An Open-label Study in Healthy Male Subjects to Assess the Absorption, Distribution, Metabolism and Excretion of [14C]-Labelled BIA 9-1067 and Metabolites

Phase 1

Completed

Conditions: Parkinson's Disease (PD)

Interventions: Drug: OPC

Registration Number: NCT02169427

Lead Sponsor: Bial - Portela C S.A.

Brief Summary: The purpose of this study is to determine the rate and routes of excretion of OPC and the mass balance in urine, faeces and expired air.

Detailed Description: This was a single-centre, open-label ADME study in 6 healthy male subjects. Subjects received a single dose of 100 mg OPC, containing 3.39 MBq of \[14C\] OPC as oral capsules.

The study consisted of an eligibility screening period within 3 weeks prior to drug administration, admission on Day -1, a treatment period involving drug administration on Day 1 followed by matrix collections for PK purposes and safety evaluations up to Day 11, discharge on Day 11, six 24-hour hospitalizations on Days 14/15, 21/22 (+/ 1 day), 28/29 (+/- 1 day), 42/43 (+/- 2 days), 56/57 (+/- 2 days) and 77/78 (+/ 3 days) for PK sample collections, and a follow up visit performed at least 14 days after discharge from the last 24-hour hospitalization or at early discontinuation.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 6

Inclusion Criteria

Gender: male
Age: 18 - 55 years, inclusive
Body Mass Index (BMI): 18.0 - 30.0 kg/m2, inclusive Body weight (kg)and height2 (m2)
Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, "powerdrinks") and grapefruit (juice) from 48 hours prior to entry in the clinical research centre until discharge
Medical history without major pathology
Resting supine blood pressure and a resting pulse rate showing no clinically relevant deviations as judged by the MI
Computerised (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the MI
Willingness to use adequate contraception from the time of dosing until 3 months after the follow-up visit
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

Evidence of clinically relevant pathology
Mental handicap
History of relevant drug and/or food allergies
Regular/routine treatment with non-topical medications within 30 days prior to entrance into the clinical research centre
Smoking (less than 60 days prior to drug administration)
History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
Use of concomitant medication, except for acetaminophen (paracetamol), which was allowed up to 3 days before entrance into the clinical research centre. Multivitamins and vitamin C were allowed up to 7 days before entrance into the clinical research centre. All other medication (including over the counter medication, health supplements, and herbal remedies such as St. John's wort extract) was to be stopped at least 14 days prior to entrance into the clinical research centre
Participation in a drug study within 60 days prior to drug administration. Participation in more than 3 other drug studies in the 10 months preceding administration of study drug
Donation of more than 50 mL of blood within 60 days prior to drug administration. Donation of more than 1.5 litres of blood in the 10 months preceding administration of study drug
Participation in another ADME study with a radiation burden -0.1 mSv in the period of 1 year before the start of the study
Exposure to radiation for diagnostic reasons (except dental X-rays and plain X rays of thorax and bony skeleton - excluding spinal column), during work or during participation in a medical study in the previous year
Irregular defecation pattern (less than once per 2 days)
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
Illness within 5 days prior to drug administration

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Opicapone (OPC)	OPC	100 mg OPC

Primary Outcome Measures

Name	Time	Method
Cumulative Recovery of [14C]-Radioactivity	pre-dose and 0-6, 6-12, 12-24, 24-48, 48 72, 72-96, 96 120, 120-144, 144-168, 168-192, 192-216 and 216-240 hours post-dose; 24-hour collections on Days 14/15, 21/22, 28/29	AEurine: Cumulative Recovery of \[14C\]-Radioactivity in urine AEfaeces: Cumulative Recovery of \[14C\]-Radioactivity in urine AEair: Cumulative Recovery of \[14C\]-Radioactivity in urine AEtotal: Cumulative Recovery of \[14C\]-Radioactivity in urine Recovery % of dose has been derived from area under the excretion rate (to infinity) from 240h onwards

Secondary Outcome Measures

Name	Time	Method
Cmax - Maximum Concentration	pre-dose and 0-6, 6-12, 12-24, 24-48, 48 72, 72-96, 96 120, 120-144, 144-168, 168-192, 192-216 and 216-240 hours post-dose; 24-hour collections on Days 14/15, 21/22, 28/29	BIA 9-1103 is a Opicapone (OPC, BIA 9-1067) metabolite
Tmax - Time to Attain Maximum Concentration	pre-dose and 0-6, 6-12, 12-24, 24-48, 48 72, 72-96, 96 120, 120-144, 144-168, 168-192, 192-216 and 216-240 hours post-dose; 24-hour collections on Days 14/15, 21/22, 28/29	BIA 9-1103 is a Opicapone (OPC, BIA 9-1067) metabolite