Pharmacokinetic Study of Single and Repeated Dose of Roflumilast 500 µg , in Healthy Chinese Subjects

An Open, Single Centre, Single and Repeated Dose Study to Investigate the Pharmacokinetic Profile of Roflumilast and Roflumilast N-oxide After Administration of 500 μg Dose of Roflumilast in Healthy Chinese Subjects

The primary objective is to assess the pharmacokinetics (PK) of roflumilast and its metabolite roflumilast N-oxide after single and repeated oral administrations of roflumilast 500 μg in healthy Chinese subjects.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Roflumilast

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100032
    • Nycomed Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Healthy male and female (24 male and 8 female) subjects of Chinese ethnic origin, age 40 years and older.
• Assessed as healthy based on a screening examination including medical history, physical examination, blood pressure, pulse rate, ECG assessment, and clinical laboratory results.
• Body weight according to a Body Mass Index (BMI) between 19 and 28 kg/[m²], (both inclusive) and a body weight ≥ 50 kg.
• Females with childbearing potential who are using medically acceptable and reliable method of contraception for the entire study duration, such as tubal ligation, hysterectomy, intrauterine device without hormones or post-menopausal females, the latter is defined as females who have had no menstrual period for at least 2 years.

Main Exclusion Criteria:

• History or current evidence of clinically relevant allergies or idiosyncrasy to drugs or food
• History of allergic reactions to roflumilast or any inactive ingredients of the trial medication
• History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrinological, metabolic, neurological, psychiatric, or other disease (within the last 2 years)
• History of malignancy within the past 5 years
• Electrocardiogram (ECG) abnormalities of clinical relevance (e.g. QTc according to Bazett's formula: QTc > 450 msec (male), QTc > 470 msec (female), PQ ≥ 220 msec)
• Blood pressure ≥ 140 mm HG systolic or ≥ 90 mm HG diastolic
• Elevated transaminases > 2 x upper Limit of normal range and or increased of the total bilirubin > 1.5 upper Limit of normal range
• Clinically relevant abnormalities in clinical chemical, hematological or any other laboratory variables
• Chronic or clinically relevant acute infections
• Proneness to orthostatic dysregulation, faintings, or blackouts
• Positive results in any of the virology tests of acute or chronic infectious HIV and hepatitis A, B, and C virus infections
• Positive drug screen
• Abuse of alcohol or drugs
• Positive β-HCG pregnancy test (female)
• Pregnant or lactating females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roflumilast; (This is a pharmacokinetic study)	Drug: Roflumilast; Period I: single dose of roflumilast 500 μg orally in the morning. Period II: repeated dose of roflumilast 500 μg orally in the morning for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the pharmacokinetic profiles after single and repeated dose of roflumilast 500 µg administered to healthy Chinese subjects.	PK samples at pre-dose, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h and 24h, 36h, 48h, 72h, 96h, 120h, 144h and 168h post dose after single dose and at the time points pre-dose, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 16h and 24h after administration of a repeated dose	Period I: single dose, PK-Investigation over 8 days, Period II: repeated dose for 14 days, PK-Investigation on days 14 and 15

Secondary Outcome Measures

Outcome Measure	Time Frame
The safety and tolerability of single and repeated dose roflumilast 500 µg will be evaluated in terms of adverse event, ECG, blood pressure, pulse rate, and clinical laboratory tests.	During screening, clinical part and final check

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• RO-2455-101-EC-RDS-2012-04-26.pdf

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: May 16, 2011
• First Submitted That Met QC Criteria: May 16, 2011
• First Posted (Estimate): May 17, 2011

Study Record Updates

• Last Update Posted (Estimate): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetic; Roflumilast
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: RO-2455-101-EC