HypertensionPhase 1NCT03090724
Pharmacokinetics of BIA 5-453 and Its Metabolites
A Phase 1 study testing BIA 5-453 in people with Hypertension and Chronic Heart Failure, run by Bial - Portela C S.A. at 1 site in France.
Trial summary
The purpose of this study was to assess the effects of age on the pharmacokinetic (PK) profile of BIA 5-453 and its metabolites. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Chronic Heart Failure
- What is being tested?
- BIA 5-453
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 13 Jun 2008to 12 Aug 2008
- 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 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All subjects (young and elderly):
- A signed and dated informed consent form before any study-specific screening procedure is performed.
- Healthy 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 smoker of <10 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
- Young subjects only:
- Males aged between 18 and 45 years, inclusive.
- Elderly subjects only:
- Males older than 65 years, inclusive. Specific inclusion criteria procedure: genotyping Since acetylation is an important BIA 5-453 metabolic pathway, NAT1 and NAT2 genotyping was required for inclusion for distinguishing between poor and faster acetylators (both could however be enrolled in the study).
Who cannot join
- All subjects (young and elderly):
- General
- Subjects who had participated in a clinical trial with an investigational drug within the 90 days prior to screening.
- Subjects who were likely to be noncompliant with the protocol, or who were felt to be unsuitable by the Investigator for any other reason.
- Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
- Positive findings of urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
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- Medical History
- Any significant cardiovascular, hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes), immunological, dermatological, haematological, neurological, or psychiatric disease and history thereof.
- Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study Day 1.
- Subjects proned to orthostatic hypotension: there was a measurement of supine blood pressure (BP) and heart rate (HR) after the subjects had been resting for at least 10 minutes, followed by standing BP and HR after 2 minutes of standing: orthostatic hypotension as defined by as a difference between supine systolic BP (SBP) and standing SBP ≥20 mmHg or a difference between supine diastolic BP (DBP) and standing DBP ≥10 mmHg.
- History of drug abuse within 1 year before study day 1.
- History of alcoholism within 1 year before day 1. Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° [10%] wine = 12 g; 4 cL of aperitif, 42° [42%] whiskey = 17 g; 25 cL glass of 3° [3%] beer = 7.5 g; 25 cL glass of 6° [6%] beer = 15 g.
- History of any clinically important drug allergy.
- Had previously received BIA 5-453. Prohibited treatments and dietary restrictions
- Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 24 hours before study day 1.
- Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen [paracetamol], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before BIA 5-453 administration.
- Donation of blood (i.e. 450 mL) within 60 days before study day 1.
- Young subjects only:
- General
- An automatic QTc interval reading ≥450 ms at the screening assessment. Prohibited treatments and dietary restrictions
- Prohibited Treatments: use of any investigational drug within 90 days (young and elderly subjects) or prescription drug within 30 days before BIA 5-453 administration.
- Elderly subjects only:
- General
- An automatic QTc interval reading ≥470 ms at the screening assessment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single-dose and Steady-state Pharmacokinetics of BIA 5-453 and Its Metabolites in Healthy Male Elderly Subjects Compared With Those in Healthy Male Young Subjects
The purpose of this study was to assess the effects of age on the pharmacokinetic (PK) profile of BIA 5-453 and its metabolites.
Read the detailed description
Single-centre, open-label, parallel group, non-randomised study in 12 healthy elderly and 12 healthy younger male subjects, who participated in 2 consecutive phases:
Phase A: a single-dose phase (including a wash out period); Phase B: a multiple-dose phase during 7 days (steady state).
- Conditions
- Hypertension, Chronic Heart Failure
- Being tested
- BIA 5-453
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIA 5-453Drug
Also called Etamicastat
100 mg of BIA 5-453 (combination of two 50 mg capsules); Oral, once-daily (QD), in the morning in fasting conditions
| Study group | Role | What they receive |
|---|---|---|
| BIA 5-453 (Young) | Experimental | Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration.
Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state) Receives: Drug: BIA 5-453 |
| BIA 5-453 (Elderly) | Experimental | Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration.
Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state) Receives: Drug: BIA 5-453 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax) - DAY 1
Measured: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The time at which Cmax was observed (Tmax) - Day 1
Measured: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The terminal half-life (t1/2) - Day 1
Measured: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The area under the concentration-time curve from 0 to infinity (AUC0-∞) - Day 1
Measured: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The Area Under the Curve from time 0 to 24 h post-dose (AUC0-24) - Day 1
Measured: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
Maximum observed plasma concentration (Cmax) - DAY 12
Measured: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The time at which Cmax was observed (Tmax) - Day 12
Measured: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The terminal half-life (t1/2) - Day 12
Measured: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The area under the concentration-time curve from 0 to infinity (AUC0-∞) - Day 12
Measured: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The Area Under the Curve from time 0 to 24 h post-dose (AUC0-24) - Day 12
Measured: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start13 Jun 2008
- Primary completion12 Aug 2008
- Study completion12 Aug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 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
- NCT03090724
- Sponsor's protocol ID
- BIA-5453-105
- Status last verified
- Mar 2017
- First submitted
- 20 Mar 2017
- Last updated
- 27 Mar 2017
- 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 27 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-dose and Steady-state Pharmacokinetics of BIA 5-453 and Its Metabolites in Healthy Male Elderly Subjects Compared With Those in Healthy Male Young Subjects
- ClinicalTrials.gov ID
- NCT03090724
- Acronym / sponsor ID
- BIA-5453-105
- Conditions
- Hypertension, Chronic Heart Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- 13 Jun 2008 (actual)
- Primary completion
- 12 Aug 2008 (actual)
- Study completion
- 12 Aug 2008 (actual)
- First posted
- 27 Mar 2017 (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.
The purpose of this study was to assess the effects of age on the pharmacokinetic (PK) profile of BIA 5-453 and its metabolites.
Detailed description
Single-centre, open-label, parallel group, non-randomised study in 12 healthy elderly and 12 healthy younger male subjects, who participated in 2 consecutive phases:
Phase A: a single-dose phase (including a wash out period); Phase B: a multiple-dose phase during 7 days (steady state).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BIA 5-453 (Young) | Experimental | Drug: BIA 5-453Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration. Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state) |
| BIA 5-453 (Elderly) | Experimental | Drug: BIA 5-453Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration. Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- A signed and dated informed consent form before any study-specific screening procedure is performed.
- Healthy 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 smoker of <10 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
- Males aged between 18 and 45 years, inclusive.
- Males older than 65 years, inclusive. Specific inclusion criteria procedure: genotyping Since acetylation is an important BIA 5-453 metabolic pathway, NAT1 and NAT2 genotyping was required for inclusion for distinguishing between poor and faster acetylators (both could however be enrolled in the study).
Key exclusion criteria (24 listed)
- General
- Subjects who had participated in a clinical trial with an investigational drug within the 90 days prior to screening.
- Subjects who were likely to be noncompliant with the protocol, or who were felt to be unsuitable by the Investigator for any other reason.
- Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
- Positive findings of urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
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 5-453Also: Etamicastat100 mg of BIA 5-453 (combination of two 50 mg capsules); Oral, once-daily (QD), in the morning in fasting conditions | Drug | BIA 5-453 (Elderly), BIA 5-453 (Young) |
Primary outcome
Maximum observed plasma concentration (Cmax) - DAY 1
Time frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The time at which Cmax was observed (Tmax) - Day 1
Time frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The terminal half-life (t1/2) - Day 1
Time frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The area under the concentration-time curve from 0 to infinity (AUC0-∞) - Day 1
Time frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
The Area Under the Curve from time 0 to 24 h post-dose (AUC0-24) - Day 1
Time frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
Maximum observed plasma concentration (Cmax) - DAY 12
Time frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The time at which Cmax was observed (Tmax) - Day 12
Time frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The terminal half-life (t1/2) - Day 12
Time frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The area under the concentration-time curve from 0 to infinity (AUC0-∞) - Day 12
Time frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
The Area Under the Curve from time 0 to 24 h post-dose (AUC0-24) - Day 12
Time frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
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 27 Mar 2017.
- 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 5-453 in people with Hypertension and Chronic Heart Failure, run by Bial - Portela C S.A. at 1 site in France.
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 8 inclusion and 24 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 27 Mar 2017. 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 France. 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?
Maximum observed plasma concentration (Cmax) - DAY 1 (time frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose). The study lists 10 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 27 Mar 2017.