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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02151994
Other study ID # BIA-51058-101
Secondary ID
Status Completed
Phase Phase 1
First received May 26, 2014
Last updated November 26, 2015
Start date March 2011
Est. completion date January 2012

Study information

Verified date November 2015
Source Bial - Portela C S.A.
Contact n/a
Is FDA regulated No
Health authority Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study type Interventional

Clinical Trial Summary

The purpose of this study is to to assess the safety and tolerability of BIA 5 1058 after single and multiple oral doses


Description:

This was a Phase 1, double blind, randomised, placebo-controlled combined single ascending dose (SAD), including food interaction (food effect, FE) analysis, and multiple ascending dose (MAD) study.

SAD: This part consisted of an eligibility screening period, one study period involving administration of single doses of BIA 5-1058 or placebo according to a randomized design, and a follow-up period. Nine sequential groups of 8 healthy young male subjects were dosed. Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo. In this first-in-human study, the subjects participating at the lowest dose level of 5 mg were dosed according to a sentinel dosing design to ensure optimal safety. Initially, 2 subjects were dosed; 1 subject with BIA 5-1058 and 1 subject with placebo. After the safety and tolerability results of the first 24 h following dosing for the initial subjects had been found to be acceptable to the MI, the other 6 subjects of the lowest dose level were dosed.

MAD: This part consisted of an eligibility screening period, one study period involving administration of multiple doses of BIA 5-1058 or placebo once daily for 10 days, and a follow-up period. Five sequential groups of 8 healthy young male subjects were dosed.

Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo.

The starting dose of 50 mg was chosen taking into consideration the dose range of the previous SAD sequential groups and was approved by the IEC. Escalation to the next higher dose and the determination of the next dose level was based on safety, tolerability and available PK results of the previously administered dose

FE: This part consisted of an eligibility screening period, an open-label two-way crossover study period, and a follow-up period. One group of 12 subjects received single doses of 400 mg BIA 5-1058 during 2 treatment periods, once after having fasted overnight and once after consumption of a high fat breakfast. Each treatment was separated by a period of at least 7 days. The treatment sequence was determined by randomisation.


Recruitment information / eligibility

Status Completed
Enrollment 124
Est. completion date January 2012
Est. primary completion date January 2012
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria:

Subjects were eligible for the study if they met all the following inclusion criteria:

- Gender - male

- Age - 18 - 55 years, inclusive

- Body Mass Index (BMI) - 18.0 - 30.0 kg m2 (BMI (kg m2) = Body weight (kg) - Heigh t2 (m 2))

- Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, power drinks), grapefruit (juice) and tobacco products from 48 h prior to entry in the clinical research centre until discharge

- Medical history without major pathology

- Normal resting supine blood pressure and pulse rate showing no clinically relevant deviations as judged by the MI

- Computerised (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the MI

- All values for haematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the MI

- Willingness to sign the written ICF

Exclusion Criteria:

Subjects were excluded from participation if any of the following exclusion criteria applied

- Any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, haematological, neurologic, or psychiatric disease

- An automatic ECG QTc interval reading at screening or enrolment of + 440 ms.

- Evidence of clinically relevant pathology

- Mental handicap

- History of relevant drug and or food allergies

- Smoking more than 10 cigarettes and or cigars and or pipes daily

- History of alcohol abuse or drug addiction (including soft drugs like cannabis products)

- Use of any prescription drug within 30 days before study drug administration with the exception of influenza vaccination

- Use of any over-the-counter drugs including health supplements, herbal supplements such as St. John's Wort extract (except for the occasional use of acetaminophen (paracetamol), aspirin and vitamins - 100 recommended daily allowance) within 7 days before study drug administration. The use of paracetamol and or topical medication was allowed up to 3 days before entrance into the clinical research facility

- Participation in a drug study within 90 days prior to drug administration

- Participation in more than 3 other drug studies in the 10 months preceding the start of this study (this was the first administration of study drug)

- Donation of more than 50 mL of blood within 90 days prior to first drug administration

- Donation of more than 1.5 litres of blood in the 10 months preceding the start of this study (this was the first administration of study drug)

- Positive screen on drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids), barbiturates, benzodiazepines, tricyclic antidepressants and alcohol

- Intake of more than 24 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)

- Positive screen on hepatitis B surface antigen (HBsAg)

- Positive screen on anti hepatitis C virus (HCV)

- Positive screen on anti human immunodeficiency virus (HIV) 1 - 2

- Acute disease state indicated as clinically relevant by the MI (e.g. nausea, vomiting, fever, diarrhoea) within 7 days before the first drug administration

- Non-willingness to consume the Food and Drug Administration (FDA) breakfast (FE part only)

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
BIA 5-1058
oral administration
Placebo
oral administration

Locations

Country Name City State
Netherlands PRA Zuidlaren

Sponsors (1)

Lead Sponsor Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Single Ascending Dose (SAD) Period Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite". Just before drug administration and twice daily until 72 h after (last) drug administration Yes
Primary Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Multiple Ascending Dose (MAD) Period Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite". Just before drug administration and twice daily until 72 h after (last) drug administration Yes
Primary Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Food Effect (FE) Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite". Just before drug administration and twice daily until 72 h after (last) drug administration Yes