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

A Double-blind, Randomised, Placebo-controlled Study to Evaluate the Tolerability, Pharmacokinetics and Pharmacodynamics of Six Multiple Rising Dose Regimens of BIA 5-453 in Healthy Male Volunteers

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

Study Overview

• Status: Completed
• Conditions: Hypertension; Chronic Heart Failure
• Intervention / Treatment: Drug: BIA 5-453; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIA 5-453 25 mg or placebo; Multiple oral doses of BIA 5-453 25 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.	Drug: BIA 5-453; Presented as blue hard gelatine capsules (size 2) of 1 mg, 10 mg and 50 mg for oral administration; Other Names: Etamicastat; Drug: Placebo; The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient.
Experimental: BIA 5-453 50 mg or placebo; Multiple oral doses of BIA 5-453 50 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.	Drug: BIA 5-453; Presented as blue hard gelatine capsules (size 2) of 1 mg, 10 mg and 50 mg for oral administration; Other Names: Etamicastat; Drug: Placebo; The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient.
Experimental: BIA 5-453 100 mg or placebo; Multiple oral doses of BIA 5-453 100 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.	Drug: BIA 5-453; Presented as blue hard gelatine capsules (size 2) of 1 mg, 10 mg and 50 mg for oral administration; Other Names: Etamicastat; Drug: Placebo; The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient.
Experimental: BIA 5-453 200 mg or placebo; Multiple oral doses of BIA 5-453 200 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.	Drug: BIA 5-453; Presented as blue hard gelatine capsules (size 2) of 1 mg, 10 mg and 50 mg for oral administration; Other Names: Etamicastat; Drug: Placebo; The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient.
Experimental: BIA 5-453 400 mg or placebo; Multiple oral doses of BIA 5-453 400 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.	Drug: BIA 5-453; Presented as blue hard gelatine capsules (size 2) of 1 mg, 10 mg and 50 mg for oral administration; Other Names: Etamicastat; Drug: Placebo; The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient.
Experimental: BIA 5-453 600 mg or placebo; Multiple oral doses of BIA 5-453 600 mg or placebo were administered once daily for 10 days to subjects in fasting conditions.	Drug: BIA 5-453; Presented as blue hard gelatine capsules (size 2) of 1 mg, 10 mg and 50 mg for oral administration; Other Names: Etamicastat; Drug: Placebo; The composition of the placebo is qualitatively the same but without BIA 5-453 pharmaceutical active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of subjects with at least one adverse event		through study completion, an average of 10 days
Percent of subjects by dose group with at least one treatment-emergent adverse event (TEAEs)	Treatment-emergent adverse events are adverse events that occurred either in the 72 hours after dosing or that was present prior to dosing but exacerbated within 72 hours after dosing.	through study completion, an average of 10 days

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimate): July 21, 2016

Study Record Updates

• Last Update Posted (Estimate): July 21, 2016
• Last Update Submitted That Met QC Criteria: July 20, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: BIA-5453-102; 2007-004142-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED