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.

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