Pulmonary Arterial HypertensionPhase 1NCT04675944
Effect of BIA 5-1058 on the Steady State Pharmacokinetics of Treprostinil
A Phase 1 study testing BIA 5-1058 and treprostinil in people with Pulmonary Arterial Hypertension, run by Bial - Portela C S.A. at 1 site in Germany.
Trial summary
The purpose of this study is to assess the effect of BIA 5-1058 200 mg on the pharmacokinetic (PK) of treprostinil Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- BIA 5-1058 and treprostinil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 28 Feb 2018to 25 May 2018
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provided a signed and dated informed consent before any study specific procedures were conducted.
- Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit.
- Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error.
- Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit.
- Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period.
- Negative test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBc), immunoglobulin M (IgM) anti-HBc, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus (HIV) (Types 1 and 2) antibodies at the Screening Visit.
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- Negative screen for alcohol and drugs of abuse at the Screening Visit and on admission to each treatment period.
- Subject had to be willing and able to be confined to the clinical unit and had to adhere to the study and lifestyle restrictions.
- Contraception requirements:
- Male subjects had to use together with his female partner/spouse a highly effective contraception form of birth control in combination with a barrier method throughout the clinical study period and agreed not to father a child or to donate sperm starting at the Screening Visit and throughout the clinical study.
- Female subjects had to either be of non childbearing potential or had to use highly effective methods of contraception from at least 3 months before the Screening Visit and throughout the clinical study in combination with a barrier method.
- Subjects who met the following criteria were considered eligible to participate/continue in the study:
- Provided a signed and dated informed consent before any study specific procedures were conducted.
- Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit.
- Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error.
- Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit.
- Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period.
- Negative test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti HBc), immunoglobulin M (IgM) anti-HBc, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus (HIV) (Types 1 and 2) antibodies at the Screening Visit.
- Negative screen for alcohol and drugs of abuse at the Screening Visit and on admission to each treatment period.
- Subject had to be willing and able to be confined to the clinical unit and had to adhere to the study and lifestyle restrictions.
- Contraception requirements:
- Male subjects had to use together with his female partner/spouse a highly effective contraception form of birth control in combination with a barrier method throughout the clinical study period and agreed not to father a child or to donate sperm starting at the Screening Visit and throughout the clinical study.
- Female subjects had to either be of non childbearing potential or had to use highly effective methods of contraception from at least 3 months before the Screening Visit and throughout the clinical study in combination with a barrier method.
Who cannot join
- Subjects that met any of the following criteria were not considered eligible to participate/continue in the study:
- Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue disease or disorders within 5 years before the first investigational medicinal product (IMP) administration.
- Documented coronary artery disease (any of prior myocardial infarction, positive stress test, positive nuclear perfusion study, prior coronary artery bypass graft [CABG] surgery or percutaneous coronary intervention, angiogram showing at least 75% stenosis in a major coronary artery), acute coronary syndrome or current symptoms of myocardial ischemia and angina.
- Clinically relevant surgical history that involved the stomach and/or intestinal system, potentially affecting absorption of IMPs.
- Any clinically relevant findings in the laboratory tests, particularly any abnormality in the coagulation tests or the liver function tests, as judged by the Principal Investigator, at the Screening Visit and on admission to each treatment period. If a laboratory assessment was outside of the reference range at the local laboratory at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out laboratory error.
- Subjects with alanine aminotransferase (ALT) > 1.0 x the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) > 1.0 x ULN and/or total bilirubin > 1.0 x ULN (isolated bilirubin > 1.0 x ULN and ≤ 1.5 x ULN was acceptable if bilirubin was fractionated and direct bilirubin < 35%), as confirmed by subsequent repeat assessment, at the Screening Visit and on admission to each treatment period.
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- History of relevant atopy or drug hypersensitivity.
- History of alcoholism or drug abuse.
- History of drinking > 24 g (males) and > 12 g (females) of pure alcohol per day (10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 3 months before first admission to the clinical unit.
- Use of alcohol within 72 hours before the Screening Visit and from 48 hours before dosing until completion of the Follow-up Visit.
- Significant infection or known inflammatory process at the Screening Visit or upon admission to all Treatment Periods, as judged by the Principal Investigator.
- Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of the Screening Visit or upon admission to all treatment periods.
- Subjects with blood pressure (BP) measurements (mean of triplicate) outside the ranges, at the Screening Visit or admission to the first treatment period:
- Systolic blood pressure (SBP) < 100 mmHg or > 140 mmHg
- Diastolic blood pressure (DBP) < 60 mmHg or > 90 mmHg
- 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, at the Screening Visit or admission to the first treatment Period.
- Abnormal fundoscopy.
- Electrocardiogram (mean of triplicate) with corrected QT interval using the Fridericia's formula (QTcF) > 450 ms at the Screening Visit or admission to the first treatment period.
- Having an estimated glomerular filtration rate (eGFR) < 90 mL/min, based on creatinine clearance calculation by the Cockcroft Gault formula and normalized to an average surface area of 1.73m2.
- Previous use of BIA 5 1058.
- Use of any investigational drug or participation in any clinical study within 60 days or 5 half life times, whichever was longer, before the first administration of IMP.
- Having received IMP in more than 3 studies within 12 months before the Screening Visit.
- Donated or received blood within 56 days before first administration of IMP.
- Donated or received plasma within 30 days before first administration of IMP.
- History of any significant bleeding within the last 56 days prior to first administration of IMP.
- Vegetarians, vegans or other medical dietary restrictions.
- Not able to communicate reliably with the Principal Investigator.
- Unlikely to comply with the requirements of the study.
- Use of over the counter (OTC) medications (including oral natural health products, vitamin, and herbal supplements) within 7 days before the first IMP administration until the Follow up Visit.
- Use of prescription medications that could have affected the safety or other study assessments, in the Principal Investigator's opinion, within 14 days before the first IMP administration until the Follow-up Visit. By exception, acetaminophen/paracetamol -1000 mg/day was permitted.
- CYP2B6, CYP2C8, CYP2D6, CYP3A4 (BIA 5-1058 metabolism) and CYP2C9, CYP2C8 (treprostinil metabolism): use of inhibitors taken within 7 days before the first IMP administration and inducers taken within 28 days before first IMP administration.
- Any known allergy or contraindication to any of the IMPs or their content.
- The subject was an employee or the close relative of an employee of the Sponsor or the Contract Research Organization (CRO) involved in the clinical study.
- Vulnerable subjects, e.g., subjects kept in detention, protected adults under guardianship, trusteeship and soldiers or subjects committed to an institution by governmental or juridical order.
- If female:
- Pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Three Period, Fixed Sequence Study to Assess the Effect of a Single Dose of BIA 5 1058 200 mg on the Steady State Pharmacokinetics of Treprostinil in Healthy Subjects Under Fed Conditions
The purpose of this study is to assess the effect of BIA 5-1058 200 mg on the pharmacokinetic (PK) of treprostinil
Read the detailed description
This study was an open-label, three period, fixed sequence study in healthy male and female subjects performed at a single study center.
The study comprised:
- Screening during Days -28 to -2 (both inclusive).
- Three treatment periods separated by a washout period of at least 10 days.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- BIA 5-1058, treprostinil
- 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
200 mg (2 x 100 mg tablets), oral route
treprostinilDrug
Also called Orenitram
1 mg (1 extended-release tablet), oral route
| Study group | Role | What they receive |
|---|---|---|
| BIA 5-1058 / treprostinil | Experimental | Three treatment periods separated by a washout period of at least 10 days Receives: Drug: BIA 5-1058; Drug: treprostinil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration - Cmax
Primary Pharmacokinetic Parameters - BIA 5 1058
Measured: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours
Area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration - AUC0-t
Primary Pharmacokinetic Parameters - BIA 5 1058
Measured: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours
AUC from time zero extrapolated to infinity - AUC0-inf
Primary Pharmacokinetic Parameters - BIA 5 1058
Measured: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours
Maximum observed plasma concentration at steady state - Cmax,ss
Primary Pharmacokinetic Parameters - Treprostinil
Measured: Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours.
AUC over the dosing interval at steady state - AUC0-τ,ss
Primary Pharmacokinetic Parameters - Treprostinil
Measured: Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2020
- Study start28 Feb 2018
- Primary completion25 May 2018
- Study completion25 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial 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
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT04675944
- Sponsor's protocol ID
- BIA-51058-106
- Other IDs
- 2017-000245-43, 2017
- Status last verified
- Dec 2020
- First submitted
- 15 Dec 2020
- Last updated
- 19 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 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Three Period, Fixed Sequence Study to Assess the Effect of a Single Dose of BIA 5 1058 200 mg on the Steady State Pharmacokinetics of Treprostinil in Healthy Subjects Under Fed Conditions
- ClinicalTrials.gov ID
- NCT04675944
- Acronym / sponsor ID
- BIA-51058-106
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- 28 Feb 2018 (actual)
- Primary completion
- 25 May 2018 (actual)
- Study completion
- 25 May 2018 (actual)
- First posted
- 19 Dec 2020 (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 is to assess the effect of BIA 5-1058 200 mg on the pharmacokinetic (PK) of treprostinil
Detailed description
This study was an open-label, three period, fixed sequence study in healthy male and female subjects performed at a single study center.
The study comprised:
- Screening during Days -28 to -2 (both inclusive).
- Three treatment periods separated by a washout period of at least 10 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BIA 5-1058 / treprostinil | Experimental | Drug: BIA 5-1058, Drug: treprostinilThree treatment periods separated by a washout period of at least 10 days |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- Provided a signed and dated informed consent before any study specific procedures were conducted.
- Male and female subjects aged 18 to 45 years (both inclusive) at the Screening Visit.
- Healthy as determined by the Principal Investigator based on medical history, physical examination, clinical laboratory test results, vital signs and digital 12 lead electrocardiogram (ECG). If a vital sign or ECG assessment was outside of the reference range at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out any error.
- Non-smoker or ex-smoker for at least 3 months prior to the Screening Visit.
- Body mass index (BMI) between 18.5 and 29.9 kg/m2 (both inclusive) at the Screening Visit and on admission to each treatment period.
Key exclusion criteria (36 listed)
- Subjects that met any of the following criteria were not considered eligible to participate/continue in the study:
- Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue disease or disorders within 5 years before the first investigational medicinal product (IMP) administration.
- Documented coronary artery disease (any of prior myocardial infarction, positive stress test, positive nuclear perfusion study, prior coronary artery bypass graft [CABG] surgery or percutaneous coronary intervention, angiogram showing at least 75% stenosis in a major coronary artery), acute coronary syndrome or current symptoms of myocardial ischemia and angina.
- Clinically relevant surgical history that involved the stomach and/or intestinal system, potentially affecting absorption of IMPs.
- Any clinically relevant findings in the laboratory tests, particularly any abnormality in the coagulation tests or the liver function tests, as judged by the Principal Investigator, at the Screening Visit and on admission to each treatment period. If a laboratory assessment was outside of the reference range at the local laboratory at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrolment to rule out laboratory error.
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: Zamicastat200 mg (2 x 100 mg tablets), oral route | Drug | BIA 5-1058 / treprostinil |
| treprostinilAlso: Orenitram1 mg (1 extended-release tablet), oral route | Drug | BIA 5-1058 / treprostinil |
Primary outcome
Maximum observed plasma concentration - Cmax
Time frame: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours
Primary Pharmacokinetic Parameters - BIA 5 1058
Area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration - AUC0-t
Time frame: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours
Primary Pharmacokinetic Parameters - BIA 5 1058
AUC from time zero extrapolated to infinity - AUC0-inf
Time frame: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours
Primary Pharmacokinetic Parameters - BIA 5 1058
Maximum observed plasma concentration at steady state - Cmax,ss
Time frame: Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours.
Primary Pharmacokinetic Parameters - Treprostinil
AUC over the dosing interval at steady state - AUC0-τ,ss
Time frame: Pre-last dose (Treatment Period 2, Day 6 and Treatment Period 3, Day 6) and post-last dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours.
Primary Pharmacokinetic Parameters - Treprostinil
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 19 Dec 2020.
- Individual participant dataSharing planned: Undecided
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A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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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 and treprostinil in people with Pulmonary Arterial Hypertension, run by Bial - Portela C S.A. at 1 site in Germany.
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 23 inclusion and 36 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 19 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 Germany. 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 (time frame: Pre-dose (Treatment Period 1, Day 1 and Treatment Period 3, Day 6) and post-dose at 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60 and 72 hours). The study lists 5 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 19 Dec 2020.