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Completed

NCT Number: NCT02845037

Tolerability, Pharmacokinetics and Dopamine ß-hydroxylase (DßH) Inhibition Profile of BIA 5-453

The purpose of this study is to assess the safety and tolerability of BIA 5-453 after single oral doses

Completed

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Key information

Conditions

Hypertension Cardiovascular Diseases Chronic Heart Failure Vascular Diseases

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Biotrial

Rennes, F-35000, France

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BIA 5-453

Drug

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.

Other names: Etamicastat

Placebo

Drug

Placebo Gelatine capsule for oral administration. The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient (API).

Other names: Placebo Gelatine capsule

Primary outcomes

  1. Maximum observed plasma concentration (Cmax)

    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

    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

  2. Time to reach Cmax (Tmax)

    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

    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

  3. Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)

    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

    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

  4. Area under the plasma concentration-time curve from time 0 to the infinity (AUC0-∞)

    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

    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

  5. % of subjects with at least one adverse event

    Time frame: through study completion, an average of 72 hours

    Adverse events were continuously monitored from screening until the follow-up visit.

  6. % of subjects by dose group with at least one treatment-emergent adverse event (TEAEs)

    Time frame: through study completion, an average of 72 hours

    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.

  7. Apparent terminal elimination half-life (t1/2)

    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

    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

Sponsors and collaborators

Lead sponsor

Bial - Portela C S.A.

Industry

Registry information

Official study 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

Important dates

Study start
2007
Primary completion
2007
Study completion
2007
First posted
Jul 26, 2016
Registry last updated
Jul 26, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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