Healthy
Conditions
Keywords
Safety, tolerability, healthy, pharmacokinetic, pharmacodynamic, inhaled
Brief summary
This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of AZD8848 in healthy subjects.
Detailed description
A Double-blind, Placebo-controlled, Randomised Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Inhaled Doses of AZD8848 in Healthy Subjects
Interventions
DRUGAZD8848
Single dose, oral inhalation (nebuliser solution)
DRUGPlacebo
Single dose, oral inhalation (nebuliser solution)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men or women aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture. * Women can be of childbearing potential and must have been stable on a highly effective contraceptive method for at least 3 months prior to Visit 1 (screening) and be willing to continue on the chosen contraceptive method * Male subjects should be willing to use a condom (with spermicide) to prevent pregnancy and drug exposure of a female partner and refrain from donating sperm or fathering a child from the day of the investigational product administration until 3 months * Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg * Ability to produce sputum of good enough quality for assessment of biomarkers
Exclusion criteria
* Abnormal vital signs, after 10 minutes supine rest, defined as any of the following (SBP \> 140 mmHg, Diastolic blood pressure (DBP) \> 90 mmHg, Heart rate \< 40 or \> 85 beats per minute) * Prolonged QTcF \> 450 ms or shortened QTcF \< 340 ms or family history of long QT syndrome * History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class as AZD8848 * History of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT syndrome, or sudden death) * History of asthma or allergic rhinitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Screening up to Day 13 | Summary of number of subjects who had at least one adverse event |
| Summary for Lymphocytes Laboratory Results | Baseline, Day 1, Day 2, Day 3, and Follow up (up to Day 13) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | Baseline, 24 Hours. | Smmarizes the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix |
| Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L) | On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h | — |
| Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | Baseline, 24 Hours. | Summarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix |
| Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L) | On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h | — |
| Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h | — |
Countries
United Kingdom
Participant flow
Recruitment details
There were 47 male and female subjects (6 cohorts with additional 2 cohorts) were randomized in the study.There were 6 subjects per cohort (4 subjects received AZD8848 and 2 subjects received placebo), with the exception of Cohort 3 (1.5 μg), where 3 subjects received AZD8848 and 2 subjects received placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Commercial 0.9% sodium chloride solution. | 16 |
| Cohort 1 AZD8848 0.15 μg | 4 |
| Cohort 2 AZD8848 0.5 ug | 4 |
| Cohort 3 AZD8848 1.5 μg | 3 |
| Cohort 4 AZD8848 5 μg | 4 |
| Cohort 5 AZD8848 15 μg | 4 |
| Cohort 7 AZD8848 15 μg (Multiple Inhalation) | 4 |
| Cohort 6 and 8 AZD8848 30 μg (similar investigational product administration conditions) | 8 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 | 1 | 0 | 0 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 7 | Cohort 6 and 8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 27 Years STANDARD_DEVIATION 6 | 29 Years STANDARD_DEVIATION 10 | 23 Years STANDARD_DEVIATION 3 | 24 Years STANDARD_DEVIATION 5 | 31 Years STANDARD_DEVIATION 4 | 27 Years STANDARD_DEVIATION 6 | 30 Years STANDARD_DEVIATION 9 | 31 Years STANDARD_DEVIATION 9 | 28 Years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 8 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 1 Participants | 23 Participants |
| Sex: Female, Male Male | 8 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 7 Participants | 24 Participants |
| Subject characteristics (BMI) | 24.81 kg/m² STANDARD_DEVIATION 2.71 | 27.02 kg/m² STANDARD_DEVIATION 1.94 | 23.41 kg/m² STANDARD_DEVIATION 3.5 | 25.63 kg/m² STANDARD_DEVIATION 3.16 | 24.48 kg/m² STANDARD_DEVIATION 4.46 | 25.31 kg/m² STANDARD_DEVIATION 3.47 | 24.41 kg/m² STANDARD_DEVIATION 4.87 | 25.40 kg/m² STANDARD_DEVIATION 2.37 | 25.01 kg/m² STANDARD_DEVIATION 3 |
| Subject characteristics (Height) | 170.1 cm STANDARD_DEVIATION 7.1 | 168.6 cm STANDARD_DEVIATION 1.7 | 170.5 cm STANDARD_DEVIATION 8.5 | 167.7 cm STANDARD_DEVIATION 15.5 | 166.0 cm STANDARD_DEVIATION 5 | 175.0 cm STANDARD_DEVIATION 8.3 | 169.3 cm STANDARD_DEVIATION 11.1 | 176.9 cm STANDARD_DEVIATION 8.6 | 170.9 cm STANDARD_DEVIATION 8.3 |
| Subject characteristics (Weight) | 72.1 kg STANDARD_DEVIATION 11.2 | 76.9 kg STANDARD_DEVIATION 6.7 | 68.2 kg STANDARD_DEVIATION 12.2 | 71.4 kg STANDARD_DEVIATION 5 | 67.7 kg STANDARD_DEVIATION 14.2 | 78.1 kg STANDARD_DEVIATION 16.3 | 69.4 kg STANDARD_DEVIATION 10.5 | 79.3 kg STANDARD_DEVIATION 8 | 73.3 kg STANDARD_DEVIATION 10.9 |
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 | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 16 | 2 / 4 | 1 / 4 | 0 / 3 | 3 / 4 | 1 / 4 | 2 / 4 | 4 / 8 |
| serious Total, serious adverse events | 0 / 16 | 0 / 4 | 0 / 4 | 0 / 3 | 1 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Adverse Events
Summary of number of subjects who had at least one adverse event
Time frame: Screening up to Day 13
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Adverse Events | 6 participants |
| Cohort 1 | Adverse Events | 2 participants |
| Cohort 2 | Adverse Events | 1 participants |
| Cohort 3 | Adverse Events | 0 participants |
| Cohort 4 | Adverse Events | 3 participants |
| Cohort 5 | Adverse Events | 1 participants |
| Cohort 7 | Adverse Events | 2 participants |
| Cohort 6 and 8 | Adverse Events | 4 participants |
Primary
Summary for Lymphocytes Laboratory Results
Time frame: Baseline, Day 1, Day 2, Day 3, and Follow up (up to Day 13)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary for Lymphocytes Laboratory Results | Day 1 | 2.3 cells*10^9/L | Standard Deviation 0.5 |
| Placebo | Summary for Lymphocytes Laboratory Results | Day 3 | 1.8 cells*10^9/L | Standard Deviation 0.5 |
| Placebo | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 1.7 cells*10^9/L | Standard Deviation 0.4 |
| Placebo | Summary for Lymphocytes Laboratory Results | Baseline | 1.6 cells*10^9/L | Standard Deviation 0.3 |
| Placebo | Summary for Lymphocytes Laboratory Results | Day 2 | 1.6 cells*10^9/L | Standard Deviation 0.4 |
| Cohort 1 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 2.0 cells*10^9/L | Standard Deviation 0.5 |
| Cohort 1 | Summary for Lymphocytes Laboratory Results | Day 1 | 2.1 cells*10^9/L | Standard Deviation 0.7 |
| Cohort 1 | Summary for Lymphocytes Laboratory Results | Day 3 | 2.0 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 1 | Summary for Lymphocytes Laboratory Results | Baseline | 1.7 cells*10^9/L | Standard Deviation 0.5 |
| Cohort 1 | Summary for Lymphocytes Laboratory Results | Day 2 | 2.0 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 2 | Summary for Lymphocytes Laboratory Results | Day 2 | 1.9 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 2 | Summary for Lymphocytes Laboratory Results | Baseline | 2.0 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 2 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 2.1 cells*10^9/L | Standard Deviation 0.5 |
| Cohort 2 | Summary for Lymphocytes Laboratory Results | Day 1 | 2.7 cells*10^9/L | Standard Deviation 0.7 |
| Cohort 2 | Summary for Lymphocytes Laboratory Results | Day 3 | 2.1 cells*10^9/L | Standard Deviation 0.2 |
| Cohort 3 | Summary for Lymphocytes Laboratory Results | Day 3 | 2.0 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 3 | Summary for Lymphocytes Laboratory Results | Day 2 | 2.0 cells*10^9/L | Standard Deviation 1.5 |
| Cohort 3 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 1.8 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 3 | Summary for Lymphocytes Laboratory Results | Baseline | 2.1 cells*10^9/L | Standard Deviation 0.5 |
| Cohort 3 | Summary for Lymphocytes Laboratory Results | Day 1 | 2.2 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 4 | Summary for Lymphocytes Laboratory Results | Day 3 | 2.3 cells*10^9/L | Standard Deviation 1 |
| Cohort 4 | Summary for Lymphocytes Laboratory Results | Baseline | 2.3 cells*10^9/L | Standard Deviation 0.7 |
| Cohort 4 | Summary for Lymphocytes Laboratory Results | Day 1 | 2.4 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 4 | Summary for Lymphocytes Laboratory Results | Day 2 | 2.2 cells*10^9/L | Standard Deviation 0.7 |
| Cohort 4 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 2.1 cells*10^9/L | Standard Deviation 0.8 |
| Cohort 5 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 1.9 cells*10^9/L | Standard Deviation 0.2 |
| Cohort 5 | Summary for Lymphocytes Laboratory Results | Baseline | 2.1 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 5 | Summary for Lymphocytes Laboratory Results | Day 1 | 2.4 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 5 | Summary for Lymphocytes Laboratory Results | Day 2 | 2.0 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 5 | Summary for Lymphocytes Laboratory Results | Day 3 | 2.0 cells*10^9/L | Standard Deviation 0.1 |
| Cohort 7 | Summary for Lymphocytes Laboratory Results | Day 2 | 1.4 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 7 | Summary for Lymphocytes Laboratory Results | Day 1 | 2.0 cells*10^9/L | Standard Deviation 0.4 |
| Cohort 7 | Summary for Lymphocytes Laboratory Results | Day 3 | 1.7 cells*10^9/L | Standard Deviation 0.1 |
| Cohort 7 | Summary for Lymphocytes Laboratory Results | Baseline | 1.9 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 7 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 1.7 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 6 and 8 | Summary for Lymphocytes Laboratory Results | Day 3 | 1.4 cells*10^9/L | Standard Deviation 0.2 |
| Cohort 6 and 8 | Summary for Lymphocytes Laboratory Results | Follow up (up to Day 13) | 1.5 cells*10^9/L | Standard Deviation 0.4 |
| Cohort 6 and 8 | Summary for Lymphocytes Laboratory Results | Day 1 | 1.4 cells*10^9/L | Standard Deviation 0.6 |
| Cohort 6 and 8 | Summary for Lymphocytes Laboratory Results | Baseline | 1.6 cells*10^9/L | Standard Deviation 0.3 |
| Cohort 6 and 8 | Summary for Lymphocytes Laboratory Results | Day 2 | 0.9 cells*10^9/L | Standard Deviation 0.2 |
Secondary
Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma
Smmarizes the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix
Time frame: Baseline, 24 Hours.
Population: Pharmacodynamic Population Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 0.9290 ratio | 95% Confidence Interval 10.4 |
| Cohort 1 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 0.9267 ratio | 95% Confidence Interval 107.7 |
| Cohort 2 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 0.8638 ratio | — |
| Cohort 3 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 0.9869 ratio | — |
| Cohort 4 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 1.355 ratio | — |
| Cohort 5 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 2.079 ratio | — |
| Cohort 7 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 2.120 ratio | — |
| Cohort 6 and 8 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 6.354 ratio | — |
Comparison: 24 hour Plasma95% CI: [65.76, 151.32]ANCOVA
Comparison: 24 hour Plasma95% CI: [61.21, 141.27]ANCOVA
Comparison: 24 hour Plasma95% CI: [96.11, 221.28]ANCOVA
Comparison: 24 hour Plasma95% CI: [66.42, 169.93]ANCOVA
Comparison: 24 hour plasma95% CI: [144.98, 345.35]ANCOVA
Comparison: 24 hour plasma95% CI: [150.36, 346.41]ANCOVA
Comparison: 24 hour plasma95% CI: [495.31, 944.65]ANCOVA
Secondary
Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma
Smmarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix
Time frame: Baseline, 48 Hours
Population: Pharmacodynamic Population Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 1.009 ratio | 95% Confidence Interval 10.4 |
| Cohort 1 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 0.9669 ratio | 95% Confidence Interval 107.7 |
| Cohort 2 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 0.9256 ratio | — |
| Cohort 3 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 1.134 ratio | — |
| Cohort 4 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 1.211 ratio | — |
| Cohort 5 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 1.036 ratio | — |
| Cohort 7 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 1.482 ratio | — |
| Cohort 6 and 8 | Statistical Assessment of CXCL10 Ratio-to-baseline - Plasma | 2.422 ratio | — |
Comparison: 48 hour plasma95% CI: [72.7, 126.28]ANCOVA
Comparison: 48 hour plasma95% CI: [69.53, 121]ANCOVA
Comparison: 48 hour Plasma95% CI: [82.3, 153.35]ANCOVA
Comparison: 48 hour plasma95% CI: [91.04, 158.18]ANCOVA
Comparison: 48 hour placebo95% CI: [77.02, 136.87]ANCOVA
Comparison: 48 hour plasma95% CI: [111.39, 193.62]ANCOVA
Comparison: 48 hour plasma95% CI: [193.82, 297.28]ANCOVA
Secondary
Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum
Summarize the statistical assessment comparing active CXCL10 ratio to baseline to placebo at each dose level, sampling time, and matrix
Time frame: Baseline, 24 Hours.
Population: Pharmacodynamic Population Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 1.038 ratio | 95% Confidence Interval 10.4 |
| Cohort 1 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 1.192 ratio | 95% Confidence Interval 107.7 |
| Cohort 2 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 0.8500 ratio | — |
| Cohort 3 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 0.8465 ratio | — |
| Cohort 4 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 3.160 ratio | — |
| Cohort 5 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 2.012 ratio | — |
| Cohort 7 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 4.858 ratio | — |
| Cohort 6 and 8 | Statistical Assessment of CXCL10 Ratio-to-baseline- Sputum | 11.29 ratio | — |
Comparison: 24 hour Sputum95% CI: [34.83, 378.78]ANCOVA
Comparison: 24 hour Sputum95% CI: [24.96, 268.7]ANCOVA
Comparison: 24 hour Sputum95% CI: [20.63, 322.42]ANCOVA
Comparison: 24 hour Sputum95% CI: [76.61, 1209.33]ANCOVA
Comparison: 24 hour Sputum95% CI: [59.01, 636.49]ANCOVA
Comparison: 24 hour Sputum95% CI: [142.77, 1533.92]ANCOVA
Comparison: 24 hour Sputum95% CI: [317.19, 3727.57]ANCOVA
Secondary
Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L)
Time frame: On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L) | 0.131 nmol*h/L | Geometric Coefficient of Variation 22.1 |
| Cohort 5 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L) | 0.328 nmol*h/L | Geometric Coefficient of Variation 46.2 |
| Cohort 7 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L) | 0.279 nmol*h/L | Geometric Coefficient of Variation 26.6 |
| Cohort 6 and 8 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC(0-t) (Nmol*h/L) | 0.591 nmol*h/L | Geometric Coefficient of Variation 22.3 |
90% CI: [0.65, 1.04]Regression, Linear
Secondary
Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L)
Time frame: On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L) | 0.149 nmol*h/L | Geometric Coefficient of Variation 22.9 |
| Cohort 5 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L) | 0.360 nmol*h/L | Geometric Coefficient of Variation 43.4 |
| Cohort 7 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L) | 0.312 nmol*h/L | Geometric Coefficient of Variation 26.2 |
| Cohort 6 and 8 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - AUC (Nmol*h/L) | 0.642 nmol*h/L | Geometric Coefficient of Variation 21.9 |
90% CI: [0.63, 1]Regression, Linear
Secondary
Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L)
Time frame: On Day 1 at 0min, 2min, 5min, 10min, 20min, 30min, 45min, 60min, 90min, 2h, 4h, 6h, 8h, 12h, 24h and 48h
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | 0.0362 nmol/L | Geometric Coefficient of Variation 10.3 |
| Cohort 3 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | 0.0903 nmol/L | Geometric Coefficient of Variation 40.8 |
| Cohort 4 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | 0.473 nmol/L | Geometric Coefficient of Variation 36.1 |
| Cohort 5 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | 0.963 nmol/L | Geometric Coefficient of Variation 47 |
| Cohort 7 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | 0.629 nmol/L | Geometric Coefficient of Variation 13.6 |
| Cohort 6 and 8 | Summary (Geometric Mean and GCV%) of Pharmacokinetic Parameters of Total AZ12432045 - Cmax (Nmol/L) | 1.67 nmol/L | Geometric Coefficient of Variation 18.6 |
90% CI: [0.87, 1.04]Regression, Linear