Pharmacokinetics, Safety and Tolerability of Concurrent Doses of BIA 5-1058 and Furosemide

NCT07173738 | Completed Phase 1

• 2 other identifiers: BIA-51058-1112017-002807-93
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is:

• To assess the effect of BIA 5 1058 400 mg on furosemide pharmacokinetics (PK).
• To assess the effect of furosemide 40 mg on the PK of BIA 5 1058.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension (PAH); BIA 5-1058; Zamicastat; Furosemide; Dopamine ß-hydroxylase (DßH) inhibitor; BIAL

Outcome Measures

Primary Outcomes (9)

• Maximum observed concentration (Cmax)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• Time to Cmax (Tmax)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• Elimination rate constant (kel)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• Terminal elimination half-life (t1/2)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• Area under the concentration-time curve (AUC) from time of dosing to last measurable concentration (AUC0-t)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• AUC extrapolated to infinity (AUC0-inf)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• Clearance (CL/F)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• Volume of distribution (Vz/F)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

• AUC% extrapolated (residual area)

  Will be calculated from the treatment periods 1, 2 and 3, days 1 to 4, BIA 5-1058 and furosemide concentration-time data

  Up to 3 months

Study Arms (3)

BIA 5-1058

EXPERIMENTAL

Period 1: Single oral dose of BIA 5-1058 400 mg

Drug: BIA 5-1058

Furosemide

EXPERIMENTAL

Period 2: 40 mg furosemide (single oral dose)

Drug: Furosemide

BIA 5-1058 and Furosemide

EXPERIMENTAL

Period 3: 40 mg furosemide (single oral dose) concomitant with a single oral dose of BIA 5-1058 400 mg

Drug: BIA 5-1058 and Furosemide

Interventions

BIA 5-1058 DRUG

During treatment period 1, a single oral dose of BIA 5-1058 (400 mg) will be administered on the morning of day 1, following an overnight fast of at least 10 h.

Also known as: Period 1

BIA 5-1058

Furosemide DRUG

During treatment period 2, a single oral dose of furosemide (40 mg) will be administered on the morning of day 1, following an overnight fast of at least 10 h.

Also known as: Period 2

Furosemide

BIA 5-1058 and Furosemide DRUG

During treatment period 3, a single oral dose of both investigational medicinal product (IMPs) BIA 5-1058 (400 mg) concomitantly with furosemide (40 mg) will be administered on the morning of day 1, following an overnight fast of at least 10 h.

Also known as: Period 3

BIA 5-1058 and Furosemide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A signed and dated informed consent form before any study-specific screening procedure is performed;
• Males and Females subjects aged 18 to 55 years, inclusive;
• Non-smoker or ex-smokers for at least 3 months prior to screening;
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive;
• Subject with no clinically significant history of previous allergy / sensitivity to BIA 5-1058/furosemide or any of the excipients contained within the IMP(s);
• 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;
• Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period;
• Healthy as determined by the Investigator based on medical history, physical examination, , vital signs (systolic blood pressure (SBP) ≥ 90 mmHg and ≤ 140 mmHg, diastolic blood pressure (DBP) ≥ 50 mmHg and ≤ 90 mmHg) and digital 12-lead electrocardiogram (ECG));
• Clinical laboratory test results clinically acceptable at screening and admission to each treatment period;
• If male:
• Male subjects and female partner willing to use 2 effective methods of contraception, i.e., established method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of IMP.
• Refraining from donating sperm throughout the study and for 3 months after the last dose of IMP;
• 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;
• If of childbearing potential, using an effective non-hormonal method of contraception \[intrauterine device; condom or occlusive cap (diaphragm or cervical or vault caps) with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he is the sole partner of that subject\] for all the duration of the study and for 3 months after the last dose of IMP;

You may not qualify if:

• Any personal or family history of haemostatic disorder;
• Consumption of more than 21 units (14 units for female subjects) of alcohol a week \[1 unit corresponds to 1 glass of 12% wine (10 cl), 1 glass of 45% pastis (2.5 cl), 1 glass of 40% whisky (2.5 cl), 1 glass of 12% champagne (10 cl), 1 glass of 18% aperitif drink (7 cl) or one 25-cl glass of 5% beer\];
• Use of nicotine replacement products such as patches, gum and/or electronic cigarettes within 3 months prior to the screening visit;
• Significant infection or known inflammatory process at screening or admission to each treatment period;
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period;
• Symptomatic orthostatic hypotension \[drop of \> 20 mmHg in SBP and/or \> 10 mmHg\] in DBP when moving from supine to standing position, together with other symptoms, e.g. dizziness
• Previous use of BIA 5-1058;
• Use of any investigational drug or participation in any clinical trial within 90 days or 5 half-life times, whichever is longer,
• Participation in more than 4 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;
• Use of medicines within 28 days of initiation of treatment that may affect the safety or other study assessments, in the Investigator's opinion or intake of any of the prohibited medications.
• Clinically relevant history or presence of respiratory, gastrointestinal, hepatic, renal, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders;

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Simbec Research Ltd (Simbec)

Merthyr Tydfil, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Officials

• Annelize Koch, Dr

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 15, 2025
• Study Start: June 11, 2018
• Primary Completion: September 7, 2018
• Study Completion: September 7, 2018
• Last Updated: September 15, 2025

Record last verified: 2025-09

Locations

GB (1)