Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-BIA 9-1067
Primary Purpose
Parkinson Disease
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
[14C]-BIA 9-1067
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease
Eligibility Criteria
Inclusion Criteria:
- Healthy males;
- Age 30 to 65 years of age;
- Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator;
- Normal resting supine blood pressure and pulse or showing no clinically relevant deviation as judged by the investigator;
- Computerized (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator;
- 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;
- Must be willing and able to communicate and participate in the whole study;
- Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day);
- Must provide written informed consent;
- Must agree to use an adequate method of contraception
Exclusion Criteria:
- Females;
- Subjects who have received any IMP in a clinical research study within the previous 3 months;
- Subjects who are study site employees, or immediate family members of a study site or sponsor employee;
- Subjects who have previously been enrolled in this study;
- 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, 25 mL of 40% spirit or a 125 mL glass of wine);
- 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 1999, 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;
- Positive drugs of abuse test result;
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results;
- Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <90 mL/min using the Cockcroft-Gault equation;
- History of cardiovascular, neurological, renal, hepatic, chronic respiratory or gastrointestinal disease, or clinically significant psychiatric history as judged by the investigator;
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
- Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active;
- Donation or loss of greater than 400 mL of blood within the previous 3 months;
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 2 g per day paracetamol) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor;
- Failure to satisfy the investigator of fitness to participate for any other reason.
Sites / Locations
- Quotient Clinical
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Reguimen A - [14C]-BIA 9-1067
Arm Description
100 mg [14C]-BIA 9-1067 Capsule containing not more than 3.3 MBq (89.2 µCi) 14C; will be administered with 240 mL water. Single dose administration on a single occasion.
Outcomes
Primary Outcome Measures
Mass balance recovery of total radioactivity in all (urine, faeces and expired air combined) amount excreted (Ae) expressed as a percentage of the administered dose (%Ae)
Mass balance of total radioactivity in urine, faeces and expired air
Mass balance recovery of total radioactivity in all (urine, faeces and expired air combined) cumulative recovery (CumAe) expressed as a percentage of the administered dose (Cum%Ae)
Mass balance of total radioactivity in urine, faeces and expired air
Secondary Outcome Measures
Tlag: the elapsed time from dosing at which analyte was first quantifiable in a concentration vs time profile
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Cmax: maximum observed concentration
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Tmax: the time from dosing at which Cmax was apparent
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
AUC0-t: area under the curve from 0 time to last measurable concentration
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03119194
Brief Title
Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-BIA 9-1067
Official Title
An Open-Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-BIA 9-1067 in Healthy Male Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
January 27, 2017 (Actual)
Primary Completion Date
April 27, 2017 (Actual)
Study Completion Date
April 27, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bial - Portela C S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose is to and to assess the mass balance recovery after a single oral dose of [14C]-BIA 9-1067 and to provide plasma, urine and faecal samples for metabolite profiling and structural identification.
Detailed Description
This is an open-label, single-dose, single-period, non-randomised study in healthy male subjects. Subjects will be screened for eligibility to participate in the study between 28 and 2 days before dosing. Eligible subjects will be admitted to the clinical unit on the evening of the day before dosing (Day -1). Subjects will be dosed on the morning of Day 1 following an overnight fast of approximately 8 h. Blood, urine, faeces and expired air will be collected at predefined time points for mass balance and PK analysis. Subjects will remain resident in the clinic until the morning of Day 22, when they will be discharged as a group.
Single dose administration on a single occasion. The estimated duration of the study from screening until the final return visit is approximately 3.5 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reguimen A - [14C]-BIA 9-1067
Arm Type
Experimental
Arm Description
100 mg [14C]-BIA 9-1067 Capsule containing not more than 3.3 MBq (89.2 µCi) 14C; will be administered with 240 mL water.
Single dose administration on a single occasion.
Intervention Type
Drug
Intervention Name(s)
[14C]-BIA 9-1067
Intervention Description
1 × 100 mg capsule, Oral
Primary Outcome Measure Information:
Title
Mass balance recovery of total radioactivity in all (urine, faeces and expired air combined) amount excreted (Ae) expressed as a percentage of the administered dose (%Ae)
Description
Mass balance of total radioactivity in urine, faeces and expired air
Time Frame
Urine and faeces: pre-dose,0,0.25,0.5,0.75,1,1.5, 2, 3, 4, 6,8,12,18,24,36,48,72,96,120,144,168,240,312,408,504,648 hours after dosing. Expired air: Pre-dose, 0.5,1,1.5,2,4,6,8,12,18,24,36,48,72,96,120,168,240,312,408,504 hours after dosing.
Title
Mass balance recovery of total radioactivity in all (urine, faeces and expired air combined) cumulative recovery (CumAe) expressed as a percentage of the administered dose (Cum%Ae)
Description
Mass balance of total radioactivity in urine, faeces and expired air
Time Frame
Urine and faeces: pre-dose,0,0.25,0.5,0.75,1,1.5, 2, 3, 4, 6,8,12,18,24,36,48,72,96,120,144,168,240,312,408,504,648 hours after dosing. Expired air: Pre-dose, 0.5,1,1.5,2,4,6,8,12,18,24,36,48,72,96,120,168,240,312,408,504 hours after dosing.
Secondary Outcome Measure Information:
Title
Tlag: the elapsed time from dosing at which analyte was first quantifiable in a concentration vs time profile
Description
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Time Frame
Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 240, 408, 504 hours after dosing
Title
Cmax: maximum observed concentration
Description
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Time Frame
Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 240, 408, 504 hours after dosing
Title
Tmax: the time from dosing at which Cmax was apparent
Description
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Time Frame
Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 240, 408, 504 hours after dosing
Title
AUC0-t: area under the curve from 0 time to last measurable concentration
Description
Pharmacokinetic Data Analysis for BIA 9-1067 and its metabolites, BIA 9-1103 and BIA 9-4588
Time Frame
Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 240, 408, 504 hours after dosing
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy males;
Age 30 to 65 years of age;
Body mass index of 18.0 to 35.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator;
Normal resting supine blood pressure and pulse or showing no clinically relevant deviation as judged by the investigator;
Computerized (12-lead) ECG recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the investigator;
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;
Must be willing and able to communicate and participate in the whole study;
Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day);
Must provide written informed consent;
Must agree to use an adequate method of contraception
Exclusion Criteria:
Females;
Subjects who have received any IMP in a clinical research study within the previous 3 months;
Subjects who are study site employees, or immediate family members of a study site or sponsor employee;
Subjects who have previously been enrolled in this study;
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, 25 mL of 40% spirit or a 125 mL glass of wine);
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 1999, 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;
Positive drugs of abuse test result;
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results;
Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <90 mL/min using the Cockcroft-Gault equation;
History of cardiovascular, neurological, renal, hepatic, chronic respiratory or gastrointestinal disease, or clinically significant psychiatric history as judged by the investigator;
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active;
Donation or loss of greater than 400 mL of blood within the previous 3 months;
Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 2 g per day paracetamol) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor;
Failure to satisfy the investigator of fitness to participate for any other reason.
Facility Information:
Facility Name
Quotient Clinical
City
Ruddington
State/Province
Nottingham
ZIP/Postal Code
NG11 6JS
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-BIA 9-1067
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