Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| M-AS273-01 | Other Identifier | Clinical Trial Protocol Code |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A Phase I, single centre, open-label study to investigate the pharmacokinetics (PK), safety and tolerability of single and multiple twice daily doses of inhaled Aclidinium Bromide in healthy Chinese male and female subjects.
Screening will be performed within 21 days of dosing on Day 1. Eligible participants will be admitted to the trial center on Day -1.
Subjects will receive single dose on Day 1, twice daily regimen is from D5 to D8, and only morning dose will be given on Day 9.
During treatment period, from Day 1 through Day 11 at Visit 2, safety measurements (blood pressure, 12-lead ECG; and AE/SAE monitoring) and blood samples for PK assessments will be collected at predetermined time points.
Clinical laboratory tests (haematology, serum biochemistry and urinalysis) will be performed under fasting conditions at Day -1 at Visit 2.
A follow-up visit will be performed on Day 15.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aclidinium Bromide 400 μg | Experimental | One inhalation from the 400 μg Aclidinium Bromide inhaler. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aclidinium Bromide 400 μg | Drug | Aclidinium Bromide 400 μg BID inhalation powder. One oral inhalation via Genuair® dry powder inhaler (DPI) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Characterization of Cmax, taken directly from the individual concentration-time curve after single dose or multiple dose. | Day 1 and Day 9 |
| Time to Reach Maximum Observed Concentration (Tmax) | Characterization of Tmax, taken directly from the individual concentration-time curve after single dose or multiple dose. | Day 1 and Day 9 |
| Area Under the Concentration-time From Zero to Infinity (AUCinf) | Characterization of AUCinf (single dose). Area under the concentration time curve from time zero extrapolated to infinity. AUC(0-∞) is estimated by AUC(last) + Clast/λz where Clast is the last observed quantifiable concentration. | Day 1 |
| Area Under the Concentration-time From Time 0 to 12 Hours Post-dose [AUC(0-12)] | The AUC(0-12) of aclidinium bromide and its metabolites after single dose of aclidinium bromide in healthy Chinese participants is investigated. Description of the AUC(0-12), partial area under the concentration- time curve in the dose interval after single dose or multiple dose. | Day 1 and Day 9 |
| Area Under the Concentration-time From Zero to the Last Quantifiable Concentration (AUClast) | Characterization of AUClast, taken directly from the individual concentration-time curve after single dose or multiple dose. | Day 1 and Day 9 |
| Half-life Associated With Terminal Slope of a Semi-logarithmic Concentration-time Curve (t½λz) | Characterization of t½λz, of aclidinium bromide and its metabolites after single and multiple doses of aclidinium bromide in healthy Chinese participants. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | The safety, and tolerability of aclidinium bromide 400 μg BID after single and multiple dose administration in healthy Chinese participants was evaluated. | From Screening (Day -21 to Day -2) until the follow-up visit (Day 15) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Weimin Li | West China Hostial, Sichuan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chengdu | 610000 | China |
Not provided
| Label | URL |
|---|---|
| CSR Synopsis | View source |
| Protocol | View source |
Not provided
The Screening period was of 21 days before randomization. Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
The study was conducted at one study centre in China between 14 October 2021 to 26 November 2021.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Aclidinium Bromide 400 μg | Healthy Chinese participants received aclidinium bromide 400 μg. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety analysis set included all participants who received at least 1 dose of IP and for whom any safety post-dose data were available.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Aclidinium Bromide 400 μg | Healthy Chinese participants received aclidinium bromide 400 μg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) | Characterization of Cmax, taken directly from the individual concentration-time curve after single dose or multiple dose. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Day 1 and Day 9 |
|
From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aclidinium Bromide 400 μg | Healthy Chinese participants received aclidinium bromide 400 μg. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Nervous system disorders | MedDRA 24.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Head | AstraZeneca | +187724094 79 | information.center@astrazeneca.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 5, 2021 | Mar 2, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 27, 2021 | Mar 2, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C542859 | aclidinium bromide |
Not provided
Not provided
Not provided
Single and Multiple Dose (Twice-Daily)
Not provided
Not provided
Not provided
Not provided
| Day 1 and Day 9 |
| Apparent Total Body Clearance From Plasma After Extravascular Administration (CL/F) | Characterization of CL/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants. | Day 1 and Day 9 |
| Volume of Distribution (Apparent) Following Extravascular Administration Based on Terminal Phase (Vz/F) | Characterization of Vz/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants. | Day 1 and Day 9 |
| Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) | Characterization of MRTinf, of aclidinium bromide after single dose of aclidinium bromide in healthy Chinese participants. | Day 1 |
| Minimum Observed Drug Concentration (Cmin) | Characterization of Cmin, taken directly from the individual concentration-time curve after single dose or multiple dose. | Day 1 and Day 9 |
| Average Drug Concentration Over a Dosing Interval (Cavg) | Characterization of Cavg, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. | Day 9 |
| Accumulation Ratio for Cmax [Rac(Cmax)] | Characterization of Rac(Cmax), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(Cmax) is caculated as a ratio for Cmax estimated as (ratio of Css,max on Day 9/Cmax on Day 1). | Day 9 |
| Accumulation Ratio for Cmin (Rac[Cmin]) | Characterization of Rac(Cmin), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(Cmin) is calculated as ratio for Cmin estimated as (ratio of Css, Cmin on Day 9/ Cmin on Day 1) | Day 9 |
| Accumulation Ratio for AUCτ (Rac[AUC]) | Characterization of Rac(AUC), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(AUC), calculated as ratio of AUC(0-12) on day 9 and AUC0-12 on Day 1. | Day 9 |
| Fluctuation Index During a Dosing Interval (%Fluc) | Characterization of %Fluc, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. The %Fluc index is estimated as 100 x (Cmax- Cmin)/Cav. | Day 9 |
| Statistical Analysis Plan (SAP) | View source |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
| Primary | Time to Reach Maximum Observed Concentration (Tmax) | Characterization of Tmax, taken directly from the individual concentration-time curve after single dose or multiple dose. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Median | Full Range | Hour | Day 1 and Day 9 |
|
|
|
| Primary | Area Under the Concentration-time From Zero to Infinity (AUCinf) | Characterization of AUCinf (single dose). Area under the concentration time curve from time zero extrapolated to infinity. AUC(0-∞) is estimated by AUC(last) + Clast/λz where Clast is the last observed quantifiable concentration. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 |
|
|
|
| Primary | Area Under the Concentration-time From Time 0 to 12 Hours Post-dose [AUC(0-12)] | The AUC(0-12) of aclidinium bromide and its metabolites after single dose of aclidinium bromide in healthy Chinese participants is investigated. Description of the AUC(0-12), partial area under the concentration- time curve in the dose interval after single dose or multiple dose. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 and Day 9 |
|
|
|
| Primary | Area Under the Concentration-time From Zero to the Last Quantifiable Concentration (AUClast) | Characterization of AUClast, taken directly from the individual concentration-time curve after single dose or multiple dose. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 and Day 9 |
|
|
|
| Primary | Half-life Associated With Terminal Slope of a Semi-logarithmic Concentration-time Curve (t½λz) | Characterization of t½λz, of aclidinium bromide and its metabolites after single and multiple doses of aclidinium bromide in healthy Chinese participants. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | Day 1 and Day 9 |
|
|
|
| Primary | Apparent Total Body Clearance From Plasma After Extravascular Administration (CL/F) | Characterization of CL/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter/hour | Day 1 and Day 9 |
|
|
|
| Primary | Volume of Distribution (Apparent) Following Extravascular Administration Based on Terminal Phase (Vz/F) | Characterization of Vz/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | Day 1 and Day 9 |
|
|
|
| Primary | Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf) | Characterization of MRTinf, of aclidinium bromide after single dose of aclidinium bromide in healthy Chinese participants. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour | Day 1 |
|
|
|
| Primary | Minimum Observed Drug Concentration (Cmin) | Characterization of Cmin, taken directly from the individual concentration-time curve after single dose or multiple dose. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Day 1 and Day 9 |
|
|
|
| Primary | Average Drug Concentration Over a Dosing Interval (Cavg) | Characterization of Cavg, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Day 9 |
|
|
|
| Primary | Accumulation Ratio for Cmax [Rac(Cmax)] | Characterization of Rac(Cmax), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(Cmax) is caculated as a ratio for Cmax estimated as (ratio of Css,max on Day 9/Cmax on Day 1). | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 9 |
|
|
|
| Primary | Accumulation Ratio for Cmin (Rac[Cmin]) | Characterization of Rac(Cmin), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(Cmin) is calculated as ratio for Cmin estimated as (ratio of Css, Cmin on Day 9/ Cmin on Day 1) | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 9 |
|
|
|
| Primary | Accumulation Ratio for AUCτ (Rac[AUC]) | Characterization of Rac(AUC), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(AUC), calculated as ratio of AUC(0-12) on day 9 and AUC0-12 on Day 1. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Day 9 |
|
|
|
| Primary | Fluctuation Index During a Dosing Interval (%Fluc) | Characterization of %Fluc, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. The %Fluc index is estimated as 100 x (Cmax- Cmin)/Cav. | The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage | Day 9 |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) | The safety, and tolerability of aclidinium bromide 400 μg BID after single and multiple dose administration in healthy Chinese participants was evaluated. | The safety analysis set included all participants who received at least 1 dose of IP and for whom any safety post-dose data were available. | Posted | Number | Participants | From Screening (Day -21 to Day -2) until the follow-up visit (Day 15) |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 5 |
| 20 |
| Atrial escape rhythm | Cardiac disorders | MedDRA 24.1 | Non-systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 24.1 | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 24.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 24.1 | Non-systematic Assessment |
|
This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
| LAS34823 (inactive alcohol metabolite) |
|
|
| LAS34823 (inactive alcohol metabolite) |
|
| LAS34823 (inactive alcohol metabolite) |
|
| LAS34823 (inactive alcohol metabolite) |
|
| LAS34823 (inactive alcohol metabolite) |
|
|
|
|
|
|
| Title | Measurements |
|---|---|
|
| Any AE leading to discontinuation of IP |
|
| Any AE of special interest |
|