Effect of Food on BIA 5-1058

Phase 1

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: BIA 5-1058

• Registration Number: NCT04991155
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

The aim of this study is to investigate the effect of food on the pharmacokinetic (PK) profile of BIA 5-1058 after a single dose in healthy subjects.

Detailed Description

Single-centre, open-label, randomised, single-dose, three-way crossover, three-part study in 54 healthy subjects.

Duration of treatment:

The study comprised a screening evaluation between 2 and 28 days before the first IMP (Investigational Medicinal Product) administration and 3 treatment periods of approximately 4 days, separated by wash-out periods of at least 7 days. A follow-up visit was performed approximately 7 days after discharge from the last period or early discontinuation. For each subject, the full duration of the participation in the study was approximately 9 weeks.

Study Timeline

• Study Start: 2015-07-20
• Primary Completion: 2015-09-22
• Study Completion: 2015-09-22
• Status Verified: 2021-07
• Study First Submitted: 2021-07-28
• Study First Submitted QC: 2021-07-28
• Last Update Submitted: 2021-07-28
• Study First Posted: 2021-08-05
• Last Update Posted: 2021-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

1. Able and willing to give written informed consent and to comply with the study restrictions;

2. Male or female subjects aged 18 to 45 years, inclusive;

3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive;

4. Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead electrocardiogram (ECG);

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 each treatment period;

7. Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period;

8. Non-smokers or ex-smokers for at least 3 months.

   If female:

9. 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;

10. If of childbearing potential, she was 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;

11. Negative serum pregnancy test at screening and negative urine pregnancy test on admission of each treatment period (women of childbearing potential only).

    If male:

12. 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;

13. Refraining from donating sperm throughout the study.

Exclusion Criteria

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 glass (25 cL) of beer with 3° of alcohol = 7.5 g, or 1 glass (25 cL) of beer with 6° of alcohol = 15 g, or 1 glass (12.5 cL) of wine with 10° of alcohol = 12 g, or 1 glass (4cL) of aperitif with 42° of alcohol = 17 g];

6. Significant infection or known inflammatory process at screening or admission to each treatment period;

7. Display of acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period;

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

9. Previous administration of BIA 5-1058;

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

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

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

13. Vegetarians, vegans or had any other medical dietary restrictions;

14. Not able to communicate reliably with the Investigator;

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

    If female:

16. Pregnant or breastfeeding;

17. Not using an accepted effective contraceptive method or was using oral contraceptives.

    If male:

18. Not using an accepted effective method of contraception;

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
PART 1 (400 mg BIA 5-1058)	BIA 5-1058	Each subject was orally administered a single oral dose of BIA 5-1058 on D1 (dosing day) on three different occasions (Period 1, Period 2 and Period 3): Part 1: 400 mg BIA 5-1058 as four (4) 100 mg tablets in Period 1, 400 mg BIA 5-1058 as four (4) 100 mg tablets in Period 2, and 400 mg BIA 5-1058 as four (4) 100 mg tablets in Period 3.
PART 2 (800 mg BIA 5-1058)	BIA 5-1058	Each subject was orally administered a single oral dose of BIA 5-1058 on D1 (dosing day) on three different occasions (Period 1, Period 2 and Period 3): Part 2: 800 mg BIA 5-1058 as eight (8) 100 mg tablets in Period 1, 800 mg BIA 5-1058 as eight (8) 100 mg tablets in Period 2, and 800 mg BIA 5-1058 as eight (8) 100 mg tablets in Period 3.
PART 3 (1200 mg BIA 5-1058)	BIA 5-1058	Each subject was orally administered a single oral dose of BIA 5-1058 on D1 (dosing day) on three different occasions (Period 1, Period 2 and Period 3): Part 3: 1200 mg BIA 5-1058 as twelve (12) 100 mg tablets in Period 1, 1200 mg BIA 5-1058 as twelve (12) 100 mg tablets in Period 2, and 1200 mg BIA 5-1058 as twelve (12) 100 mg tablets in Period 3.

Primary Outcome Measures

Name	Time	Method
Maximum observed plasma concentration (Cmax)	Up to 9 weeks	In all treatment periods, blood samples were taken at the following times: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose
Area under the plasma concentration-time curve (AUC)	Up to 9 weeks	In all treatment periods, blood samples were taken at the following times: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose
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-last)	Up to 9 weeks	In all treatment periods, blood samples were taken at the following times: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose
Time of occurrence of Cmax (tmax)	Up to 9 weeks	In all treatment periods, blood samples were taken at the following times: before BIA 5-1058 dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose