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

• Sponsor: Bial - Portela C S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02169427
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 4
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease (PD)	Drug: OPC	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study in Healthy Male Subjects to Assess the Absorption, Distribution, Metabolism and Excretion of [14C]-Labelled BIA 9-1067 and Metabolites Following a Single Dose Oral Administration
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Opicapone (OPC) 100 mg OPC	Drug: OPC; The drug substance of 100 mg OPC was administered as 1 capsule.; Other Names: BIA 9-1067

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Gender: male

2. Age: 18 - 55 years, inclusive

3. Body Mass Index (BMI): 18.0 - 30.0 kg/m2, inclusive Body weight (kg)and height2 (m2)

4. 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

5. Medical history without major pathology

6. Resting supine blood pressure and a resting pulse rate showing no clinically relevant deviations as judged by the MI

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

8. Willingness to use adequate contraception from the time of dosing until 3 months after the follow-up visit

9. 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

10. Willingness to sign the written ICF

Exclusion Criteria:

1. Evidence of clinically relevant pathology

2. Mental handicap

3. History of relevant drug and/or food allergies

4. Regular/routine treatment with non-topical medications within 30 days prior to entrance into the clinical research centre

5. Smoking (less than 60 days prior to drug administration)

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

7. 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

8. 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

9. 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

10. Participation in another ADME study with a radiation burden -0.1 mSv in the period of 1 year before the start of the study

11. 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

12. Irregular defecation pattern (less than once per 2 days)

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

14. 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)

15. Positive screen on hepatitis B surface antigen (HBsAg)

16. Positive screen on anti-hepatitis C virus (HCV)

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

18. Illness within 5 days prior to drug administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA	Zuidlaren		Netherlands	9471 GP

Sponsors and Collaborators

• Bial - Portela C S.A.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT02169427
• Other Study ID Numbers: BIA-91067-122
• First Posted: Jun 23, 2014
• Last Update Posted: Aug 21, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Bial - Portela C S.A.: Parkinson's disease (PD); BIA 9-1067; Opicapone
• Additional relevant MeSH terms: Parkinson Disease; Opicapone

Study Results

Participant Flow

Arm/Group Title	Opicapone (OPC)
Arm/Group Description	100 mg OPC OPC: The drug substance of 100 mg OPC was administered as 1 capsule.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Opicapone (OPC)
Arm/Group Description	100 mg OPC OPC: The drug substance of 100 mg OPC was administered as 1 capsule.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%

Outcome Measures

1. Primary Outcome

Title	Cumulative Recovery of [14C]-Radioactivity
Description	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
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Opicapone (OPC)
Arm/Group Description	100 mg OPC OPC: The drug substance of 100 mg OPC was administered as 1 capsule.
Measure Participants	6
AEurine	12.8 (1.5)
AEfaeces	67.2 (7.6)
AEair	15.9 (4.8)
AEtotal	95.9 (8.6)

2. Secondary Outcome

Title	Cmax - Maximum Concentration
Description	BIA 9-1103 is a Opicapone (OPC, BIA 9-1067) metabolite
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Opicapone (OPC)
Arm/Group Description	100 mg OPC OPC: The drug substance of 100 mg OPC was administered as 1 capsule.
Measure Participants	6
14C plasma	7302 (3918)
14C blood	1920 (813)
OPC plasma	757 (321)
BIA 9-1103 plasma	118 (60.9)

3. Secondary Outcome

Title	Tmax - Time to Attain Maximum Concentration
Description	BIA 9-1103 is a Opicapone (OPC, BIA 9-1067) metabolite
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Opicapone (OPC)
Arm/Group Description	100 mg OPC OPC: The drug substance of 100 mg OPC was administered as 1 capsule.
Measure Participants	6
14C plasma	0.51 (0.01)
14C blood	1.01 (0.01)
OPC plasma	2.43 (1.10)
BIA 9-1103 plasma	8.34 (3.88)

Adverse Events

Arm/Group Title	Opicapone (OPC)
Arm/Group Description	100 mg OPC OPC: The drug substance of 100 mg OPC was administered as 1 capsule.
All Cause Mortality
	Opicapone (OPC)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Opicapone (OPC)
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Opicapone (OPC)
	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)
Gastrointestinal disorders
Frequent Bowel Movements	1/6 (16.7%)
Injury, poisoning and procedural complications
Wound	1/6 (16.7%)
Nervous system disorders
Headache	1/6 (16.7%)
Somnolence	2/6 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.