Hypertension and Chronic Heart FailurePhase 1NCT02151994
Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058.
A Phase 1 study testing BIA 5-1058 in people with Hypertension and Chronic Heart Failure, run by Bial - Portela C S.A. at 1 site in Netherlands.
Trial summary
The purpose of this study is to to assess the safety and tolerability of BIA 5 1058 after single and multiple oral doses Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypertension and Chronic Heart Failure
- 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
- 124 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2011to Jan 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects were eligible for the study if they met all the following inclusion criteria:
- Gender - male
- Age - 18 - 55 years, inclusive
- Body Mass Index (BMI) - 18.0 - 30.0 kg m2 (BMI (kg m2) = Body weight (kg) - Heigh t2 (m 2))
- Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, power drinks), grapefruit (juice) and tobacco products from 48 h prior to entry in the clinical research centre until discharge
- Medical history without major pathology
Show all 10Show fewer
- Normal resting supine blood pressure and pulse rate showing no clinically relevant deviations as judged by the MI
- Computerised (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the MI
- All values for haematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the MI
- Willingness to sign the written ICF
Who cannot join
- Subjects were excluded from participation if any of the following exclusion criteria applied
- Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, haematological, neurologic, or psychiatric disease
- An automatic ECG QTc interval reading at screening or enrolment of + 440 ms.
- Evidence of clinically relevant pathology
- Mental handicap
- History of relevant drug and or food allergies
Show all 21Show fewer
- Smoking more than 10 cigarettes and or cigars and or pipes daily
- History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
- Use of any prescription drug within 30 days before study drug administration with the exception of influenza vaccination
- Use of any over-the-counter drugs including health supplements, herbal supplements such as St. John's Wort extract (except for the occasional use of acetaminophen (paracetamol), aspirin and vitamins - 100 recommended daily allowance) within 7 days before study drug administration. The use of paracetamol and or topical medication was allowed up to 3 days before entrance into the clinical research facility
- Participation in a drug study within 90 days prior to drug administration
- Participation in more than 3 other drug studies in the 10 months preceding the start of this study (this was the first administration of study drug)
- Donation of more than 50 mL of blood within 90 days prior to first drug administration
- Donation of more than 1.5 litres of blood in the 10 months preceding the start of this study (this was the first administration of study drug)
- Positive screen on drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids), barbiturates, benzodiazepines, tricyclic antidepressants and alcohol
- Intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)
- Positive screen on hepatitis B surface antigen (HBsAg)
- Positive screen on anti hepatitis C virus (HCV)
- Positive screen on anti human immunodeficiency virus (HIV) 1 - 2
- Acute disease state indicated as clinically relevant by the MI (e.g. nausea, vomiting, fever, diarrhoea) within 7 days before the first drug administration
- Non-willingness to consume the Food and Drug Administration (FDA) breakfast (FE part only)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-blind, Randomised, Placebo-controlled, Combined Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058, in Healthy Male Volunteers
The purpose of this study is to to assess the safety and tolerability of BIA 5 1058 after single and multiple oral doses
Read the detailed description
This was a Phase 1, double blind, randomised, placebo-controlled combined single ascending dose (SAD), including food interaction (food effect, FE) analysis, and multiple ascending dose (MAD) study.
SAD: This part consisted of an eligibility screening period, one study period involving administration of single doses of BIA 5-1058 or placebo according to a randomized design, and a follow-up period. Nine sequential groups of 8 healthy young male subjects were dosed. Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo. In this first-in-human study, the subjects participating at the lowest dose level of 5 mg were dosed according to a sentinel dosing design to ensure optimal safety. Initially, 2 subjects were dosed; 1 subject with BIA 5-1058 and 1 subject with placebo. After the safety and tolerability results of the first 24 h following dosing for the initial subjects had been found to be acceptable to the MI, the other 6 subjects of the lowest dose level were dosed.
MAD: This part consisted of an eligibility screening period, one study period involving administration of multiple doses of BIA 5-1058 or placebo once daily for 10 days, and a follow-up period. Five sequential groups of 8 healthy young male subjects were dosed.
Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo.
The starting dose of 50 mg was chosen taking into consideration the dose range of the previous SAD sequential groups and was approved by the IEC. Escalation to the next higher dose and the determination of the next dose level was based on safety, tolerability and available PK results of the previously administered dose
FE: This part consisted of an eligibility screening period, an open-label two-way crossover study period, and a follow-up period. One group of 12 subjects received single doses of 400 mg BIA 5-1058 during 2 treatment periods, once after having fasted overnight and once after consumption of a high fat breakfast. Each treatment was separated by a period of at least 7 days. The treatment sequence was determined by randomisation.
- Conditions
- Hypertension and Chronic Heart Failure
- Being tested
- BIA 5-1058, Placebo
- Keywords
- BIA 5-1058, hypertension, chronic heart failure, cardiovascular disorders
- Medical subject headings
- Hypertension, Cardiovascular Diseases
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
oral administration
PlaceboDrug
oral administration
| Study group | Role | What they receive |
|---|---|---|
| BIA 5-1058 | Experimental | BIA 5-1058 (5, 25 and 100 mg) tablets Receives: Drug: BIA 5-1058 |
| Placebo | Placebo comparator | tablets, visually matching active medication Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Single Ascending Dose (SAD) Period
Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".
Measured: Just before drug administration and twice daily until 72 h after (last) drug administration
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Multiple Ascending Dose (MAD) Period
Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".
Measured: Just before drug administration and twice daily until 72 h after (last) drug administration
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Food Effect (FE)
Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".
Measured: Just before drug administration and twice daily until 72 h after (last) drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study startMar 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypertension and Chronic Heart FailureStudies 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 124 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
- NCT02151994
- Sponsor's protocol ID
- BIA-51058-101
- Status last verified
- Nov 2015
- First submitted
- 26 May 2014
- Last updated
- 5 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomised, Placebo-controlled, Combined Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058, in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT02151994
- Acronym / sponsor ID
- BIA-51058-101
- Conditions
- Hypertension and Chronic Heart Failure
- Keywords
- BIA 5-1058, hypertension, chronic heart failure, cardiovascular disorders
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 2 Jun 2014 (estimated)
- Results
- Posted 5 Jan 2016
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 is to to assess the safety and tolerability of BIA 5 1058 after single and multiple oral doses
Detailed description
This was a Phase 1, double blind, randomised, placebo-controlled combined single ascending dose (SAD), including food interaction (food effect, FE) analysis, and multiple ascending dose (MAD) study.
SAD: This part consisted of an eligibility screening period, one study period involving administration of single doses of BIA 5-1058 or placebo according to a randomized design, and a follow-up period. Nine sequential groups of 8 healthy young male subjects were dosed. Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo. In this first-in-human study, the subjects participating at the lowest dose level of 5 mg were dosed according to a sentinel dosing design to ensure optimal safety. Initially, 2 subjects were dosed; 1 subject with BIA 5-1058 and 1 subject with placebo. After the safety and tolerability results of the first 24 h following dosing for the initial subjects had been found to be acceptable to the MI, the other 6 subjects of the lowest dose level were dosed.
MAD: This part consisted of an eligibility screening period, one study period involving administration of multiple doses of BIA 5-1058 or placebo once daily for 10 days, and a follow-up period. Five sequential groups of 8 healthy young male subjects were dosed.
Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo.
The starting dose of 50 mg was chosen taking into consideration the dose range of the previous SAD sequential groups and was approved by the IEC. Escalation to the next higher dose and the determination of the next dose level was based on safety, tolerability and available PK results of the previously administered dose
FE: This part consisted of an eligibility screening period, an open-label two-way crossover study period, and a follow-up period. One group of 12 subjects received single doses of 400 mg BIA 5-1058 during 2 treatment periods, once after having fasted overnight and once after consumption of a high fat breakfast. Each treatment was separated by a period of at least 7 days. The treatment sequence was determined by randomisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BIA 5-1058 | Experimental | Drug: BIA 5-1058BIA 5-1058 (5, 25 and 100 mg) tablets |
| Placebo | Placebo comparator | Drug: Placebotablets, visually matching active medication |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Gender - male
- Age - 18 - 55 years, inclusive
- Body Mass Index (BMI) - 18.0 - 30.0 kg m2 (BMI (kg m2) = Body weight (kg) - Heigh t2 (m 2))
- Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, power drinks), grapefruit (juice) and tobacco products from 48 h prior to entry in the clinical research centre until discharge
- Medical history without major pathology
Key exclusion criteria (21 listed)
- Subjects were excluded from participation if any of the following exclusion criteria applied
- Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, haematological, neurologic, or psychiatric disease
- An automatic ECG QTc interval reading at screening or enrolment of + 440 ms.
- Evidence of clinically relevant pathology
- Mental handicap
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: Zamicastatoral administration | Drug | BIA 5-1058 |
| Placebooral administration | Drug | Placebo |
Primary outcome
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Single Ascending Dose (SAD) Period
Time frame: Just before drug administration and twice daily until 72 h after (last) drug administration
Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Multiple Ascending Dose (MAD) Period
Time frame: Just before drug administration and twice daily until 72 h after (last) drug administration
Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Food Effect (FE)
Time frame: Just before drug administration and twice daily until 72 h after (last) drug administration
Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hypertension and Chronic Heart Failure
Not yet recruiting
Community Health Worker Nutrition Self-Management Support for Cardio-Kidney-Metabolic Health
Hypertension (HTN), CKD - Chronic Kidney Disease
Recruiting
Vasopressor Agents in Pulmonary Hypertension Crisis
Pulmonary Arterial Hypertension (PAH), Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Not yet recruiting
A Cluster-Randomized Controlled Trial
Hypertension, Stroke
RecruitingPhase 1
: Vascular Function in Health and Disease
Chronic Obstructive Pulmonary Disease, Pulmonary Artery Hypertension
Recruiting
Improving the Collaborative Health of Adult Dyads
Cardiovascular Diseases, Chronic Kidney Diseases
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 Hypertension and Chronic Heart Failure, run by Bial - Portela C S.A. at 1 site in Netherlands.
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 10 inclusion and 21 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 5 Jan 2016. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 5 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Single Ascending Dose (SAD) Period (time frame: Just before drug administration and twice daily until 72 h after (last) drug administration). The study lists 3 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 5 Jan 2016.