Clinical trial NCT02845037: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Chronic Heart Failure
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2016-07-26
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: 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
measure: Time to reach Cmax (Tmax)
timeFrame: 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
measure: Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t)
timeFrame: 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
measure: Area under the plasma concentration-time curve from time 0 to the infinity (AUC0-∞)
timeFrame: 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
measure: % of subjects with at least one adverse event
timeFrame: through study completion, an average of 72 hours
measure: % of subjects by dose group with at least one treatment-emergent adverse event (TEAEs)
timeFrame: through study completion, an average of 72 hours
measure: Apparent terminal elimination half-life (t1/2)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Rennes
country: France
facility: Biotrial
Study officials:
References: