Relative Bioavailability and Bioequivalence Of Different Formulations of Opicapone in Healthy Volunteers

• Sponsor: Bial - Portela C S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02305277
• Collaborator: (none)
• Enrollment: 85
• Arms: 6
• Duration (Months): 3

Study Details

Study Description

Brief Summary

Single-centre, open-label, randomised, three-part, two-way crossover study in 84 healthy volunteers. In each part, the study consisted of two consecutive single-dose treatment periods separated by a washout period of at least 14 days.

Condition or Disease	Intervention/Treatment	Phase
Parkinson	Drug: BIA 9-1067 (clinical micronized, CM); Drug: BIA 9-1067 (to-be-marketed, TBM)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relative Bioavailability and Bioequivalence Of Different Formulations of Opicapone in Healthy Volunteers
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BIA 9-1067 5 mg Sequence 1 volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone ; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 25 mg Sequence 1 volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone ; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 50 mg Sequence 1 volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone ; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 5 mg Sequence 2 volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone ; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 25 mg Sequence 2 volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone ; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone
Experimental: BIA 9-1067 50 mg Sequence 2 volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed	Drug: BIA 9-1067 (clinical micronized, CM); Other Names: OPC, Opicapone ; Drug: BIA 9-1067 (to-be-marketed, TBM); Other Names: OPC, Opicapone

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Plasma Concentration [before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose]

Secondary Outcome Measures

1. AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067 [before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose]

   Area Under the plasma concentration-time Curve from time 0 to the time of last quantifiable concentration

2. Tmax - Time of Occurrence of Cmax [before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A signed and dated informed consent form before any study-specific screening procedure was performed;

• Male or female subjects aged 18 to 45 years, inclusive;

• Body mass index (BMI) between 18 and 30 kg/m2 inclusive;

• Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead electrocardiogram (ECG);

• Negative tests for hepatitis B surface antigen (HBsAg), anti- hepatitis C virus antibodies (HCV Ab) and anti-human immunodeficiency virus antibodies (HIV-1 and HIV-2 Ab) at screening;

• Clinical laboratory test results clinically acceptable at screening and admission to each treatment period;

• Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period;

• Non-smokers or ex-smokers for at least 3 months;

• Able to participate, and willing to give written informed consent and comply with the study restrictions.

• If female:

• She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used an effective non-hormonal method of contraception [intrauterine device or intrauterine system; condom or occlusive cap (diaphragm or cervical or vault caps) with spermicidal foam or gel or film or cream or suppository; true abstinence; or vasectomized male partner, provided that he was the sole partner of that subject] for all the duration of the study;

• She had a negative serum pregnancy test at screening and a negative urine pregnancy test at admission to each treatment period.

Exclusion Criteria:

• Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders, or had a clinically relevant surgical history;

• Had clinically relevant findings in laboratory tests, particularly any abnormality in the coagulation tests, or any abnormality in the liver function tests;

• Had a history of relevant atopy or drug hypersensitivity;

• Had a history of alcoholism and/or drug abuse;

• Consumed more than 14 units of alcohol per week [1 unit of alcohol = 280 mL beer (3-4°) = 100 mL wine (10-12°) = 30 mL spirits (40°)];

• Had a significant infection or known inflammatory process on screening or admission to each treatment period;

• Had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period;

• Had used medicines within 2 weeks of admission to first period that could affect the safety or other study assessments, in the Investigator's opinion;

• Had previously received opicapone;

• Had used any investigational drug or participated in any clinical trial within 90 days prior to screening;

• Had participated in more than 2 clinical trials within the 12 months prior to screening;

• Had donated or received any blood or blood products within the 3 months prior to screening;

• Were vegetarians, vegans or had medical dietary restrictions;

• Could not communicate reliably with the Investigator;

• Were unlikely to co-operate with the requirements of the study;

• Were unwilling or unable to give written informed consent;

If female:

• She was pregnant or breast-feeding.

Contacts and Locations

Locations

No locations specified.

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: NCT02305277
• Other Study ID Numbers: BIA-91067-119
• First Posted: Dec 2, 2014
• Last Update Posted: Nov 17, 2015
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Opicapone

Study Results

Participant Flow

Arm/Group Title	BIA 9-1067 5 mg Sequence 1	BIA 9-1067 25 mg Sequence 1	BIA 9-1067 50 mg Sequence 1	BIA 9-1067 5 mg Sequence 2	BIA 9-1067 25 mg Sequence 2	BIA 9-1067 50 mg Sequence 2
Arm/Group Description	volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)
Period Title: Overall Study
STARTED	15	14	14	14	14	14
Received CM	15	14	14	14	14	14
Received TBM	15	14	14	14	14	14
COMPLETED	14	14	14	14	13	14
NOT COMPLETED	1	0	0	0	1	0

Baseline Characteristics

Arm/Group Title	BIA 9-1067 5 mg Sequence 1	BIA 9-1067 25 mg Sequence 1	BIA 9-1067 50 mg Sequence 1	BIA 9-1067 5 mg Sequence 2	BIA 9-1067 25 mg Sequence 2	BIA 9-1067 50 mg Sequence 2	Total
Arm/Group Description	volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: CM Formulation Period 2: TBM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 5 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 25 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	volunteers received a single oral dose of 50 mg BIA 9-1067: Period 1: TBM Formulation Period 2: CM Formulation CM - clinical micronized TBM - to-be-marketed BIA 9-1067 (clinical micronized, CM) BIA 9-1067 (to-be-marketed, TBM)	Total of all reporting groups
Overall Participants	15	14	14	14	14	14	85
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	14 100%	14 100%	14 100%	14 100%	14 100%	85 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 46.7%	6 42.9%	6 42.9%	6 42.9%	6 42.9%	6 42.9%	37 43.5%
Male	8 53.3%	8 57.1%	8 57.1%	8 57.1%	8 57.1%	8 57.1%	48 56.5%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Plasma Concentration
Time Frame	before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BIA 9-1067 5 mg CM	BIA 9-1067 5 mg TBM	BIA 9-1067 25 mg CM	BIA 9-1067 25 mg TBM	BIA 9-1067 50 mg CM	BIA 9-1067 50 mg TBM
Arm/Group Description	BIA 9-1067 5 mg CM CM - clinical micronized	BIA 9-1067 5 mg TBM TBM - to-be-marketed	BIA 9-1067 25 mg CM CM - clinical micronized	BIA 9-1067 25 mg TBM TBM - to-be-marketed	BIA 9-1067 50 mg CM CM - clinical micronized	BIA 9-1067 50 mg TBM TBM - to-be-marketed
Measure Participants	29	28	28	28	28	28
Mean (Standard Deviation) [ng/mL]	107.3 (55.7)	95.5 (37.8)	424.5 (155.7)	471.0 (206.9)	756.2 (302.4)	802.9 (363.0)

2. Secondary Outcome

Title	AUC0-t - Area Under the Plasma Concentration-time Curve for BIA 9-1067
Description	Area Under the plasma concentration-time Curve from time 0 to the time of last quantifiable concentration
Time Frame	before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BIA 9-1067 5 mg CM	BIA 9-1067 5 mg TBM	BIA 9-1067 25 mg CM	BIA 9-1067 25 mg TBM	BIA 9-1067 50 mg CM	BIA 9-1067 50 mg TBM
Arm/Group Description	BIA 9-1067 5 mg CM CM - clinical micronized	BIA 9-1067 5 mg TBM TBM - to-be-marketed	BIA 9-1067 25 mg CM CM - clinical micronized	BIA 9-1067 25 mg TBM TBM - to-be-marketed	BIA 9-1067 50 mg CM CM - clinical micronized	BIA 9-1067 50 mg TBM TBM - to-be-marketed
Measure Participants	29	28	28	28	28	28
Mean (Standard Deviation) [ng.h/mL]	196.8 (128.5)	197.7 (89.7)	1137 (413.8)	1270 (515.5)	2043 (1032)	2161 (1110)

3. Secondary Outcome

Title	Tmax - Time of Occurrence of Cmax
Time Frame	before OPC dosing, and ½, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-OPC dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BIA 9-1067 5 mg CM	BIA 9-1067 5 mg TBM	BIA 9-1067 25 mg CM	BIA 9-1067 25 mg TBM	BIA 9-1067 50 mg CM	BIA 9-1067 50 mg TBM
Arm/Group Description	BIA 9-1067 5 mg CM CM - clinical micronized	BIA 9-1067 5 mg TBM TBM - to-be-marketed	BIA 9-1067 25 mg CM CM - clinical micronized	BIA 9-1067 25 mg TBM TBM - to-be-marketed	BIA 9-1067 50 mg CM CM - clinical micronized	BIA 9-1067 50 mg TBM TBM - to-be-marketed
Measure Participants	29	28	28	28	28	28
Median (Full Range) [hours]	2.00	1.00	2.00	2.00	2.00	2.00

Adverse Events

Arm/Group Title	BIA 9-1067 5 mg CM		BIA 9-1067 5 mg TBM		BIA 9-1067 25 mg CM		BIA 9-1067 25 mg TBM		BIA 9-1067 50 mg CM		BIA 9-1067 50 mg TBM
Arm/Group Description	BIA 9-1067 5 mg CM CM - clinical micronized		BIA 9-1067 5 mg TBM TBM - to-be-marketed		BIA 9-1067 25 mg CM CM - clinical micronized		BIA 9-1067 25 mg TBM TBM - to-be-marketed		BIA 9-1067 50 mg CM CM - clinical micronized		BIA 9-1067 50 mg TBM TBM - to-be-marketed
All Cause Mortality
	BIA 9-1067 5 mg CM		BIA 9-1067 5 mg TBM		BIA 9-1067 25 mg CM		BIA 9-1067 25 mg TBM		BIA 9-1067 50 mg CM		BIA 9-1067 50 mg TBM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BIA 9-1067 5 mg CM		BIA 9-1067 5 mg TBM		BIA 9-1067 25 mg CM		BIA 9-1067 25 mg TBM		BIA 9-1067 50 mg CM		BIA 9-1067 50 mg TBM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Injury, poisoning and procedural complications
Joint dislocation	0/29 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	BIA 9-1067 5 mg CM		BIA 9-1067 5 mg TBM		BIA 9-1067 25 mg CM		BIA 9-1067 25 mg TBM		BIA 9-1067 50 mg CM		BIA 9-1067 50 mg TBM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		3/28 (10.7%)		6/28 (21.4%)		3/28 (10.7%)		1/28 (3.6%)		3/28 (10.7%)
Gastrointestinal disorders
Nausea	0/29 (0%)		1/28 (3.6%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)
Abdominal pain	0/29 (0%)		0/28 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)
Diarrhoea	0/29 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Infections and infestations
Conjunctivitis	0/29 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Nasopharyngitis	0/29 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Injury, poisoning and procedural complications
Joint dislocation	0/29 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/29 (0%)		0/28 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)		1/28 (3.6%)
Nervous system disorders
Headache	1/29 (3.4%)		2/28 (7.1%)		2/28 (7.1%)		1/28 (3.6%)		0/28 (0%)		2/28 (7.1%)
Dizziness postural	0/29 (0%)		0/28 (0%)		0/28 (0%)		2/28 (7.1%)		0/28 (0%)		1/28 (3.6%)
Reproductive system and breast disorders
Metrorrhagia	0/29 (0%)		0/28 (0%)		0/28 (0%)		0/28 (0%)		1/28 (3.6%)		0/28 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/29 (0%)		0/28 (0%)		2/28 (7.1%)		0/28 (0%)		0/28 (0%)		0/28 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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