Pulmonary Arterial Hypertension
Conditions
Brief summary
The purpose of this study is to assess the effect of BIA 5-1058 200 mg on the pharmacokinetic (PK) of treprostinil
Detailed description
This study was an open-label, three period, fixed sequence study in healthy male and female subjects performed at a single study center. The study comprised: * Screening during Days -28 to -2 (both inclusive). * Three treatment periods separated by a washout period of at least 10 days.
Interventions
DRUGBIA 5-1058
200 mg (2 x 100 mg tablets), oral route
DRUGtreprostinil
1 mg (1 extended-release tablet), oral route
Sponsors
Bial - Portela C S.A.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provided a signed and dated informed consent before any study specific procedures were conducted. 2. Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit. 3. Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error. 4. Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit. 5. Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period. 6. Negative test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBc), immunoglobulin M (IgM) anti-HBc, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus (HIV) (Types 1 and 2) antibodies at the Screening Visit. 7. Negative screen for alcohol and drugs of abuse at the Screening Visit and on admission to each treatment period. 8. Subject had to be willing and able to be confined to the clinical unit and had to adhere to the study and lifestyle restrictions. 9. Contraception requirements: Male subjects had to use together with his female partner/spouse a highly effective contraception form of birth control in combination with a barrier method throughout the clinical study period and agreed not to father a child or to donate sperm starting at the Screening Visit and throughout the clinical study. Female subjects had to either be of non childbearing potential or had to use highly effective methods of contraception from at least 3 months before the Screening Visit and throughout the clinical study in combination with a barrier method.
Exclusion criteria
Inclusion Criteria: Subjects who met the following criteria were considered eligible to participate/continue in the study: 1. Provided a signed and dated informed consent before any study specific procedures were conducted. 2. Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit. 3. Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error. 4. Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit. 5. Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period. 6. Negative test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBc), immunoglobulin M (IgM) anti-HBc, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus (HIV) (Types 1 and 2) antibodies at the Screening Visit. 7. Negative screen for alcohol and drugs of abuse at the Screening Visit and on admission to each treatment period. 8. Subject had to be willing and able to be confined to the clinical unit and had to adhere to the study and lifestyle restrictions. 9. Contraception requirements: Male subjects had to use together with his female partner/spouse a highly effective contraception form of birth control in combination with a barrier method throughout the clinical study period and agreed not to father a child or to donate sperm starting at the Screening Visit and throughout the clinical study. Female subjects had to either be of non childbearing potential or had to use highly effective methods of contraception from at least 3 months before the Screening Visit and throughout the clinical study in combination with a barrier method.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration - Cmax | Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours | Primary Pharmacokinetic Parameters - BIA 5 1058 |
| Area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration - AUC0-t | Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours | Primary Pharmacokinetic Parameters - BIA 5 1058 |
| AUC from time zero extrapolated to infinity - AUC0-inf | Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours | Primary Pharmacokinetic Parameters - BIA 5 1058 |
| Maximum observed plasma concentration at steady state - Cmax,ss | Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours. | Primary Pharmacokinetic Parameters - Treprostinil |
| AUC over the dosing interval at steady state - AUC0-τ,ss | Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours. | Primary Pharmacokinetic Parameters - Treprostinil |
Countries
Germany
Outcome results
None listed