A Drug Utilisation Post-authorisation Study of New Users of Aclidinium Bromide (Monotherapy or in Combination) (DUS1/DUS2)

Aclidinium Bromide Drug Utilisation Post-Authorisation Safety Studies (DUS): Common Protocol for Aclidinium (DUS1) and Aclidinium/Formoterol Fixed-Dose Combination (DUS2)

DUS1 and DUS2 are descriptive drug utilisation studies in new users of aclidinium bromide in Europe.

The objectives of DUS1 and DUS2 are to describe the characteristics and patterns of use of new users of aclidinium bromide (monotherapy or in combination) and new users of other medications for chronic obstructive pulmonary disease (COPD); to evaluate the potential off-label use of aclidinium bromide; to describe users of aclidinium bromide in subgroups of patients for whom there is missing information in the risk management plan (RMP); and to establish a core cohort of new users of aclidinium bromide for the future evaluation of safety concerns described in the RMP.

The data source for these studies will be the CRPD in the UK, the GePaRD in Germany, and national health databases in Denmark.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Aclidinium bromide; Drug: Aclidinium bromide/formoterol; Drug: Other COPD medication

Detailed Description

DUS1 will be conducted when the target number of new users of aclidinium monotherapy is reached, and DUS2 when the target number of new users of aclidinium fixed-dose combination with formoterol is reached.

As this was a descriptive study no primary or secondary endpoints were specified.

• Study Type: Observational
• Enrollment (Actual): 22155

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark
    • National Health Database Denmark, Southern Denmark University
• Germany
  • Bremen, Germany
    • German Pharmacoepidemiological Research Database
• United Kingdom
  • London, United Kingdom
    • Clinical Practice Research Datalink

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

New users of aclidinium bromide (on monotherapy or with concomitant use of formoterol) and new users of other COPD medications will be identified and included in the specific exposure cohort of interest.

Description

Inclusion Criteria:

• Patients in the study will be required to meet the following criteria, as ascertained from each of the automated databases:
• To have at least 1 year of enrolment in the database (DUS1 and DUS2).
• To have not been prescribed aclidinium bromide as monotherapy or with concomitant use of formoterol during the 6 months before the date of first prescription of aclidinium bromide (index date) in DUS1
• To have not been prescribed aclidinium bromide as monotherapy, with concomitant use of formoterol, or as aclidinium/formoterol during the 6 months before the date of first prescription of aclidinium bromide (index date) in DUS2

The same inclusion criteria will be applied for each of the comparator drugs.

Exclusion Criteria:

• No age restrictions or exclusion criteria will be applied. This will allow for the characterisation of all users of aclidinium bromide and comparator drugs irrespective of the indication for which these medications are used. Identification of potential off-label use of aclidinium bromide in the paediatric and adult populations is one of the specific objectives of this DUS.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aclidinium bromide monotherapy; In DUS1, all new users of aclidinium either on monotherapy or with concomitant formoterol will be included. In addition, in DUS2, all new users of the fixed-dose combination of aclidinium/formoterol and any other new fixed-dose combinations of LAMAs and LABAs that become available during the study and that are captured in each database will be included.	Drug: Aclidinium bromide; Administered as monotherapy, prescribed as recorded in the database.
Aclidinium bromide and formoterol; In DUS1, all new users of aclidinium either on monotherapy or with concomitant formoterol will be included. In addition, in DUS2, all new users of the fixed-dose combination of aclidinium/formoterol and any other new fixed-dose combinations of LAMAs and LABAs that become available during the study and that are captured in each database will be included.	Drug: Aclidinium bromide/formoterol; Administered in combination with formoterol fumarate (concomitant or as a fixed-dose combination), prescribed as recorded in the database.
New users of other COPD medication; New users of other COPD medications (tiotropium, other LAMAs, LABA, LABA/ICS, LAMA/LABA), prescribed as recorded in the database.	Drug: Other COPD medication; Other COPD medication including: tiotropium; other long-acting anticholinergic (LAMAs; lycopyrronium bromide, umeclidinium); LABA (formoterol, salmeterol, indacaterol); LABA/ICS (formoterol/budesonide, formoterol/beclometasone, formoterol/mometasone, formoterol/fluticasone, salmeterol/fluticasone propionate, and vilanterol/fluticasone); LAMA/LABA (approved or under regulatory review or in development; glycopyrrolate/formoterol, glycopyrronium/indacaterol, tiotropium/olodaterol, umeclidinium/vilanterol), prescribed as recorded in the database.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline age of new users		Baseline (date of first prescription)
Baseline frequency of new users with a diagnosis of COPD including emphysema or chronic bronchitis		Baseline (date of first prescription)
Baseline frequency of new users with severe COPD	COPD severity including recent exacerbations	Baseline (date of first prescription)
Baseline frequency of new users with a history of cardiovascular disease	Baseline history of cardiovascular diseases and baseline cardiovascular risk profile, including diabetes, recent acute myocardial infarction (AMI), unstable angina, arrhythmias, or heart failure	Baseline (date of first prescription)
Overall comorbidity index of new users		From date of first prescription up to 1 year of follow-up
Frequency of respiratory medication use by new users		From date of first prescription to 1 year of follow-up
Baseline gender of new users		Baseline (date of first prescription)
Frequency of users of aclidinium bromide with comorbid asthma diagnoses or in the absence of other drugs or diagnoses suggestive of COPD		From date of first prescription up to 1 year of follow-up
Frequency of pregnancies during use of COPD medication		From date of first prescription up to 1 year of follow-up
Frequency of use of aclidinium bromide in the pediatric population		From date of first prescription up to 1 year of follow-up
Frequency of comorbid conditions in the paediatric population		From date of first prescription up to 1 year of follow-up
Baseline frequency of patients with renal or hepatic impairment		Baseline (date of first prescription)
Baseline frequency of patients who have experienced a recent exacerbation		Baseline (date of first prescription
Baseline frequency of patients with thyrotoxicosis or pheochromocytoma		Baseline (date of first prescription)
Frequency of previous smoking in new users		From date of first prescription to 1 year of follow-up
Frequency of current smokers in new users		From date of first prescription to 1 year of follow-up
Frequency of new users with BMI <18.50 kg/m2 (underweight)		From date of first prescription to 1 year of follow-up
Frequency of new users with BMI ranging from 18.50 to 24.99 kg/m2 (normal weight)		From date of first prescription to 1 year of follow-up
Frequency of new users with BMI >25.0 kg/m2 (overweight)		From date of first prescription to 1 year of follow-up
Frequency of new users with BMI ranging between 25.0 and 29.99 kg/m2 (pre-obese)		From date of first prescription to 1 year of follow-up
Frequency of new users with BMI >30 kg/m2 (obese)		From date of first prescription to 1 year of follow-up
Frequency of new users with low socioeconomic status (Townsend multiple deprivation index)		From date of first prescription to 1 year of follow-up
Baseline frequency of patients with benign prostatic hyperplasia		Baseline (date of first prescription)
Baseline frequency of patients with bladder neck obstruction		Baseline (date of first prescription)
Baseline frequency of patients with urinary retention		Baseline (date of first prescription)
Baseline frequency of patients with narrow-angle glaucoma		Baseline (date of first prescription)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of COPD medication use	Duration of use will be estimated through the number of consecutive prescriptions, with a maximum interval of 60 days between them, or the days of supply of each prescription, as available in each database.	From date of first prescription up to 1 year of follow-up
Average daily dose of COPD medication	The daily dose for each treatment will be derived from the recorded dose or from the time between consecutive prescriptions and prescribing information (strength, number of units, and number of boxes) according to the available information in each database.	From date of first prescription up to 1 year of follow-up
Adherence to COPD medication within 1 year	Consecutive prescriptions are defined as those with a maximum gap of 60 days between the date of prescriptions. Proportion of patients refilling prescriptions within 60 days from the end of the previous prescription.	From date of first prescription up to 1 year of follow-up
Frequency of use of concomitant medications		From date of first prescription up to 1 year of follow-up
Frequency of switching between COPD medications		From date of first prescription up to 1 year of follow-up
Total number of prescriptions		From date of first prescription up to 1 year of follow-up

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: RTI Health Solutions
• Investigators: Study Director: Jordi Castellsague, MD, MPH, RTI Health Solutions; Study Director: Susana Perez-Gutthann, MD, PhD, RTI Health Solutions

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2015
• Primary Completion (Actual): February 28, 2017
• Study Completion (Actual): February 28, 2017

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: February 20, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Bromides; Formoterol Fumarate
• Other Study ID Numbers: D6560R00005; EUPAS6559 (Registry Identifier: ENCePP)