Cardiovascular Disease+Pulmonary DiseasePhase 1NCT03708146
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BIA 5-1058
A Phase 1 study testing BIA 5-1058 in people with Cardiovascular Disease+Pulmonary Disease and Pulmonary Arterial Hypertension, run by Bial - Portela C S.A. at 1 site in United Kingdom.
Trial summary
This is a single centre, double-blind, randomised, placebo-controlled, parallel staggered group study of BIA 5-1058 in 11 different cohorts of 15 healthy subjects. Subjects will be randomly assigned to receive once-daily oral doses of BIA 5-1058 or matching placebo for 10 days. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease+Pulmonary Disease, Pulmonary Arterial Hypertension
- What is being tested?
- BIA 5-1058
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 157 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 May 2018to 18 Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Able and willing to comply with the study restrictions and to give written informed consent before any study procedure; Male or non-pregnant, non-lactating female subjects aged 18 to 55 years, inclusive; Body mass index (BMI) between 18.0 and 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator; Healthy as determined by the investigator based on medical history, physical examination, clinical laboratory test results, vital signs (systolic blood pressure ≥ 90 mmHg and ≤ 150 mmHg, diastolic blood pressure ≥ 50 mmHg and ≤ 90 mmHg) and digital 12-lead ECG); 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 Negative screen for alcohol and drugs of abuse at screening and admission Non-smokers or ex-smokers for at least 3 months;
- Must adhere to the contraception requirements:
- Male subjects and female partner willing to a condom plus an approved method of effective contraception, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from the time of informed consent until 90 days after last dose of IMP. Male subjects must refrain from donating sperm throughout the study and for 90 days after the last dose of IMP; Female subjects of childbearing potential willing to use, with their partner, a condom and an approved method of highly effective contraception from the time of informed consent until 30 days after the last follow-up visit. Hormonal contraceptives are not permitted for female subjects. Female subjects must not donate ova from the time of the first dose until 90 days after the last dose of study drug; If female, nonchildbearing 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 Negative serum pregnancy test at screening and negative urine pregnancy test on admission (all female subjects).
Who cannot join
- 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 based on medical judgement by the investigator, excluding, for example, simple appendectomy or herniorrhaphy; Estimated glomerular filtration rate < 70 mL/min History of drug hypersensitivity or a presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active; Clinically relevant history of alcoholism or drug abuse in the past 5 years; Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type); Current smokers and those who have smoked within the last 3 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission; Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months; Significant infection or known inflammatory process at screening or admission; Abnormal fundoscopy result at screening; Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission; Use of over the counter medications (including oral natural health products, vitamin and herbal supplements) in the 7 days before the first dose of IMP and use of prescription medications that may affect the safety or other study assessments, in the PI's opinion, are not permitted within 14 days before the first dose of IMP. By exception, acetaminophen/paracetamol ≤ 1 g/day is permitted. Other exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor; Subjects who have previously been enrolled in a BIA 5-1058 study or who have previously been enrolled and dosed in this study; Use of any investigational drug or participation in any clinical trial within 90 days prior to screening; Donation or reception of any blood or blood products within the 3 months prior to screening; Donation or loss of greater than 400 mL of blood within the previous 3 months; Vegetarians, vegans or other medical dietary restrictions; Subjects with a history of cholecystectomy or gall stones; Not able to communicate reliably with the investigator or sub-investigator; Unlikely to co-operate with the requirements of the study; Subjects who are study site employees, or immediate family members of a study site or sponsor employee; Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening; Females of childbearing potential who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and a negative urine pregnancy test at admission); Males with pregnant partners; Failure to satisfy the investigator of fitness to participate for any other reason; Are unwilling or unable to give written informed consent.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Quotient Sciences
Ruddington, Nottingham, NG11 6JS
About this study
Official title: A Double-Blind, Randomised, Placebo-Controlled, Parallel Group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of BIA 5 1058 in Healthy Volunteers
This is a single centre, double-blind, randomised, placebo-controlled, parallel staggered group study of BIA 5-1058 in 11 different cohorts of 15 healthy subjects. Subjects will be randomly assigned to receive once-daily oral doses of BIA 5-1058 or matching placebo for 10 days.
The primary objectives of the study are to assess the safety and tolerability of BIA 5-1058 after repeated ascending doses under fed and fasted conditions and to assess the pharmacokinetics (PK) of BIA 5-1058 after repeated ascending doses under fed conditions having matching fasting cohorts for comparison of bioavailability.
It is planned that comparison cohorts will be dosed in parallel, i.e. Cohorts 1 and 2, 3 and 4, 5 and 6, 7 and 8 and 9 and 10. Cohorts may be split or dosed sequentially for logistical purposes; however, data from both comparison cohorts (e.g. Cohorts 1 and 2) must be available before dose escalation to the next dose levels.
Read the detailed description
Each cohort will follow the same study design. Subjects will be screened for inclusion in the study between 28 and 3 days before the first dose. Eligible subjects will be admitted 2 days before dosing (Day -2) for all regimens, and will remain resident in the clinic until 72 h after the last dose (Day 13). On Day -1, blood samples will be taken in all cohorts for PD assessments at pre-defined time points. These time points will be time matched to Day 1 PK and PD time points. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 (fed cohorts) will also undergo continuous cardiac monitoring via 24 h Holter recordings on Day -1.
Subjects in Cohorts 1, 3, 5, 7 and 9 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1 to Day 10, administered in the morning of each day after a minimum of 8 h fast and will remain fasted until 4 h post-dose. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1 to Day 10, administered in the morning of each day, 30 minutes after the start of a moderate breakfast containing approximately 550 kcal with fat contributing approximately 150 kcal.
- Being tested
- BIA 5-1058, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIA 5-1058Drug
Also called Zamicastat
25 mg and 100 mg tablets; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), BIA 5-1058 will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing.
In Cohorts 2, 4, 6, 8 and 10 (fed), BIA 5-1058 will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal.
Each dose will be administered with 240 mL water.
PlaceboDrug
matching placebo tablet; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), placebo will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing.
In Cohorts 2, 4, 6, 8 and 10 (fed), placebo will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal.
Each dose will be administered with 240 mL water.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (BIA 5-1058 /50 mg/fasted) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 50 mg (as 2 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 2 (BIA 5-1058 /25 mg/fed) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 25 mg (as 1 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 3 (BIA 5-1058 /100 mg/fasted) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 100 mg (as 1 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 4 (BIA 5-1058 /50 mg/fed) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 50 mg (as 2 x 25 mg tablet) or matching placebo 12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 5 (BIA 5-1058 /150 mg/fasted) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 150 mg (as 1 x 100 mg and 2 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 6 (BIA 5-1058 /75 mg/fed) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 75 mg (as 3 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 7 (BIA 5-1058 /200 mg/fasted) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 200 mg (as 2 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 8 (BIA 5-1058 /100 mg/fed) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 100 mg (as 1 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 9 (BIA 5-1058 /400 mg/fasted) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 400 mg (as 4 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 10 (BIA 5-1058 /200 mg/fed) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 200 mg (as 2 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
| Cohort 11 (BIA 5-1058 /400 mg/fed) | Experimental | 15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 400 mg (as 4 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) Receives: Drug: BIA 5-1058; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax: maximum observed concentration
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
Cmin: minimum observed concentration at steady state
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
Tlag: the elapsed time from dosing at which analyte was first quantifiable in a concentration vs time profile
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
Tmax: the time from dosing at which Cmax was apparent
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
AUC(0-t): area under the curve from 0 time to last measurable concentration
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
AUC(0-tau): area under the curve during a dosing interval
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
AUC(0-inf): area under the curve from 0 time extrapolated to infinity
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
AUC%extrap: percentage of AUC(0-inf) extrapolated beyond last measured time point
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
Lambda-z: the slope of the apparent elimination phase
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
t1/2: the apparent elimination half-life
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
Cl/F: clearance, the apparent volume cleared of parent drug per unit time after extravascular administration
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
MRT: mean residence time
PK parameters analysis
Measured: Day 1, Day 6 and Day 10
Secondary outcomes (7)
Emax: maximum observed % change from time-matched baseline
Pharmacodynamic parameters analysis
Measured: Day 1 and Day 10
TEmax: Time of maximum observed % change from time-matched baseline
Pharmacodynamic parameters analysis
Measured: Day 1 and Day 10
EAUC: % change from time-matched baseline area under the curve during a dosing interval
Pharmacodynamic parameters analysis
Measured: Day 1 and Day 10
heart rate levels
Change from pre-submersion in heart rate levels following immersion of hand in ice cold water for 4 min (cold pressor test) - Cohort 9 only
Measured: pre-dose and Day 10
Blood pressure levels
Change from pre-submersion in , blood pressure levels following immersion of hand in ice cold water for 4 min (cold pressor test) - Cohort 9 only
Measured: pre-dose and Day 10
catecholamine (norepinephrine, epinephrine and dopamine) levels
Change from pre-submersion in , catecholamine (norepinephrine, epinephrine and dopamine) levels following immersion of hand in ice cold water for 4 min (cold pressor test) - Cohort 9 only
Measured: pre-dose and Day 10
% inhibition of dopamine ß-hydroxylase (DβH) activity
Measured: Day 1 and Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2018
- Study start28 May 2018
- Primary completion18 Mar 2019
- Study completion18 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular Disease+Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03708146
- Sponsor's protocol ID
- BIA-51058-116
- Other IDs
- 2018-000113-20, 2018
- Status last verified
- Dec 2020
- First submitted
- 12 Oct 2018
- Last updated
- 31 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomised, Placebo-Controlled, Parallel Group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of BIA 5 1058 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03708146
- Acronym / sponsor ID
- BIA-51058-116
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- 28 May 2018 (actual)
- Primary completion
- 18 Mar 2019 (actual)
- Study completion
- 18 Mar 2019 (actual)
- First posted
- 17 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single centre, double-blind, randomised, placebo-controlled, parallel staggered group study of BIA 5-1058 in 11 different cohorts of 15 healthy subjects. Subjects will be randomly assigned to receive once-daily oral doses of BIA 5-1058 or matching placebo for 10 days.
The primary objectives of the study are to assess the safety and tolerability of BIA 5-1058 after repeated ascending doses under fed and fasted conditions and to assess the pharmacokinetics (PK) of BIA 5-1058 after repeated ascending doses under fed conditions having matching fasting cohorts for comparison of bioavailability.
It is planned that comparison cohorts will be dosed in parallel, i.e. Cohorts 1 and 2, 3 and 4, 5 and 6, 7 and 8 and 9 and 10. Cohorts may be split or dosed sequentially for logistical purposes; however, data from both comparison cohorts (e.g. Cohorts 1 and 2) must be available before dose escalation to the next dose levels.
Detailed description
Each cohort will follow the same study design. Subjects will be screened for inclusion in the study between 28 and 3 days before the first dose. Eligible subjects will be admitted 2 days before dosing (Day -2) for all regimens, and will remain resident in the clinic until 72 h after the last dose (Day 13). On Day -1, blood samples will be taken in all cohorts for PD assessments at pre-defined time points. These time points will be time matched to Day 1 PK and PD time points. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 (fed cohorts) will also undergo continuous cardiac monitoring via 24 h Holter recordings on Day -1.
Subjects in Cohorts 1, 3, 5, 7 and 9 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1 to Day 10, administered in the morning of each day after a minimum of 8 h fast and will remain fasted until 4 h post-dose. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1 to Day 10, administered in the morning of each day, 30 minutes after the start of a moderate breakfast containing approximately 550 kcal with fat contributing approximately 150 kcal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (BIA 5-1058 /50 mg/fasted) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 50 mg (as 2 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 2 (BIA 5-1058 /25 mg/fed) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 25 mg (as 1 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 3 (BIA 5-1058 /100 mg/fasted) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 100 mg (as 1 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 4 (BIA 5-1058 /50 mg/fed) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 50 mg (as 2 x 25 mg tablet) or matching placebo 12 active and 3 placebo) |
| Cohort 5 (BIA 5-1058 /150 mg/fasted) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 150 mg (as 1 x 100 mg and 2 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 6 (BIA 5-1058 /75 mg/fed) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 75 mg (as 3 x 25 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 7 (BIA 5-1058 /200 mg/fasted) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 200 mg (as 2 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 8 (BIA 5-1058 /100 mg/fed) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 100 mg (as 1 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 9 (BIA 5-1058 /400 mg/fasted) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 400 mg (as 4 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 10 (BIA 5-1058 /200 mg/fed) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 200 mg (as 2 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
| Cohort 11 (BIA 5-1058 /400 mg/fed) | Experimental | Drug: BIA 5-1058, Drug: Placebo15 Subjects: 12 active and 3 placebo; BIA 5-1058 Tablet 400 mg (as 4 x 100 mg tablet) or matching placebo tablet (12 active and 3 placebo) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Able and willing to comply with the study restrictions and to give written informed consent before any study procedure; Male or non-pregnant, non-lactating female subjects aged 18 to 55 years, inclusive; Body mass index (BMI) between 18.0 and 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator; Healthy as determined by the investigator based on medical history, physical examination, clinical laboratory test results, vital signs (systolic blood pressure ≥ 90 mmHg and ≤ 150 mmHg, diastolic blood pressure ≥ 50 mmHg and ≤ 90 mmHg) and digital 12-lead ECG); 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 Negative screen for alcohol and drugs of abuse at screening and admission Non-smokers or ex-smokers for at least 3 months;
- Male subjects and female partner willing to a condom plus an approved method of effective contraception, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from the time of informed consent until 90 days after last dose of IMP. Male subjects must refrain from donating sperm throughout the study and for 90 days after the last dose of IMP; Female subjects of childbearing potential willing to use, with their partner, a condom and an approved method of highly effective contraception from the time of informed consent until 30 days after the last follow-up visit. Hormonal contraceptives are not permitted for female subjects. Female subjects must not donate ova from the time of the first dose until 90 days after the last dose of study drug; If female, nonchildbearing 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 Negative serum pregnancy test at screening and negative urine pregnancy test on admission (all female subjects).
Key exclusion criteria (1 listed)
- 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 based on medical judgement by the investigator, excluding, for example, simple appendectomy or herniorrhaphy; Estimated glomerular filtration rate < 70 mL/min History of drug hypersensitivity or a presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active; Clinically relevant history of alcoholism or drug abuse in the past 5 years; Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type); Current smokers and those who have smoked within the last 3 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission; Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months; Significant infection or known inflammatory process at screening or admission; Abnormal fundoscopy result at screening; Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission; Use of over the counter medications (including oral natural health products, vitamin and herbal supplements) in the 7 days before the first dose of IMP and use of prescription medications that may affect the safety or other study assessments, in the PI's opinion, are not permitted within 14 days before the first dose of IMP. By exception, acetaminophen/paracetamol ≤ 1 g/day is permitted. Other exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor; Subjects who have previously been enrolled in a BIA 5-1058 study or who have previously been enrolled and dosed in this study; Use of any investigational drug or participation in any clinical trial within 90 days prior to screening; Donation or reception of any blood or blood products within the 3 months prior to screening; Donation or loss of greater than 400 mL of blood within the previous 3 months; Vegetarians, vegans or other medical dietary restrictions; Subjects with a history of cholecystectomy or gall stones; Not able to communicate reliably with the investigator or sub-investigator; Unlikely to co-operate with the requirements of the study; Subjects who are study site employees, or immediate family members of a study site or sponsor employee; Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening; Females of childbearing potential who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and a negative urine pregnancy test at admission); Males with pregnant partners; Failure to satisfy the investigator of fitness to participate for any other reason; Are unwilling or unable to give written informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIA 5-1058Also: Zamicastat25 mg and 100 mg tablets; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), BIA 5-1058 will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing. In Cohorts 2, 4, 6, 8 and 10 (fed), BIA 5-1058 will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal. Each dose will be administered with 240 mL water. | Drug | Cohort 1 (BIA 5-1058 /50 mg/fasted), Cohort 10 (BIA 5-1058 /200 mg/fed), Cohort 11 (BIA 5-1058 /400 mg/fed), Cohort 2 (BIA 5-1058 /25 mg/fed), Cohort 3 (BIA 5-1058 /100 mg/fasted), Cohort 4 (BIA 5-1058 /50 mg/fed), Cohort 5 (BIA 5-1058 /150 mg/fasted), Cohort 6 (BIA 5-1058 /75 mg/fed), Cohort 7 (BIA 5-1058 /200 mg/fasted), Cohort 8 (BIA 5-1058 /100 mg/fed), Cohort 9 (BIA 5-1058 /400 mg/fasted) |
| Placebomatching placebo tablet; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), placebo will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing. In Cohorts 2, 4, 6, 8 and 10 (fed), placebo will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal. Each dose will be administered with 240 mL water. | Drug | Cohort 1 (BIA 5-1058 /50 mg/fasted), Cohort 10 (BIA 5-1058 /200 mg/fed), Cohort 11 (BIA 5-1058 /400 mg/fed), Cohort 2 (BIA 5-1058 /25 mg/fed), Cohort 3 (BIA 5-1058 /100 mg/fasted), Cohort 4 (BIA 5-1058 /50 mg/fed), Cohort 5 (BIA 5-1058 /150 mg/fasted), Cohort 6 (BIA 5-1058 /75 mg/fed), Cohort 7 (BIA 5-1058 /200 mg/fasted), Cohort 8 (BIA 5-1058 /100 mg/fed), Cohort 9 (BIA 5-1058 /400 mg/fasted) |
Primary outcome
Cmax: maximum observed concentration
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
Cmin: minimum observed concentration at steady state
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
Tlag: the elapsed time from dosing at which analyte was first quantifiable in a concentration vs time profile
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
Tmax: the time from dosing at which Cmax was apparent
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
AUC(0-t): area under the curve from 0 time to last measurable concentration
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
AUC(0-tau): area under the curve during a dosing interval
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
AUC(0-inf): area under the curve from 0 time extrapolated to infinity
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
AUC%extrap: percentage of AUC(0-inf) extrapolated beyond last measured time point
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
Lambda-z: the slope of the apparent elimination phase
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
t1/2: the apparent elimination half-life
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
Cl/F: clearance, the apparent volume cleared of parent drug per unit time after extravascular administration
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
MRT: mean residence time
Time frame: Day 1, Day 6 and Day 10
PK parameters analysis
7 secondary outcomes
Emax: maximum observed % change from time-matched baseline
Time frame: Day 1 and Day 10
TEmax: Time of maximum observed % change from time-matched baseline
Time frame: Day 1 and Day 10
EAUC: % change from time-matched baseline area under the curve during a dosing interval
Time frame: Day 1 and Day 10
heart rate levels
Time frame: pre-dose and Day 10
Blood pressure levels
Time frame: pre-dose and Day 10
catecholamine (norepinephrine, epinephrine and dopamine) levels
Time frame: pre-dose and Day 10
% inhibition of dopamine ß-hydroxylase (DβH) activity
Time frame: Day 1 and Day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIA 5-1058 in people with Cardiovascular Disease+Pulmonary Disease and Pulmonary Arterial Hypertension, run by Bial - Portela C S.A. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax: maximum observed concentration (time frame: Day 1, Day 6 and Day 10). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2020.