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

BIAL

Status and phase: Completed; Phase 1

Conditions: Hypertension; Chronic Heart Failure

Treatments: Drug: Placebo; Drug: BIA 5-453

Study type: Interventional

Funder types: Industry

Identifiers

NCT02845037

BIA-5453-101

Details and patient eligibility

About

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

Full 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.

Enrollment: 80 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. A signed and dated informed consent form before any study-specific screening procedure was performed.
2. Aged between 18 and 45 years, inclusive.
3. 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).
4. 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.
5. Have a high probability for compliance with and completion of the study.

Exclusion criteria

Medical History

1. 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.

2. Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study day 1.

3. History of drug abuse within 1 year before study day 1.

4. 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

5. History of any clinically important drug allergy.

   Physical and Laboratory Findings

6. An automatic ECG QTc interval reading at screening or enrolment >450 ms.

7. Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.

8. Positive findings of urine drug screen (eg, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).

   Prohibited treatments

9. Prohibited Treatments: use of any investigational drug within 90 days or prescription drug within 30 days before investigational medical product (IMP) administration.

10. 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.

11. 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.

12. Donation of blood (ie 450 ml) within 90 days before study day 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 10 patient groups

2 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

10 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

20 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

50 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

100 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

200 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

400 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

600 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

900 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo

1200 mg or placebo

Experimental group

Description:

BIA 5-453 or placebo

Treatment:

Drug: BIA 5-453

Drug: Placebo