Back to resultsTolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453
Primary Purpose
Hypertension, Chronic Heart Failure
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
BIA 5-453
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension
Eligibility Criteria
Inclusion Criteria:
- A signed and dated informed consent form before any study-specific screening procedure was performed.
- Aged between 18 and 45 years, inclusive.
- 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).
- Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Must have been able to abstain from smoking during the inpatient stay.
- Have a high probability for compliance with and completion of the study.
Exclusion Criteria:
Medical History
- Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, haematological, neurologic, or psychiatric disease.
- Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study day 1.
- 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.
Physical and Laboratory Findings
- An automatic ECG QTc interval reading at screening or enrolment >450 ms.
- 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 (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
Prohibited treatments
- Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product (IMP) administration.
- 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 72 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 IMP administration.
- Donation of blood (ie 450 ml) within 90 days before study day 1.
Sites / Locations
- Biotrial
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
2 mg or placebo
10 mg or placebo
20 mg or placebo
50 mg or placebo
100 mg or placebo
200 mg or placebo
400 mg or placebo
600 mg or placebo
900 mg or placebo
1200 mg or placebo
Arm Description
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
BIA 5-453 or placebo
Outcomes
Primary Outcome Measures
Maximum observed plasma concentration (Cmax)
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Time to reach Cmax (Tmax)
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Area under the plasma concentration-time curve from time 0 to the infinity (AUC0-∞)
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
% of subjects with at least one adverse event
Adverse events were continuously monitored from screening until the follow-up visit.
% of subjects by dose group with at least one treatment-emergent adverse event (TEAEs)
Treatment emergent adverse events (TEAE) were defined as adverse events which did not exist before dosing and appeared in the 72 hours following treatment administration or which was present before administration and worsened in the 72 hours following treatment administration.
Apparent terminal elimination half-life (t1/2)
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02845037
Brief Title
Tolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453
Official Title
A Rising Single Oral Dose Study to Investigate the Tolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453 in Healthy Male Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
September 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bial - Portela C S.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety and tolerability of BIA 5-453 after single oral doses
Detailed Description
Single centre, randomised, double-blind, placebo-controlled study of single ascending doses in 10 sequential groups of 8 healthy young male volunteers. Within each group (n=8), 6 volunteers were randomised to receive BIA 5-453 and the remaining 2 volunteers were randomised to receive placebo. A volunteer participated only in a single period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Chronic Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
2 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
10 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
20 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
50 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
100 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
200 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
400 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
600 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
900 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Arm Title
1200 mg or placebo
Arm Type
Experimental
Arm Description
BIA 5-453 or placebo
Intervention Type
Drug
Intervention Name(s)
BIA 5-453
Other Intervention Name(s)
Etamicastat
Intervention Description
BIA 5-453 Gelatine capsule for oral administration (1, 10 or 20 mg). Single oral doses of BIA 4-543 2 mg, 10 mg, 20 mg, 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 900 mg and 1200 mg were administered to subjects in fasting conditions.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Gelatine capsule
Intervention Description
Placebo Gelatine capsule for oral administration. The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient (API).
Primary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax)
Description
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Time Frame
Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Title
Time to reach Cmax (Tmax)
Description
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Time Frame
Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Title
Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)
Description
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Time Frame
Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Title
Area under the plasma concentration-time curve from time 0 to the infinity (AUC0-∞)
Description
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Time Frame
Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
Title
% of subjects with at least one adverse event
Description
Adverse events were continuously monitored from screening until the follow-up visit.
Time Frame
through study completion, an average of 72 hours
Title
% of subjects by dose group with at least one treatment-emergent adverse event (TEAEs)
Description
Treatment emergent adverse events (TEAE) were defined as adverse events which did not exist before dosing and appeared in the 72 hours following treatment administration or which was present before administration and worsened in the 72 hours following treatment administration.
Time Frame
through study completion, an average of 72 hours
Title
Apparent terminal elimination half-life (t1/2)
Description
Mean BIA 5-453 plasma pharmacokinetic parameters ± SD following single doses of 2, 10, 20, 50, 100, 200, 400, 600, 900 and 1200 mg of BIA 5-453 in 10 groups of 6 healthy volunteers each
Time Frame
Day 1 pre-dose then at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60, and 72 hours post-dose
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
A signed and dated informed consent form before any study-specific screening procedure was performed.
Aged between 18 and 45 years, inclusive.
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).
Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Must have been able to abstain from smoking during the inpatient stay.
Have a high probability for compliance with and completion of the study.
Exclusion Criteria:
Medical History
Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, haematological, neurologic, or psychiatric disease.
Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study day 1.
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.
Physical and Laboratory Findings
An automatic ECG QTc interval reading at screening or enrolment >450 ms.
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 (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
Prohibited treatments
Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product (IMP) administration.
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 72 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 IMP administration.
Donation of blood (ie 450 ml) within 90 days before study day 1.
Facility Information:
Facility Name
Biotrial
City
Rennes
ZIP/Postal Code
F-35000
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Tolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453
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