Absorption, Distribution, Metabolism and Excretion of [14C] Labelled BIA 5-1058

NCT04069130 | Completed Phase 1

• 1 other identifier: BIA-51058-119
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the mass balance recovery in expired air, urine and faeces after a single oral dose of 400 mg 14C-labeled BIA 5-1058; to provide plasma, urine and faecal samples for metabolite profiling and structural identification; and determine the routes and rates of elimination of \[14C\]-BIA 5-1058

Conditions

Cardiovascular Diseases

Outcome Measures

Primary Outcomes (27)

• Ae(urine) - amount excreted in urine

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Ae(faeces) - amount excreted in faeces

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Ae(expired air) - amount excreted in expired air

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Ae(total) - amount excreted in urine, faeces and expired air combined

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• CumAe(urine) - cumulative amount excreted in urine

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• CumAe(faeces) - cumulative amount excreted in faeces

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• CumAe(expired air) - cumulative amount excreted in expired air

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• CumAe(total) - cumulative amount excreted in urine, faeces and expired air combined

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• %Ae(urine) - amount excreted in urine expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• %Ae(faeces) - amount excreted in faeces expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• %Ae(expired air) - amount excreted in expired air expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• %Ae(total) - amount excreted in urine, faeces and expired air combined expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Cum%Ae(urine) - cumulative amount excreted in urine expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Cum%Ae(faeces) - cumulative amount excreted in faeces expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Cum %Ae(expired air) - cumulative amount excreted in expired air expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Cum %Ae(total) - cumulative amount excreted in urine, faeces and expired air combined expressed as a percentage of the administered dose

  Calculation of Mass balance of total radioactivity

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Tmax- the time from dosing at which Cmax was apparent

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Cmax - maximum observed concentration

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• C24 - plasma concentration at 24 h

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• AUC(0-last) - area under the curve from 0 time to last measurable concentration

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• AUC(0-inf) - area under the curve from 0 time extrapolated to infinity

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• AUC%extrap - percentage of AUC(0-inf) extrapolated beyond last measured time point

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Lambda-z - the slope of the apparent elimination phase

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Kel - elimination rate constant

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• T1/2 - the apparent elimination half-life

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• CL/F - total body clearance after extravascular administration (for BIA 5 1058 in plasma only)

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

• Vz/F - apparent volume of distribution based on the terminal phase after extravascular administration (for BIA 5 1058 in plasma only).

  Pharmacokinetic Data Analysis

  Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15.

Study Arms (1)

BIA 5

EXPERIMENTAL

single oral dose of 400 mg as an oral capsule

Drug: 400 mg of BIA 5-1058

Interventions

400 mg of BIA 5-1058 DRUG

1 x 400 mg capsule Oral, Fasted

BIA 5

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males;
• Age 30 to 65 years of age, inclusive;
• Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive;
• Normal resting supine BP (Systolic BP: 90-140 mmHg \[age 18-45\] 90 160 mmHg \[age \>45\], Diastolic BP: 40-90 mmHg) and heart rate: 40-90 bpm (age 18-45) 50-90 bpm (age \>45) or showing no clinically relevant deviation as judged by the investigator or delegate;
• Digital (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator or delegate;
• All values for clinical laboratory tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the investigator or delegate;
• Must be willing and able to communicate and participate in the whole study;
• Must have regular bowel movements (ie, average stool production of between ≥1 every 2 days and ≤3 stools per day);
• Must provide written informed consent;
• Must agree to adhere to the contraception requirements

You may not qualify if:

• Females;
• Subjects who have received any IMP in a clinical research study within the previous 90 days prior to Day 1 of the study;
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee;
• Subjects who have previously received BIA 5-1058 (including participation in QCL118167);
• History of any drug or alcohol abuse in the past 2 years;
• Regular alcohol consumption in males \>21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type);
• Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening and admission;
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months;
• Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study;
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening;
• Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 2);
• Positive drugs of abuse test result;
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results;
• An estimated creatinine clearance of \<90 mL/min based on creatinine clearance calculation using the Cockcroft-Gault equation and normalised to an average surface area of 1.73 m2;
• Clinically significant history of cardiovascular, renal, hepatic, respiratory and particularly GI disease, especially peptic ulceration, GI bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome, as judged by the investigator or sub investigator;

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 28, 2019
• Study Start: January 22, 2019
• Primary Completion: May 2, 2019
• Study Completion: May 2, 2019
• Last Updated: December 31, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)