Pulmonary Disease, Chronic ObstructivePhase 2NCT03276078
Pharmacokinetics, Safety and Tolerability of Twice-Daily Aclidinium Bromide/Formoterol Fumarate Fixed Dose Combination in Chinese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
A Phase 2 study testing Aclidinium Bromide/Formoterol Fumarate 400/12μg BID in people with Pulmonary Disease, Chronic Obstructive, run by AstraZeneca at 1 site in China.
Trial summary
A Phase IIa, open-label, repeat-dose trial to investigate the pharmacokinetics (PK), safety and tolerability of single and multiple twice daily doses of inhaled Aclidinium Bromide/Formoterol Fumarate 400/12 μg in 20 Chinese male and female patients with stable moderate to severe COPD. Read more about this study
- Who is it for?
- Ages 40 to 130 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Aclidinium Bromide/Formoterol Fumarate 400/12μg BID
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 23 Nov 2017to 12 Jun 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 procedures and restrictions.
- Chinese men or non-pregnant, non-lactating women, aged ≥40 years old at Visit 1 (Screening).
- Patients with a diagnosis of COPD (GOLD guidelines) for a period of at least 6 months prior to Visit 1 (screening).
- Current or former smokers with a smoking history of ≥10 pack-years.
- Patients with moderate to severe stable COPD (Stage II or Stage III, according to GOLD Guidelines) at Visit 1: post-bronchodilator FEV1 ≥30% and <80% and post-bronchodilator FEV1/FVC <70%.
- Must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria at Visit 1 (Screening).
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff) or patients employed by or relatives of the employees of the site or sponsor.
- Previous enrolment or randomisation in the present study.
- History or current diagnosis of asthma.
- Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period.
- Patients hospitalized for COPD exacerbation (an emergency room visit for longer than 24 hours will be considered a hospitalization) within 3 months prior to screening and during the run-in period.
- Use of long-term oxygen therapy ≥15 hours per day.
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- Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, inhaled medication, or any component thereof.
- Patients with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients with symptomatic nonstable prostatic hypertrophy.
- Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypothyroidism or hyperthyroidism, hypokalaemia, hyperadrenergic state, or uncontrolled or untreated hypertension.
- Clinically significant cardiovascular conditions.
- Patient with resting systolic blood pressure ≥160 mmHg, a resting diastolic blood pressure ≥100 mmHg, or a resting heart rate ≤50 bpm or ≥100 bpm at Visit 1 (Screening) or/and at Visit 2 (Day -1 to Day 7).
- Have a body mass index (BMI) ≥40 kg/m2
- Electrocardiogram (ECG) at Screening or Day -1 showing corrected QT interval (QTc) using Fridericia's correction (QTcF) >470 msec.
- Patients with clinically relevant abnormalities in the results of the laboratory tests, ECG parameters (other than QTcF), or in the physical examination at Visit 1, except those related to COPD.
- Positive results for drugs of abuse in the urine at Visit 1 (Screening).
- Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody and/or human immunodeficiency virus (HIV) I antibodies at Visit 1 (Screening).
- History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer.
- Any other serious or uncontrolled physical or mental condition/disease.
- Patient with a history (within 2 years prior to Visit 1 [Screening]) of drug and/or alcohol abuse that may prevent trial compliance based on investigator judgment.
- Taken any medication within 14 days before the first dose of IP, or hormonal drug products and traditional Chinese medicines within 30 days before the first dose of IP, with the exception of allowed medications listed in the study protocol.
- Participation in any other clinical investigation using an experimental drug requiring repeated blood or plasma drawn 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 Visit 1 (Screening).
- Have any clinical condition that might affect the absorption, distribution, biotransformation, or excretion of Aclidinium Bromide/Formoterol Fumarate.
- Have consumed caffeine or any grapefruit-containing products within 48 hours or alcohol within 72 hours before Day -1 at Visit 2.
- Inability to be venipunctured or tolerate venous access as determined by the investigator or designee.
- Inability to use a multidose DPI.
- Subjects unable to give their consent, or subjects of consenting age but under guardianship, or vulnerable subjects.
- In the opinion of the PI, subjects who are unlikely to comply with the protocol requirements, instructions, and trial-related restrictions.
- Previously taken Aclidinium or previously participated in an investigational study of Aclidinium within 6 months of Day 1
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa, Open-Label, Repeat-Dose Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide/Formoterol Fumarate Fixed Dose Combination Administered Twice-Daily by Inhalation in Chinese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
A Phase IIa, open-label, repeat-dose trial to investigate the pharmacokinetics (PK), safety and tolerability of single and multiple twice daily doses of inhaled Aclidinium Bromide/Formoterol Fumarate 400/12 μg in 20 Chinese male and female patients with stable moderate to severe COPD.
Read the detailed description
Screening will be performed within 21 days of dosing on Day 1 at visit 2. Eligible participants will be admitted to the trial center the day preceding the first dosing (day -1).
Participants will receive Aclidinium Bromide/Formoterol Fumarate 400/12 μg twice-daily (morning and evening) on Days 1 to 4. On Day 5 patients will receive the morning dose only. PK and safety assessments will be conducted at specific timepoints on Day 1 to Day 7.
Participants will be discharged 48 h after the last administration of investigational product and completion of the 48-h PK sample collection and safety assessments on Day 7.
A follow-up visit will be performed within 5 days of the last PK sample collection on Day 7.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Aclidinium Bromide/Formoterol Fumarate 400/12μg BID
- Keywords
- COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aclidinium Bromide/Formoterol Fumarate 400/12μg BIDDrug
Aclidinium bromide/formoterol fumarate 400/12μg administered by inhalation via the Genuair® multidose dry powder inhaler, twice daily (morning and evening) for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Aclidinium Bromide/Formoterol Fumarate 400/12μg BID | Experimental | Aclidinium bromide/Formoterol Fumarate 400/12μg inhalation powder twice-daily. Oral inhalation via Genuair® dry powder inhaler (DPI). Receives: Drug: Aclidinium Bromide/Formoterol Fumarate 400/12μg BID |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Observed maximum concentration, taken directly from the individual concentration-time curve (first dose).
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Tmax of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Time to maximum concentration (h), taken directly from the individual concentration-time curve (first dose).
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Cmin of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Minimum plasma drug concentration at the end of the dosing interval (first dose), where possible.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
AUC(Last) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
AUC(Tau) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Area under the plasma concentration curve during the first dosing interval, tau (first dose).
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Css,Max of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Observed maximum concentration, taken directly from the individual concentration-time curve at steady state.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Css,Min of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Observed minimum concentration, taken directly from the individual concentration-time curve within a dosing interval on Day 5.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Tss,Max of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time to maximum concentration (h), taken directly from the individual concentration-time curve at steady state.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
λz of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Terminal rate constant, estimated by log-linear least square regression of the terminal part of the concentration-time curve.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
t½λz of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Terminal half-life (h), estimated as (ln2)/λz.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
AUC(ss,Tau) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Area under the plasma concentration curve during the dosing interval, tau at steady state.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
CL/F of Aclidinium Bromide and Formoterol Fumarate (Multiple Doses).
Apparent plasma clearance for parent drug estimated as dose divided by AUCss
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Vz/F of Aclidinium Bromide and Formoterol Fumarate (Multiple Doses).
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Cav of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Average plasma concentration during a dosing interval, estimated as AUC(ss,tau)/12
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
%Fluctuation of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Fluctuation index during a dosing interval estimated as 100*(Cmax-Cmin)/Cav (%).
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Rac(Cmax) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Accumulation ratio for Cmax estimated as Css,max on Day 5/Cmax on Day 1
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Rac[AUC(Tau)] of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Accumulation ratio for AUC(tau) estimated as AUC(ss,tau) on Day 5/AUC(tau) on Day 1
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Rac(Cmin) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Accumulation ratio for Cmin estimated as Css,min on Day 5/Cmin on Day 1.
Additional parameters may be determined where appropriate.
Measured: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Secondary outcomes (6)
Adverse Events (AEs)/Serious AEs (SAEs)
Assessment of the safety in terms of the incidences of AEs/SAEs after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days.
Measured: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Blood Pressure
Assessment of the safety in terms of notable changes from baseline in blood pressure after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days.
Measured: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Clinical Laboratory Parameters (Haematology)
Assessment of the safety in terms of haematology parameters after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days.
Measured: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Clinical Laboratory Parameters (Urinalysis)
Assessment of the safety in terms of urinalysis parameters after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days.
Measured: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Clinical Laboratory Parameters (Serum Biochemistry)
Assessment of the safety in terms of serum biochemistry parameters (Alanine aminotransferase [ALT], Aspartate aminotransferase [AST], alkaline phosphatase [ALP], Gamma-glutamyl transferase [GGT], bilirubin, creatine kinase, lactate dehydrogenase, urea nitrogen, creatinine, urate, cholesterol, glucose, sodium, potassium, calcium, chloride, phosphate, protein, and albumin) after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days.
Measured: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to 12-lead ECG Parameters
Assessment of the safety in terms of the 12-lead ECG parameters after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days.
Measured: Screening (Day -21) to Follow-up visit (Days 8-12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start23 Nov 2017
- Primary completion12 Jun 2018
- Study completion12 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zhenxiang Yu, Principal investigator, Pneumology Department, The First Hospital of Jilin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276078
- Sponsor's protocol ID
- D6572C00001
- Other IDs
- M-AS464-01
- Status last verified
- May 2019
- First submitted
- 7 Sep 2017
- Last updated
- 22 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang H, Daoud SZ, Gillen MS, Calderon N, Heijer M, Molins E, Garcia-Gil E, Chen H, Li Q, Liu C, Ding Y. An Evaluation of the Pharmacokinetics, Safety, and Tolerability of Aclidinium/Formoterol Fixed-Dose Combination Administered in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease. Drugs R D. 2022 Mar;22(1):35-42. doi: 10.1007/s40268-021-00374-z. Epub 2022 Feb 8.
PubMed 35133636
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Open-Label, Repeat-Dose Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide/Formoterol Fumarate Fixed Dose Combination Administered Twice-Daily by Inhalation in Chinese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT03276078
- Acronym / sponsor ID
- D6572C00001
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- COPD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 23 Nov 2017 (actual)
- Primary completion
- 12 Jun 2018 (actual)
- Study completion
- 12 Jun 2018 (actual)
- First posted
- 8 Sep 2017 (actual)
- Results
- Posted 22 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase IIa, open-label, repeat-dose trial to investigate the pharmacokinetics (PK), safety and tolerability of single and multiple twice daily doses of inhaled Aclidinium Bromide/Formoterol Fumarate 400/12 μg in 20 Chinese male and female patients with stable moderate to severe COPD.
Detailed description
Screening will be performed within 21 days of dosing on Day 1 at visit 2. Eligible participants will be admitted to the trial center the day preceding the first dosing (day -1).
Participants will receive Aclidinium Bromide/Formoterol Fumarate 400/12 μg twice-daily (morning and evening) on Days 1 to 4. On Day 5 patients will receive the morning dose only. PK and safety assessments will be conducted at specific timepoints on Day 1 to Day 7.
Participants will be discharged 48 h after the last administration of investigational product and completion of the 48-h PK sample collection and safety assessments on Day 7.
A follow-up visit will be performed within 5 days of the last PK sample collection on Day 7.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aclidinium Bromide/Formoterol Fumarate 400/12μg BID | Experimental | Drug: Aclidinium Bromide/Formoterol Fumarate 400/12μg BIDAclidinium bromide/Formoterol Fumarate 400/12μg inhalation powder twice-daily. Oral inhalation via Genuair® dry powder inhaler (DPI). |
Who may qualify
- Ages
- 40 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 procedures and restrictions.
- Chinese men or non-pregnant, non-lactating women, aged ≥40 years old at Visit 1 (Screening).
- Patients with a diagnosis of COPD (GOLD guidelines) for a period of at least 6 months prior to Visit 1 (screening).
- Current or former smokers with a smoking history of ≥10 pack-years.
- Patients with moderate to severe stable COPD (Stage II or Stage III, according to GOLD Guidelines) at Visit 1: post-bronchodilator FEV1 ≥30% and <80% and post-bronchodilator FEV1/FVC <70%.
Key exclusion criteria (29 listed)
- Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff) or patients employed by or relatives of the employees of the site or sponsor.
- Previous enrolment or randomisation in the present study.
- History or current diagnosis of asthma.
- Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation (including the mild COPD exacerbation) within 6 weeks prior to screening or during the run-in period.
- Patients hospitalized for COPD exacerbation (an emergency room visit for longer than 24 hours will be considered a hospitalization) within 3 months prior to screening and during the run-in period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aclidinium Bromide/Formoterol Fumarate 400/12μg BIDAclidinium bromide/formoterol fumarate 400/12μg administered by inhalation via the Genuair® multidose dry powder inhaler, twice daily (morning and evening) for 5 days | Drug | Aclidinium Bromide/Formoterol Fumarate 400/12μg BID |
Primary outcome
Cmax of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Observed maximum concentration, taken directly from the individual concentration-time curve (first dose).
Tmax of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Time to maximum concentration (h), taken directly from the individual concentration-time curve (first dose).
Cmin of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Minimum plasma drug concentration at the end of the dosing interval (first dose), where possible.
AUC(Last) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration.
AUC(Tau) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
Area under the plasma concentration curve during the first dosing interval, tau (first dose).
Css,Max of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Observed maximum concentration, taken directly from the individual concentration-time curve at steady state.
Css,Min of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Observed minimum concentration, taken directly from the individual concentration-time curve within a dosing interval on Day 5.
Tss,Max of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Time to maximum concentration (h), taken directly from the individual concentration-time curve at steady state.
λz of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Terminal rate constant, estimated by log-linear least square regression of the terminal part of the concentration-time curve.
t½λz of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Terminal half-life (h), estimated as (ln2)/λz.
AUC(ss,Tau) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Area under the plasma concentration curve during the dosing interval, tau at steady state.
CL/F of Aclidinium Bromide and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Apparent plasma clearance for parent drug estimated as dose divided by AUCss
Vz/F of Aclidinium Bromide and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz.
Cav of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Average plasma concentration during a dosing interval, estimated as AUC(ss,tau)/12
%Fluctuation of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Fluctuation index during a dosing interval estimated as 100*(Cmax-Cmin)/Cav (%).
Rac(Cmax) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Accumulation ratio for Cmax estimated as Css,max on Day 5/Cmax on Day 1
Rac[AUC(Tau)] of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Accumulation ratio for AUC(tau) estimated as AUC(ss,tau) on Day 5/AUC(tau) on Day 1
Rac(Cmin) of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Multiple Doses).
Time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
Accumulation ratio for Cmin estimated as Css,min on Day 5/Cmin on Day 1. Additional parameters may be determined where appropriate.
6 secondary outcomes
Adverse Events (AEs)/Serious AEs (SAEs)
Time frame: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Blood Pressure
Time frame: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Clinical Laboratory Parameters (Haematology)
Time frame: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Clinical Laboratory Parameters (Urinalysis)
Time frame: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to Clinical Laboratory Parameters (Serum Biochemistry)
Time frame: Screening (Day -21) to Follow-up visit (Days 8-12)
Treatment-emergent AEs Related to 12-lead ECG Parameters
Time frame: Screening (Day -21) to Follow-up visit (Days 8-12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35133636Zhang H, Daoud SZ, Gillen MS, Calderon N, Heijer M, Molins E, Garcia-Gil E, Chen H, Li Q, Liu C, Ding Y. An Evaluation of the Pharmacokinetics, Safety, and Tolerability of Aclidinium/Formoterol Fixed-Dose Combination Administered in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease. Drugs R D. 2022 Mar;22(1):35-42. doi: 10.1007/s40268-021-00374-z. Epub 2022 Feb 8.
- Statistical Analysis Plan (SAP)Link provided by the sponsor.
- ProtocolLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhenxiang Yu principal investigator
Pneumology Department, The First Hospital of Jilin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aclidinium Bromide/Formoterol Fumarate 400/12μg BID in people with Pulmonary Disease, Chronic Obstructive, run by AstraZeneca at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax of Aclidinium Bromide, Its Metabolites and Formoterol Fumarate (Single Dose). (time frame: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03276078, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019.