A Phase I, Open-Label, Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide in Healthy Chinese Participants

NCT03276052 | Completed Phase 1 Results

• 2 other identifiers: D6572C00002M-AS273-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Pharmacokinetics

Outcome Measures

Primary Outcomes (15)

• 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.

  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

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs)

  From Screening (Day -21 to Day -2) until the follow-up visit (Day 15)

Study Arms (1)

Aclidinium Bromide 400 μg

EXPERIMENTAL

One inhalation from the 400 μg Aclidinium Bromide inhaler.

Drug: Aclidinium Bromide 400 μg

Interventions

Aclidinium Bromide 400 μg DRUG

Aclidinium Bromide 400 μg BID inhalation powder. One oral inhalation via Genuair® dry powder inhaler (DPI)

Aclidinium Bromide 400 μg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to communicate with medical team and staff, willing to participate in the trial, willing to give written informed consent, and comply with the trial restrictions.
• Healthy subjects: Chinese men or non-pregnant, non-lactating women, 18 through 45 years old at Visit 1 (Screening).
• Have a body mass index (BMI) ≥19 kg/m2 and ≤ 26 kg/m2
• Resting heart rate ≥ 50 beats per minute (bpm) and ≤ 100 bpm at Visit 1 (Screening) and at admission to the unit on Day -1 at Visit 2.
• Non-smoker (never smoked or has not smoked within 2 years prior to the first dose of investigational product \[IP\]).
• Demonstrate satisfactory technique in the use of the DPI at screening.

You may not qualify if:

• History of any significant drug allergy or hypersensitivity to aclidinium bromide or other muscarinic antagonists.
• Have abnormal and clinically significant results on the physical examination, medical history, serum biochemistry, haematology, or urinalysis at Visit 1 (Screening).
• Sustained resting systolic blood pressure ≥ 140 or ≤ 90 mmHg and resting diastolic blood pressure ≥ 90 or ≤ 50 mmHg at Visit 1 (Screening) or Day -1 at Visit 2.
• Electrocardiogram (ECG) showing corrected QT interval (QTc) using Fridericia's correction (QTcF) ≥ 450 msec for male participants and ≥460 msec for female participants as indicated in the centralised reading report assessed at Screening (Visit 1).
• Have a history of alcohol or substance abuse within the previous 5 years, as reported by the participants.
• Positive results for drugs of abuse at Visit 1 (Screening).
• Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody and/or human immunodeficiency virus (HIV) antibodies at Visit 1 (Screening).
• Use of any medication within 2 weeks or within the equivalent time of 5 half-lives of taking the last dose (whichever is longer) before the first dose of IP, or hormonal drug products and traditional Chinese medicines within 30 days before the first dose of IP.
• Have consumed caffeine or any grapefruit-containing products within 48 hours or alcohol within 72 hours before Day -1.
• Participation in any other clinical investigation using an experimental drug requiring repeated blood or plasma draws within 60 days of Day 1 at Visit 2.
• Have participated in a blood/plasma donation or blood loss greater than 400 mL within 90 days, or greater than 200 mL within 30 days prior to screening (Visit 1).
• Recent history of a disease or condition that would result in any residual upper respiratory airways/lung inflammatory process or residual limited lung function at the time of Day 1 at Visit 2.
• History of confirmed COVID-19 infection.
• Have any gastrointestinal, hepatic, or renal condition that might affect the absorption, distribution, biotransformation, or excretion of aclidinium bromide.
• Inability to be venipunctured or tolerate venous access as determined by the PI or designee.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Chengdu, 610000, China

Location

Related Links

• CSR Synopsis
• Protocol
• Statistical Analysis Plan (SAP)

MeSH Terms

Interventions

aclidinium bromide

Results Point of Contact

• Title: Global Clinical Head
• Organization: AstraZeneca

information.center@astrazeneca.com

+187724094 79

Study Officials

• Weimin Li

  West China Hostial, Sichuan University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single and Multiple Dose (Twice-Daily)

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 8, 2017
• Study Start: October 14, 2021
• Primary Completion: November 26, 2021
• Study Completion: November 26, 2021
• Last Updated: December 11, 2023
• Results First Posted: December 11, 2023

Record last verified: 2023-02

Locations

CN (1)