6 Score of ≥ 0.5 From Baseline to Week 4 | Non-responder | 6 Participants |