A Blinded, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of an Oral Suspension of AZD6793 Following Single and Multiple Ascending Doses in Healthy Subjects, an Open-label Study to Assess the Relative Bioavailability and Food Effect of a Tablet Formulation of AZD6793 in Healthy Subjects and a Blinded, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of a Tablet Formulation of AZD6793 in Patients With Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 93
- 试验地点
- 1
- 主要终点
- Part 1 (SAD): Number of participants with abnormal findings in vital signs (supine Blood Pressure (BP), pulse, respiratory rate, peripheral oxygen saturation (SpO2) and oral body temperature)
研究概览
简要总结
The purpose of the study is to assess the safety and tolerability of AZD6793 suspension following oral administration of Single Ascending Dose (SAD) [Part 1] and Multiple Ascending Dose (MAD) [Part 2] in healthy participants.
Additionally, the study will include Part 3 (bioavailability and food effect cohort) to assess the relative oral bioavailability between test formulation and oral suspension (reference formulation) as well as the effect of a high fat high calorie (HFHC) meal on the PK of AZD6793 test formulation, in comparison to fasting conditions, after a single oral dose of AZD6793 in healthy participants.
Part 4 of the study (Chronic Obstructive Pulmonary Disease [COPD] cohort) is intended to evaluate AZD6793 safety, tolerability, and PK profile for the first time in participants with moderate to severe COPD.
Part 1 (SAD), Part 2 (MAD) and Part 3 (Bioavailability and food effect cohort) have been completed. Although it was planned that 5 cohorts would be included in Part 1, only 4 cohorts (32 participants) were included. Part 3 of the study was concluded with 13 healthy participants.
详细描述
Parts 1, 2, and 3 were conducted in a single center and Part 4 is conducted in 2 centers.
Part 1 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2)
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 (the day before IMP administration [Day 1]) until at least 72 hours after IMP administration. Participants will then be discharged on Day 4 if in good health and after all samples have been collected. Depending on the emerging data, the length of the stay at the Clinical Unit may be changed.
- A Follow-up Visit within 6 ± 1 days after the IMP dose (this visit may be done later if indicated, for example, if emerging PK data indicates a longer AZD6793 half-life than was predicted).
Part 2 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2).
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 (the day before first IMP administration [Day 1]) until Day 10. participants will receive a single dose of IMP in the morning on Day 1. After a washout of at least 48 hours (depending on PK data from Part 1), participants will be dosed twice daily (12 hours apart) from Day 3 through Day 7. Participants will receive the last dose of IMP in the morning of Day 8. Participants will then be discharged on Day 10 if in good health and after all samples have been collected.
- A Follow-up Visit within 6 ± 1 days after the last IMP dose (this visit may be done later if indicated, for example, if emerging PK data indicates a longer AZD6793 half-life than was predicted).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parts 1,2 and 3:
- •Healthy male or female participants aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture
- •Females must have a negative pregnancy test must not be lactating and must be either (a) non-childbearing potential, confirmed by post-menopausal defined as amenorrhea for at least 12 months; documentation of irreversible surgical sterilisation or (b) childbearing potential, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile (Must agree to use, with their partner, an approved method of highly effective contraception).
- •Male participants and their female partners of childbearing potential must be willing to use highly effective contraception measures and male participants must refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.
- •Have a BMI between 18 and 30 kg/m2 inclusive and weigh at least 50 kg, at the Screening Visit.
- •Male and/or female participants, who have moderate to severe COPD, and aged 40 through 80 years inclusive.
- •BMI between 18 to 44.9 kg/m2 at Screening
- •Documented history of COPD with a post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator FEV1 ≥ 30% and < 80% predicted at Screening
- •Documented stable inhaled treatment regimen of dual therapy or triple therapy for ≥ 3 months prior to Screening.
- •Clinically stable and free from an Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the opinion of the Investigator for at least 35 days prior to Day 1
- •Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of :
- •Non-childbearing potential confirmed at screening
- •If considered of childbearing potential, must agree to use with their partner an approved method of highly effective contraception.
- •Male participants and their female partners of childbearing potential must be willing to use highly effective contraception measures and must refrain from donating sperm or fathering a child from first day of dosing until 3 months after last IMP dose.
排除标准
- •Parts 1,2 and 3:
- •History or presence of gastrointestinal, hepatic, renal, pancreatic disease or acute disease in these organs.
- •History of chronic haematologic disease.
- •Diagnosis or history of immunodeficiency or increased susceptibility to severe infection, or a clinically significant infection
- •Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- •Positive or indeterminate QuantiFERON® Tuberculosis (TB) test at screening.
- •Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results
- •Any positive result on Screening for serum Hepatitis B surface antigen (HBsAg), hepatitis C antibody and Human immunodeficiency virus (HIV).
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting Electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG.
- •Known or suspected history of alcohol and drug abuse in the last year.
- •Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the previous 3 months.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD
- •Excessive intake of caffeine containing drinks or food
- •Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- •Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life
- •Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
- •Parts 2 and 3 only: Participants who have previously received AZD
- •Concurrent enrolment in another clinical study involving an investigational treatment
- •Participants unable to perform reproducible spirometry according to American Thoracic Society/ European Respiratory Society [ATS/ERS] criteria at Screening
- •Any active medical condition or other reason (at Screening, Day -1, and pre-dose) that would interfere with evaluation of the investigational product or interpretation of participant safety or study results, any other clinically relevant abnormal findings on physical examination or laboratory testing at Screening
- •Positive or indeterminate QuantiFERON® TB test at Screening. Indeterminate results may be repeated during Screening.
- •Major surgery within 8 weeks prior to Screening
- •Donation of blood or blood products in excess of 500 mL within 3 months prior to Screening
- •History or current diagnosis of cancer, history of an underlying condition that predisposes the participant to infections, known history of severe reaction to any medication, history of allogeneic bone marrow transplant and history of viral, bacterial or fungal infections within 4 weeks prior to randomisation
- •Receiving any immunotherapy or immunosuppressive therapy other than corticosteroids within 6 months of randomisation
- •Participants taking metformin during Screening or at any time during the study
- •Any participant with active hepatitis or Human immunodeficiency virus (HIV)
- •History or presence of vitiligo or significant (in the opinion of the Investigator) skin depigmentation for any cause including drugs
- •History of clinically significant chronic/active haematology disease
研究组 & 干预措施
Part 1 (SAD): Cohort 1
6 Healthy participants will receive a single oral dose A of AZD6793 and 2 healthy participants will receive placebo
干预措施: AZD6793 (Drug)
Part 1 (SAD): Cohort 1
6 Healthy participants will receive a single oral dose A of AZD6793 and 2 healthy participants will receive placebo
干预措施: Placebo (Drug)
Part 1 (SAD): Cohort 2
6 Healthy participants will receive a single oral dose B of AZD6793 and 2 healthy participants will receive placebo
干预措施: AZD6793 (Drug)
Part 1 (SAD): Cohort 2
6 Healthy participants will receive a single oral dose B of AZD6793 and 2 healthy participants will receive placebo
干预措施: Placebo (Drug)
Part 1 (SAD): Cohort 3
6 Healthy participants will receive a single oral dose C of AZD6793 and 2 healthy participants will receive placebo
干预措施: AZD6793 (Drug)
Part 1 (SAD): Cohort 3
6 Healthy participants will receive a single oral dose C of AZD6793 and 2 healthy participants will receive placebo
干预措施: Placebo (Drug)
Part 1 (SAD): Cohort 4
6 Healthy participants will receive a single oral dose D of AZD6793 and 2 healthy participants will receive placebo
干预措施: AZD6793 (Drug)
Part 1 (SAD): Cohort 4
6 Healthy participants will receive a single oral dose D of AZD6793 and 2 healthy participants will receive placebo
干预措施: Placebo (Drug)
Part 1 (SAD): Cohort 5
6 Healthy participants will receive a single oral dose E of AZD6793 and 2 healthy participants will receive placebo
干预措施: AZD6793 (Drug)
Part 1 (SAD): Cohort 5
6 Healthy participants will receive a single oral dose E of AZD6793 and 2 healthy participants will receive placebo
干预措施: Placebo (Drug)
Part 2 (MAD): Cohort 1
6 Healthy participants will receive dose W of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: AZD6793 (Drug)
Part 2 (MAD): Cohort 1
6 Healthy participants will receive dose W of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: Placebo (Drug)
Part 2 (MAD): Cohort 2
6 Healthy participants will receive dose X of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: AZD6793 (Drug)
Part 2 (MAD): Cohort 2
6 Healthy participants will receive dose X of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: Placebo (Drug)
Part 2 (MAD): Cohort 3
6 Healthy participants will receive dose Y of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: AZD6793 (Drug)
Part 2 (MAD): Cohort 3
6 Healthy participants will receive dose Y of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: Placebo (Drug)
Part 2 (MAD) : Cohort 4
6 Healthy participants will receive dose Z of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: AZD6793 (Drug)
Part 2 (MAD) : Cohort 4
6 Healthy participants will receive dose Z of AZD6793 and 2 healthy participants will receive placebo once daily on Day 1 and 8 and twice daily on Day 3 to Day 7
干预措施: Placebo (Drug)
Part 3: Treatment sequence 1
Participants will receive a single oral dose of test formulation AZD6793 in fasted state, test formulation AZD6793 in fed state following reference formulation AZD6793 in fasted state once on Day 1 of each treatment period.
干预措施: AZD6793 (Drug)
Part 3: Treatment sequence 2
Participants will receive a single oral dose of test formulation AZD6793 in fed state, reference formulation AZD6793 in fasted state following test formulation AZD6793 in fasted state once on Day 1 of each treatment period.
干预措施: AZD6793 (Drug)
Part 3: Treatment sequence 3
Participants will receive a single oral dose of reference formulation AZD6793 in fasted state, test formulation AZD6793 in fasted state following test formulation AZD6793 in fed state once on Day 1 of each treatment period.
干预措施: AZD6793 (Drug)
Part 4 (COPD): Cohort 1
10 participants with COPD will receive AZD6793 once daily and 5 participants with COPD will receive placebo
干预措施: AZD6793 (Drug)
Part 4 (COPD): Cohort 1
10 participants with COPD will receive AZD6793 once daily and 5 participants with COPD will receive placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1 (SAD): Number of participants with abnormal findings in vital signs (supine Blood Pressure (BP), pulse, respiratory rate, peripheral oxygen saturation (SpO2) and oral body temperature)
时间窗: From screening, Treatment Day 1 to Day 4 up to Follow up visit (Day 6±1)
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 4 (COPD): Number of participants with abnormal findings in 12 Lead electrocardiogram (ECG)
时间窗: From screening up to Follow up visit (Day 34±2)
Safety and tolerability of AZD6793 following oral administration repeated up to 28 days (at least 26 days) in COPD participants.
Part 2 (MAD): Number of participants with abnormal findings in 12 Lead electrocardiogram (ECG)
时间窗: From screening, Treatment Day -1 to Day 10 up to Follow up visit (Day 14±1)
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 2 (MAD): Number of participants with abnormal findings in Telemetry
时间窗: Day -1 to Day 2 and Day 8 to Day 10
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 1 (SAD): Number of participants with abnormal findings in Physical examinations
时间窗: From screening, Treatment Day -1 to 4 and follow up visit
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 3 (Bioavailability): Area under plasma concentration-time curve from zero to infinity [AUCinf]
时间窗: Day 1 to Day 3
Evaluating the relative oral bioavailability between the test formulation and the reference formulation after a single oral dose of AZD6793 in healthy participants.
Part 4 (COPD): Number of participants with abnormal findings in vital signs (supine Blood Pressure (BP), pulse, respiratory rate, peripheral oxygen saturation (SpO2) and oral body temperature)
时间窗: From screening up to Follow up visit (Day 34±2)
Safety and tolerability of AZD6793 following oral administration repeated up to 28 days (at least 26 days) in COPD participants.
Part 1 (SAD): Number of participants with adverse events
时间窗: From screening up to Follow up visit (Day 6±1)
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 2 (MAD): Number of participants with abnormal findings in vital signs (supine Blood Pressure (BP), pulse, respiratory rate, peripheral oxygen saturation (SpO2) and oral body temperature)
时间窗: From screening, Treatment Day -1 to Day 10 up to Follow up visit (Day 14±1)
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 1 (SAD): Number of participants with abnormal findings in 12 Lead electrocardiogram (ECG)
时间窗: From screening, Treatment Day -1 to Day 4 up to Follow up visit (Day 6±1)
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 3 (Bioavailability): Maximum observed plasma (peak) drug concentration [Cmax]
时间窗: Day 1 to Day 3
Evaluating the relative oral bioavailability between the test formulation and the reference formulation after a single oral dose of AZD6793 in healthy participants.
Part 4 (COPD): Number of participants with abnormal findings in Physical examinations
时间窗: From screening, Treatment Day -1, 1, 14, 28 and follow up visit (34±2)
Safety and tolerability of AZD6793 following oral administration repeated up to 28 days (at least 26 days) in COPD participants.
Part 4 (COPD): Number of participants with abnormal findings in Laboratory assessments (haematology, clinical chemistry, coagulation tests, and urinalysis)
时间窗: From screening up to Follow up visit (Day 34±2)
Safety and tolerability of AZD6793 following oral administration repeated up to 28 days (at least 26 days) in COPD participants.
Part 2 (MAD): Number of participants with adverse events
时间窗: From screening up to Follow up visit (Day 14±1)
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 1 (SAD): Number of participants with abnormal findings in 12 Lead Digital electrocardiogram (dECG)
时间窗: Day 1 to Day 3
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 1 (SAD): Number of participants with abnormal findings in Telemetry
时间窗: Day -1 to Day 3
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 2 (MAD): Number of participants with abnormal findings in Physical examinations
时间窗: From screening, Treatment Day -1 to 10 and follow up visit
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 1 (SAD): Number of participants with abnormal findings in Laboratory assessments (haematology, serum clinical chemistry, and urinalysis)
时间窗: From screening, Treatment Day -1, Day 2, Day 4 and Follow up visit (Day 6±1)
Safety and tolerability of AZD6793 following oral administration of SAD in healthy participants.
Part 3 (Food effect): AUCinf of AZD6793
时间窗: Day 1 to Day 3
Investigating the effect of a high fat high calorie (HFHC) meal compared to fasting conditions, on the PK of AZD6793 after a single oral dose in healthy participants.
Part 2 (MAD): Number of participants with abnormal findings in 12 Lead Digital electrocardiogram (dECG)
时间窗: Day 1 to Day 3, Day 5, Day 8 to Day 10
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 2 (MAD): Number of participants with abnormal findings in Laboratory assessments (haematology, serum clinical chemistry, and urinalysis)
时间窗: From screening, Treatment Day -1 to Day 10 up to Follow up visit (Day 14±1)
Safety and tolerability of AZD6793 following oral administration of MAD in healthy participants.
Part 3 (Food effect): Cmax of AZD6793
时间窗: Day 1 to Day 3
Investigating the effect of a high fat high calorie (HFHC) meal compared to fasting conditions, on the PK of AZD6793 after a single oral dose in healthy participants.
Part 4 (COPD): Number of participants with adverse events
时间窗: From screening up to Follow up visit (Day 34±2)
Safety and tolerability of AZD6793 following oral administration repeated up to 28 days (at least 26 days) in COPD participants.
次要结局
- Part 1 (SAD): Maximum observed plasma (peak) drug concentration (Cmax)(Day 1 to Day 3)
- Part 1 (SAD): Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve ( t½λz)(Day 1 to Day 3)
- Part 1 (SAD): Area under the plasma concentration time curve from time zero extrapolated to infinity divided by the dose administered (Dose normalised AUCinf)(Day 1 to Day 3)
- Part 2 (MAD): Time to reach peak or maximum observed concentration or response following drug administration (tmax)(Day 1 to Day 10)
- Part 1 (SAD): Time to reach peak or maximum observed concentration or response following drug administration (tmax)(Day 1 to Day 3)
- Part 1 (SAD): Maximum observed plasma (peak) drug concentration divided by the dose administered (Dose normalised Cmax).(Day 1 to Day 3)
- Part 2 (MAD): Temporal change parameter (TCP) assessed in urine(Day 1 and Day 8)
- Part 1 (SAD): Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)(Day 1 to Day 3)
- Part 1 (SAD): Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Day 1 to Day 3)
- Part 2 (MAD): Maximum observed plasma (peak) drug concentration (Cmax)(Day 1 to Day 10)
- Part 2 (MAD): Partial area under the plasma concentration time curve from time 0 to time 24 (AUC(0-24))(Day 1 to Day 10)
- Part 2 (MAD): Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)(Day 1 to Day 10)
- Part 2 (MAD): Area under plasma concentration time curve in the dosing interval t (AUCt)(Day 1 to Day 10)
- Part 1 (SAD): Partial area under the plasma concentration time curve from time 0 to time 12 (AUC(0-12))(Day 1 to Day 3)
- Part 1 (SAD): Area under plasma concentration time curve from zero to infinity (AUCinf)(Day 1 to Day 3)
- Part 2 (MAD): Concentration at the end of the dosing interval (Ctrough)(Day 1 to Day 10)
- Part 2 (MAD): Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Day 1 to Day 10)
- Part 3 (Bioavailability): Vz/F of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Food effect): λz of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 1 (SAD): Terminal rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz)(Day 1 to Day 3)
- Part 1 (SAD): Partial area under the plasma concentration time curve from time 0 to time 24 (AUC(0-24))(Day 1 to Day 3)
- Part 1 (SAD): Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F)(Day 1 to Day 3)
- Part 1 (SAD): Area under the plasma concentration time curve from time zero to time of last quantifiable analyte concentration divided by the dose administered (Dose normalised AUClast)(Day 1 to Day 3)
- Part 2 (MAD): Terminal rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz)(Day 1 to Day 10)
- Part 2 (MAD): Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F)(Day 1 to Day 10)
- Part 2 (MAD): Area under the plasma concentration time curve from time zero to time of last quantifiable analyte concentration divided by the dose administered (Dose normalised AUClast)(Day 1 to Day 10)
- Part 2 (MAD): Ratio of the area under the curve (Rac AUC)(Day 1 to Day 10)
- Part 3 (Bioavailability): tmax of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): λz of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability) :Relative bioavailability calculated as test AUC/reference AUC [Frel AUC](Day 1 to Day 3)
- Part 2 (MAD): Area under the plasma concentration-time curve from time zero to the dosing interval t concentration divided by the dose administered (Dose normalised AUCt)(Day 1 to Day 10)
- Part 2 (MAD): Cumulative amount of unchanged drug excreted into urine (Aeinf)(Day 1 and Day 8)
- Part 2 (MAD): Renal clearance of drug from plasma (CLR) assessed in urine(Day 1 and Day 8)
- Part 3 (Bioavailability): Cmax of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): AUClast of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): CL/F of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Food effect): AUClast of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect): tmax of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 4 (COPD): Time to reach peak or maximum observed concentration or response following drug administration (tmax)(Day 1 to Day 28)
- Part 4 (COPD): Terminal rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz)(Day 1 to Day 28)
- Part 2 (MAD): Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve ( t½λz)(Day 1 to Day 10)
- Part 2 (MAD): Area under plasma concentration time curve from zero to infinity (AUCinf)(Day 1 to Day 10)
- Part 2 (MAD): Maximum observed plasma (peak) drug concentration divided by the dose administered (Dose normalised Cmax)(Day 1 to Day 10)
- Part 2 (MAD): Accumulation ratio based on Cmax (Rac Cmax)(Day 1 to Day 10)
- Part 2 (MAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1 t2)](Day 1 and Day 8)
- Part 3 (Bioavailability): t½λz of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): AUC(0-12) of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): AUC(0-24) of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): AUCinf of AZD6793 (test Vs reference formulation)(Day 1 to Day 3)
- Part 3 (Bioavailability): Relative bioavailability calculated as test Cmax/reference Cmax [Frel Cmax](Day 1 to Day 3)
- Part 3 (Food effect): Cmax of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect): t½λz of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect): AUC(0-12) of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect): Frel Cmax of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect): Vz/F of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect) :Frel AUC of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 4 (COPD): Maximum observed plasma (peak) drug concentration (Cmax)(Day 1 to Day 28)
- Part 4 (COPD): Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)(Day 1 to Day 28)
- Part 4 (COPD): Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Day 1 to Day 28)
- Part 3 (Food effect): AUC(0-24) of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 3 (Food effect): AUCinf of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 4 (COPD): Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve ( t½λz)(Day 1 to Day 28)
- Part 3 (Food effect): CL/F of AZD6793 (under fasted and fed state)(Day 1 to Day 3)
- Part 4 (COPD): Concentration at the end of the dosing interval (Ctrough)(Day 1 to Day 28)
- Part 4 (COPD): Partial area under the plasma concentration time curve from time 0 to time 12 (AUC(0-12))(Day 1 to Day 28)
- Part 4 (COPD): Partial area under the plasma concentration time curve from time 0 to time 24 (AUC(0-24))(Day 1 to Day 28)
- Part 4 (COPD): Ratio of the area under the curve (Rac AUC)(Day 1 to Day 28)
- Part 4 (COPD): Accumulation ratio based on Cmax (Rac Cmax)(Day 1 to Day 28)
- Part 4 (COPD): Temporal change parameter (TCP) assessed in urine(Day 1 and Day 8)
- Part 4 (COPD): Area under plasma concentration time curve from zero to infinity (AUCinf)(Day 1 to Day 28)
- Part 4 (COPD): Area under plasma concentration time curve in the dosing interval t (AUCt)(Day 1 to Day 28)
- Part 4 (COPD): Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F)(Day 1 to Day 28)