Effect of Age-gender on the Pharmacokinetic and Pharmacodynamic Profiles of BIA 5 1058

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Effect of Age-gender on the Pharmacokinetic and Pharmacodynamic Profiles of BIA 5 1058. An Open-label, Parallel Group, Multiple Dose 10-day Study.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04991194
• Other study ID #: BIA-51058-105
• Secondary ID: 2015-003682-28
• Status: Terminated
• Phase: Phase 1
• Start date: October 12, 2015
• Est. completion date: December 30, 2016

Study information

• Verified date: July 2021
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

the purpose of this study is to determine the effect of age on the Pharmacokinetics (PK) profile of BIA 5-1058 at steady state after multiple oral doses

Description:

This was a single-centre, open-label, parallel group, non-randomised, two-part multiple dose 10-day study in healthy young and elderly male and female subjects. The study comprised a screening evaluation between 2 and 28 days before the first Investigational Medicinal Product (IMP) administration, a hospitalisation period of 15 days comprising a treatment period of 10 days, and a follow-up visit approximately 7 days after discharge.

Part 1: Subjects received 1200 mg of BIA 5-1058 once a day (od), in fasting conditions, for 10 days Part 2 : Subjects received 400 mg of BIA 5-1058 od, in fasting conditions, for 10 days.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 61
• Est. completion date: December 30, 2016
• Est. primary completion date: December 30, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All subjects (young and elderly):

1. A signed and dated informed consent form before any study-specific screening procedure was performed;

2. Healthy male and female subjects as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs and digital 12-lead electrocardiogram (ECG);

3. Non-smoker or ex-smokers for at least 3 months at screening;

4. BMI between 18 and 30 kg/m2, inclusive;

5. Negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies (HCV Ab) and anti-human immunodeficiency virus antibodies (HIV-1 and HIV-2 Ab) at screening;

6. Clinical laboratory test results clinically acceptable at screening and admission to the study;

7. Negative screen for alcohol and drugs of abuse at screening and admission to the study;

If male:

8. Using an effective method of contraception with a pregnant partner or partner of childbearing potential (condom or occlusive cap [diaphragm or cervical or vault caps] with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomy) throughout the study;

9. Refraining from donating sperm throughout the study.

Young subjects only:

10. Males and females aged between 18 and 40 years, inclusive.

If female:

11. No childbearing potential by reason of surgery or at least 1 year post-menopause (i.e., 12 months post last menstrual period), or menopause confirmed by follicle-stimulating hormone (FSH) testing;

12. If of childbearing potential, using an effective non-hormonal method of contraception [intrauterine device or intrauterine system; condom or occlusive cap (diaphragm or cervical or vault caps) with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he is the sole partner of that subject] for all the duration of the study;

13. If of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test on admission to the study.

Elderly subjects only:

14. Males and females older than 65 years, inclusive.

Exclusion Criteria:

All subjects (young and elderly):

1. Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders;

2. Clinically relevant surgical history;

3. History of relevant atopy or drug hypersensitivity;

4. History of alcoholism or drug abuse;

5. Consumption of more than 14 units of alcohol a week [1 unit corresponds to 1 glass of 12° wine (10 cL), 1 glass of 45° pastis (2.5 cL), 1 glass of 40° whisky (2.5 cL), 1 glass of 12° champagne (10 cL), 1 glass of 18°aperitif drink (7 cL) or one 25-cL glass of 5°beer];

6. Significant infection or known inflammatory process at screening or admission to study;

7. Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the study;

8. Previous use of BIA 5-1058;

9. Use of any investigational drug or participation in any clinical trial within 90 days prior to screening;

10. Participation in more than 2 clinical trials within the 12 months prior to screening;

11. Donation or reception of any blood or blood products within the 3 months prior to screening;

12. Vegetarians, vegans or other medical dietary restrictions;

13. Not able to communicate reliably with the Investigator;

14. Unlikely to co-operate with the requirements of the study.

If male:

15. Not using an accepted effective method of contraception;

16. Refusing to refrain from donating sperm throughout the study.

Young subjects only:

17. Use of medicines within 2 weeks of admission that could affect the safety or other study assessments, in the Investigator's opinion;

If female of childbearing potential:

18. Pregnant or breastfeeding;

19. Not using an accepted effective contraceptive method or using oral contraceptives.

Elderly subjects only:

20. For elderly subjects, previously prescribed medications that interfered with absorption, distribution, metabolism, and excretion or safety/tolerability evaluation of BIA 5-1058 and adrenal or renal function were prohibited; however, previously prescribed medications that did not interfere with absorption, distribution, metabolism, and excretion or safety/tolerability evaluation of BIA 5-1058, adrenal or renal function and which could not interfere with the objectives of the study were allowed if the dose regimen had been stable for at least 4 weeks and was expected to remain stable throughout the study. Such concomitant medications were to be reviewed and mutually agreed upon by the Sponsor and the Investigator.

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• BIA 5-1058
Each subject was administered either 1200 mg (Part 1) or 400 mg (Part 2) BIA 5-1058 od for 10 days, in fasting conditions for 8 hours [Day (D)2 to D9] or 10 hours (D1 and D13), and remained fasted for 2 hours (D2 to D9) or 4 hours (D1 and D13) post-dose. The formulation was tablets 100 mg and the mode of administration was oral.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax)	Pharmacokinetic analysis; Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2).; On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).	Up to 4 weeks
Primary	Time of occurrence of Cmax (tmax)	Pharmacokinetic analysis; Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2).; On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).	Up to 4 weeks
Primary	Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which the drug concentration was at or above the lower limit of quantification (AUC0-t)	Pharmacokinetic analysis; Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2).; On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).	Up to 4 weeks
Primary	Area under the plasma concentration-time curve from time zero to 24 hours after last dosing (AUC0-24)	Pharmacokinetic analysis; Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2).; On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).	Up to 4 weeks
Primary	Apparent terminal half-life (t½)	Pharmacokinetic analysis; Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2).; On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).	Up to 4 weeks
Primary	Apparent total body clearance (CL/F)	Pharmacokinetic analysis; Blood samples for PK analysis were taken at the following times: On D1: before BIA 5-1058 dosing (pre-dose), and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h post-dose (before the second administration on D2).; On D3, D7, D8 and D9: before BIA 5-1058 dosing. From D10 to D13: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 (D11), 36 (D11), 48 (D12), 60 (D12) and 72h post-dose (D13).	Up to 4 weeks