Tolerability, Pharmacokinetics and Pharmacodynamics of Six Multiple Rising Dose Regimens of BIA 5-453

BIAL

Status and phase: Completed; Phase 1

Conditions: Hypertension; Chronic Heart Failure

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02840565

BIA-5453-102

2007-004142-33 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to assess the tolerability of BIA 5-453 after six multiple rising dose regimens of BIA 5-453.

Full description

Two centres, double-blind, randomised, placebo-controlled study of six dosage regimens of BIA 5-453 in six groups of healthy male subjects.

In each group, the study consisted of a 10-day multiple-dose period. Progression to the next dose level only occurred if the previous dose level was considered to be safe and well tolerated. An appropriate interval separated the investigation of doses to permit a timely review and evaluation of safety data (including plasma exploratory pharmacokinetics) prior to proceeding to a higher dose level.

Enrollment: 57 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 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 Day1.

3. History of drug abuse within 1 year before study Day1.

4. History of alcoholism within 1 year before Day1. 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 Day1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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57 participants in 6 patient groups

BIA 5-453 25 mg or placebo

Experimental group

Description:

Multiple oral doses of BIA 5-453 25 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.

Treatment:

Drug: Placebo

Drug: BIA 5-453

BIA 5-453 50 mg or placebo

Experimental group

Description:

Multiple oral doses of BIA 5-453 50 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.

Treatment:

Drug: Placebo

Drug: BIA 5-453

BIA 5-453 100 mg or placebo

Experimental group

Description:

Multiple oral doses of BIA 5-453 100 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.

Treatment:

Drug: Placebo

Drug: BIA 5-453

BIA 5-453 200 mg or placebo

Experimental group

Description:

Multiple oral doses of BIA 5-453 200 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.

Treatment:

Drug: Placebo

Drug: BIA 5-453

BIA 5-453 400 mg or placebo

Experimental group

Description:

Multiple oral doses of BIA 5-453 400 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.

Treatment:

Drug: Placebo

Drug: BIA 5-453

BIA 5-453 600 mg or placebo

Experimental group

Description:

Multiple oral doses of BIA 5-453 600 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.

Treatment:

Drug: Placebo

Drug: BIA 5-453