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

NCT04991194 | Terminated Phase 1

• 2 other identifiers: BIA-51058-1052015-003682-28
• Study Type: interventional
• Target: 61
• Locations: 0 countries
• Sites: N/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

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

BIA 5-1058 1200 mg (Part I)

EXPERIMENTAL

Subjects received 1200 mg of BIA 5-1058 once a day (od), in fasting conditions, for 10 days

Drug: BIA 5-1058

BIA 5-1058 400 mg (Part II)

EXPERIMENTAL

Subjects received 400 mg of BIA 5-1058 od, in fasting conditions, for 10 days.

Drug: BIA 5-1058

Interventions

BIA 5-1058 DRUG

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.

Also known as: Zamicastat

BIA 5-1058 1200 mg (Part I); BIA 5-1058 400 mg (Part II)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects (young and elderly):
• A signed and dated informed consent form before any study-specific screening procedure was performed;
• 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);
• Non-smoker or ex-smokers for at least 3 months at screening;
• BMI between 18 and 30 kg/m2, inclusive;
• 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;
• Clinical laboratory test results clinically acceptable at screening and admission to the study;
• Negative screen for alcohol and drugs of abuse at screening and admission to the study;
• If male:
• 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;
• Refraining from donating sperm throughout the study.
• Young subjects only:
• Males and females aged between 18 and 40 years, inclusive.
• If female:
• 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;

You may not qualify if:

• All subjects (young and elderly):
• 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;
• Clinically relevant surgical history;
• History of relevant atopy or drug hypersensitivity;
• History of alcoholism or drug abuse;
• Consumption of more than 14 units of alcohol a week \[1 unit corresponds to 1 glass of 12° wine (10 cL), 1 glass of 45° pastis (2.5 cL), 1 glass of 40° whisky (2.5 cL), 1 glass of 12° champagne (10 cL), 1 glass of 18°aperitif drink (7 cL) or one 25-cL glass of 5°beer\];
• Significant infection or known inflammatory process at screening or admission to study;
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the study;
• Previous use of BIA 5-1058;
• Use of any investigational drug or participation in any clinical trial within 90 days prior to screening;
• Participation in more than 2 clinical trials within the 12 months prior to screening;
• Donation or reception of any blood or blood products within the 3 months prior to screening;
• Vegetarians, vegans or other medical dietary restrictions;
• Not able to communicate reliably with the Investigator;
• Unlikely to co-operate with the requirements of the study.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

zamicastat

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 5, 2021
• Study Start: October 12, 2015
• Primary Completion: December 30, 2016
• Study Completion: December 30, 2016
• Last Updated: August 5, 2021

Record last verified: 2021-07