Effect of Age-gender on the Pharmacokinetic and Pharmacodynamic Profiles of BIA 5 1058
- Registration Number
- NCT04991194
- Lead Sponsor
- Bial - Portela C S.A.
- Brief 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
- Detailed 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 & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 61
All subjects (young and elderly):
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A signed and dated informed consent form before any study-specific screening procedure was performed;
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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);
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Non-smoker or ex-smokers for at least 3 months at screening;
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BMI between 18 and 30 kg/m2, inclusive;
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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;
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Clinical laboratory test results clinically acceptable at screening and admission to the study;
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Negative screen for alcohol and drugs of abuse at screening and admission to the study;
If male:
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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;
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Refraining from donating sperm throughout the study.
Young subjects only:
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Males and females aged between 18 and 40 years, inclusive.
If female:
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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;
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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;
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If of childbearing potential, negative serum pregnancy test at screening and negative urine pregnancy test on admission to the study.
Elderly subjects only:
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Males and females older than 65 years, inclusive.
All subjects (young and elderly):
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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;
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Clinically relevant surgical history;
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History of relevant atopy or drug hypersensitivity;
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History of alcoholism or drug abuse;
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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];
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Significant infection or known inflammatory process at screening or admission to study;
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Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the study;
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Previous use of BIA 5-1058;
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Use of any investigational drug or participation in any clinical trial within 90 days prior to screening;
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Participation in more than 2 clinical trials within the 12 months prior to screening;
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Donation or reception of any blood or blood products within the 3 months prior to screening;
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Vegetarians, vegans or other medical dietary restrictions;
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Not able to communicate reliably with the Investigator;
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Unlikely to co-operate with the requirements of the study.
If male:
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Not using an accepted effective method of contraception;
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Refusing to refrain from donating sperm throughout the study.
Young subjects only:
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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:
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Pregnant or breastfeeding;
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Not using an accepted effective contraceptive method or using oral contraceptives.
Elderly subjects only:
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIA 5-1058 1200 mg (Part I) BIA 5-1058 Subjects received 1200 mg of BIA 5-1058 once a day (od), in fasting conditions, for 10 days BIA 5-1058 400 mg (Part II) BIA 5-1058 Subjects received 400 mg of BIA 5-1058 od, in fasting conditions, for 10 days.
- Primary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) Up to 4 weeks 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).Time of occurrence of Cmax (tmax) Up to 4 weeks 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).Area under the plasma concentration-time curve from time zero to 24 hours after last dosing (AUC0-24) Up to 4 weeks 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).Apparent total body clearance (CL/F) Up to 4 weeks 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).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) Up to 4 weeks 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).Apparent terminal half-life (t½) Up to 4 weeks 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).
- Secondary Outcome Measures
Name Time Method