Trial Outcomes & Findings for A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants (NCT NCT03276052)
NCT ID: NCT03276052
Last Updated: 2023-12-11
Results Overview
Characterization of Cmax, taken directly from the individual concentration-time curve after single dose or multiple dose.
COMPLETED
PHASE1
20 participants
Day 1 and Day 9
2023-12-11
Participant Flow
The study was conducted at one study centre in China between 14 October 2021 to 26 November 2021.
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.
Participant milestones
| Measure |
Aclidinium Bromide 400 μg
Healthy Chinese participants received aclidinium bromide 400 μg.
|
|---|---|
|
Overall Study
STARTED
|
43
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
23
|
Reasons for withdrawal
| Measure |
Aclidinium Bromide 400 μg
Healthy Chinese participants received aclidinium bromide 400 μg.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Screening failure (non-fulfilment of inclusion/exclusion criteria)
|
18
|
Baseline Characteristics
A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants
Baseline characteristics by cohort
| Measure |
Aclidinium Bromide 400 μg
n=20 Participants
Healthy Chinese participants received aclidinium bromide 400 μg.
|
|---|---|
|
Age, Continuous
|
27.15 years
STANDARD_DEVIATION 5.20 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian/Chinese
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of Cmax, taken directly from the individual concentration-time curve after single dose or multiple dose.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
LAS34850 (inactive acid metabolite)
|
3831 pg/mL
Geometric Coefficient of Variation 24.99
|
4891 pg/mL
Geometric Coefficient of Variation 16.52
|
|
Maximum Observed Plasma Concentration (Cmax)
LAS34823 (inactive alcohol metabolite)
|
164.0 pg/mL
Geometric Coefficient of Variation 45.05
|
294.1 pg/mL
Geometric Coefficient of Variation 39.93
|
|
Maximum Observed Plasma Concentration (Cmax)
Aclidinium bromide
|
238.6 pg/mL
Geometric Coefficient of Variation 51.67
|
341.3 pg/mL
Geometric Coefficient of Variation 40.24
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of Tmax, taken directly from the individual concentration-time curve after single dose or multiple dose.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Time to Reach Maximum Observed Concentration (Tmax)
Aclidinium bromide
|
0.08 Hour
Interval 0.08 to 0.1
|
0.08 Hour
Interval 0.08 to 0.1
|
|
Time to Reach Maximum Observed Concentration (Tmax)
LAS34850 (inactive acid metabolite)
|
3.00 Hour
Interval 2.0 to 3.0
|
2.50 Hour
Interval 1.5 to 3.0
|
|
Time to Reach Maximum Observed Concentration (Tmax)
LAS34823 (inactive alcohol metabolite)
|
0.08 Hour
Interval 0.08 to 0.5
|
0.08 Hour
Interval 0.08 to 0.5
|
PRIMARY outcome
Timeframe: Day 1Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Area Under the Concentration-time From Zero to Infinity (AUCinf)
Aclidinium bromide
|
266.1 h*pg/mL
Geometric Coefficient of Variation 59.15
|
—
|
|
Area Under the Concentration-time From Zero to Infinity (AUCinf)
LAS34850 (inactive acid metabolite)
|
29970 h*pg/mL
Geometric Coefficient of Variation 17.63
|
—
|
|
Area Under the Concentration-time From Zero to Infinity (AUCinf)
LAS34823 (inactive alcohol metabolite)
|
684.4 h*pg/mL
Geometric Coefficient of Variation 48.04
|
—
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Area Under the Concentration-time From Time 0 to 12 Hours Post-dose [AUC(0-12)]
Aclidinium bromide
|
167.1 h*pg/mL
Geometric Coefficient of Variation 40.19
|
357.8 h*pg/mL
Geometric Coefficient of Variation 32.28
|
|
Area Under the Concentration-time From Time 0 to 12 Hours Post-dose [AUC(0-12)]
LAS34850 (inactive acid metabolite)
|
22730 h*pg/mL
Geometric Coefficient of Variation 18.64
|
33910 h*pg/mL
Geometric Coefficient of Variation 15.33
|
|
Area Under the Concentration-time From Time 0 to 12 Hours Post-dose [AUC(0-12)]
LAS34823 (inactive alcohol metabolite)
|
438.1 h*pg/mL
Geometric Coefficient of Variation 37.26
|
1031 h*pg/mL
Geometric Coefficient of Variation 25.56
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of AUClast, taken directly from the individual concentration-time curve after single dose or multiple dose.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Area Under the Concentration-time From Zero to the Last Quantifiable Concentration (AUClast)
Aclidinium bromide
|
208.9 h*pg/mL
Geometric Coefficient of Variation 57.23
|
609.4 h*pg/mL
Geometric Coefficient of Variation 36.49
|
|
Area Under the Concentration-time From Zero to the Last Quantifiable Concentration (AUClast)
LAS34850 (inactive acid metabolite)
|
29010 h*pg/mL
Geometric Coefficient of Variation 18.02
|
50370 h*pg/mL
Geometric Coefficient of Variation 16.78
|
|
Area Under the Concentration-time From Zero to the Last Quantifiable Concentration (AUClast)
LAS34823 (inactive alcohol metabolite)
|
550.4 h*pg/mL
Geometric Coefficient of Variation 54.05
|
1849 h*pg/mL
Geometric Coefficient of Variation 25.49
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of t½λz, of aclidinium bromide and its metabolites after single and multiple doses of aclidinium bromide in healthy Chinese participants.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Half-life Associated With Terminal Slope of a Semi-logarithmic Concentration-time Curve (t½λz)
Aclidinium bromide
|
13.50 Hour
Geometric Coefficient of Variation 91.55
|
21.42 Hour
Geometric Coefficient of Variation 25.63
|
|
Half-life Associated With Terminal Slope of a Semi-logarithmic Concentration-time Curve (t½λz)
LAS34850 (inactive acid metabolite)
|
8.322 Hour
Geometric Coefficient of Variation 26.83
|
12.68 Hour
Geometric Coefficient of Variation 18.98
|
|
Half-life Associated With Terminal Slope of a Semi-logarithmic Concentration-time Curve (t½λz)
LAS34823 (inactive alcohol metabolite)
|
9.964 Hour
Geometric Coefficient of Variation 42.98
|
17.66 Hour
Geometric Coefficient of Variation 12.35
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of CL/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Apparent Total Body Clearance From Plasma After Extravascular Administration (CL/F)
|
1503 Liter/hour
Geometric Coefficient of Variation 59.15
|
1118 Liter/hour
Geometric Coefficient of Variation 32.28
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of Vz/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Volume of Distribution (Apparent) Following Extravascular Administration Based on Terminal Phase (Vz/F)
|
29280 Liter
Geometric Coefficient of Variation 45.53
|
34550 Liter
Geometric Coefficient of Variation 40.89
|
PRIMARY outcome
Timeframe: Day 1Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of MRTinf, of aclidinium bromide after single dose of aclidinium bromide in healthy Chinese participants.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf)
|
13.45 Hour
Geometric Coefficient of Variation 95.18
|
—
|
PRIMARY outcome
Timeframe: Day 1 and Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of Cmin, taken directly from the individual concentration-time curve after single dose or multiple dose.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
n=20 Participants
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Minimum Observed Drug Concentration (Cmin)
LAS34850 (inactive acid metabolite)
|
647.8 pg/mL
Geometric Coefficient of Variation 20.84
|
1223 pg/mL
Geometric Coefficient of Variation 19.34
|
|
Minimum Observed Drug Concentration (Cmin)
LAS34823 (inactive alcohol metabolite)
|
14.82 pg/mL
Geometric Coefficient of Variation 31.53
|
43.03 pg/mL
Geometric Coefficient of Variation 28.55
|
|
Minimum Observed Drug Concentration (Cmin)
Aclidinium bromide
|
3.251 pg/mL
Geometric Coefficient of Variation 56.25
|
11.55 pg/mL
Geometric Coefficient of Variation 41.22
|
PRIMARY outcome
Timeframe: Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
Characterization of Cavg, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Average Drug Concentration Over a Dosing Interval (Cavg)
Aclidinium bromide
|
29.82 pg/mL
Geometric Coefficient of Variation 32.28
|
—
|
|
Average Drug Concentration Over a Dosing Interval (Cavg)
LAS34850 (inactive acid metabolite)
|
2826 pg/mL
Geometric Coefficient of Variation 15.33
|
—
|
|
Average Drug Concentration Over a Dosing Interval (Cavg)
LAS34823 (inactive alcohol metabolite)
|
85.95 pg/mL
Geometric Coefficient of Variation 25.56
|
—
|
PRIMARY outcome
Timeframe: Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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).
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Accumulation Ratio for Cmax [Rac(Cmax)]
Aclidinium bromide
|
1.431 Ratio
Geometric Coefficient of Variation 44.18
|
—
|
|
Accumulation Ratio for Cmax [Rac(Cmax)]
LAS34850 (inactive acid metabolite)
|
1.277 Ratio
Geometric Coefficient of Variation 20.40
|
—
|
|
Accumulation Ratio for Cmax [Rac(Cmax)]
LAS34823 (inactive alcohol metabolite)
|
1.794 Ratio
Geometric Coefficient of Variation 45.61
|
—
|
PRIMARY outcome
Timeframe: Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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)
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Accumulation Ratio for Cmin (Rac[Cmin])
Aclidinium bromide
|
3.554 Ratio
Geometric Coefficient of Variation 50.32
|
—
|
|
Accumulation Ratio for Cmin (Rac[Cmin])
LAS34850 (inactive acid metabolite)
|
1.888 Ratio
Geometric Coefficient of Variation 22.90
|
—
|
|
Accumulation Ratio for Cmin (Rac[Cmin])
LAS34823 (inactive alcohol metabolite)
|
2.903 Ratio
Geometric Coefficient of Variation 37.70
|
—
|
PRIMARY outcome
Timeframe: Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Accumulation Ratio for AUCτ (Rac[AUC])
LAS34823 (inactive alcohol metabolite)
|
2.354 Ratio
Geometric Coefficient of Variation 40.94
|
—
|
|
Accumulation Ratio for AUCτ (Rac[AUC])
Aclidinium bromide
|
2.141 Ratio
Geometric Coefficient of Variation 37.64
|
—
|
|
Accumulation Ratio for AUCτ (Rac[AUC])
LAS34850 (inactive acid metabolite)
|
1.492 Ratio
Geometric Coefficient of Variation 16.84
|
—
|
PRIMARY outcome
Timeframe: Day 9Population: The PK analysis set consisted of all participants in the safety analysis set who received at least 1 dose of aclidinium bromide.
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.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Fluctuation Index During a Dosing Interval (%Fluc)
Aclidinium bromide
|
1102 Percentage
Geometric Coefficient of Variation 34.70
|
—
|
|
Fluctuation Index During a Dosing Interval (%Fluc)
LAS34850 (inactive acid metabolite)
|
128.9 Percentage
Geometric Coefficient of Variation 14.90
|
—
|
|
Fluctuation Index During a Dosing Interval (%Fluc)
LAS34823 (inactive alcohol metabolite)
|
289.2 Percentage
Geometric Coefficient of Variation 35.31
|
—
|
SECONDARY outcome
Timeframe: From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)Population: 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.
The safety, and tolerability of aclidinium bromide 400 μg BID after single and multiple dose administration in healthy Chinese participants was evaluated.
Outcome measures
| Measure |
Single Dose (Day 1)
n=20 Participants
Healthy Chinese participants received a single dose of aclidinium bromide 400 μg on Day 1.
|
Multiple Dose (Day 9)
Healthy Chinese participants received twice daily doses of aclidinium bromide from Day 5 to Day 8, followed by a single dose on Day 9.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Any AE
|
5 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs)
Any AE with outcome = death
|
0 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs)
Any SAE (including events with outcome = death)
|
0 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs)
Any AE leading to discontinuation of IP
|
0 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs)
Any AE of special interest
|
1 Participants
|
—
|
Adverse Events
Aclidinium Bromide 400 μg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Aclidinium Bromide 400 μg
n=20 participants at risk
Healthy Chinese participants received aclidinium bromide 400 μg.
|
|---|---|
|
Nervous system disorders
Syncope
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
|
Cardiac disorders
Atrial escape rhythm
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
|
Vascular disorders
Orthostatic hypotension
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
1/20 • Number of events 1 • From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
- Publication restrictions are in place
Restriction type: OTHER