Effect of BIA 9-1067 on Rasagiline Pharmacokinetics

• Sponsor: Bial - Portela C S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01532128
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 8
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect of BIA 9-1067 on rasagiline pharmacokinetics in healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: rasagiline; Drug: BIA 9-1067	Phase 1

Detailed Description

Single-centre, open-label, randomised, three-way crossover study consisting of 3 single-dose periods separated by a washout of 14 days or more

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of BIA 9-1067 on Rasagiline Pharmacokinetics in Healthy Subjects
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Period 1: rasagiline 1 mg Period 2: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 3: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg	Drug: rasagiline; 1 mg rasagiline (single-dose); Drug: BIA 9-1067; 50 mg BIA 9-1067 (single-dose)
Experimental: Group 2 Period 1: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 2: rasagiline 1 mg Period 3: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg	Drug: rasagiline; 1 mg rasagiline (single-dose); Drug: BIA 9-1067; 50 mg BIA 9-1067 (single-dose)
Experimental: Group 3 Period 1: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 2: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 3: rasagiline 1 mg	Drug: rasagiline; 1 mg rasagiline (single-dose); Drug: BIA 9-1067; 50 mg BIA 9-1067 (single-dose)

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Plasma Concentration [pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose]

Secondary Outcome Measures

1. Tmax - Time of Occurrence of Cmax [pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose]

2. AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration [pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects who were able and willing to give written informed consent.

• Male or female subjects aged between 18 and 45 years, inclusive.

• Subjects of body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive.

• Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.

• Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening

• Subjects who had clinical laboratory test results clinically acceptable at screening and admission to each treatment period.

• Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission to each treatment period.

• Subjects who were non-smokers or ex-smokers for at least 3 months.

• (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier or intrauterine device.

• (If female) She had a negative pregnancy test (β-HCG) at screening and 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.

• Subjects who had a clinically relevant surgical history.

• Subjects who had any significant abnormality in the coagulation tests.

• Subjects who had any significant abnormality in the liver function tests (a case-by-case decision for any abnormality was to be discussed with the Sponsor before inclusion).

• Subjects who had a history of relevant atopy or drug hypersensitivity.

• Subjects who had a history of alcoholism or drug abuse.

• Subjects who consumed more than 14 units of alcohol a week.

• Subjects who had a significant infection or known inflammatory process at screening or admission to each treatment period.

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

• Subjects who had received fluoxetine within 5 weeks of admission to the first period.

• Subjects who had used any other medicines within 2 weeks of admission to first period that could affected the safety or other study assessments, in the investigator's opinion.

• Subjects who had previously received BIA 9-1067.

• Subjects who have used any investigational drug or participated in any clinical trial within 90 days prior to screening.

• Subjects who have donated or received any blood or blood products within the 3 months prior to screening.

• Subjects who were vegetarians, vegans or have medical dietary restrictions.

• Subjects who could not communicated reliably with the investigator.

• Subjects who were unlikely to co-operate with the requirements of the study.

• Subjects who were unwilling or unable to give written informed consent.

• (If female) She was pregnant or breast-feeding.

• (If female) She was of childbearing potential and she did not use an approved effective contraceptive method (double-barrier, intra-uterine device) or she uses oral contraceptives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BIOTRIAL	Rennes		France	F-35000

Sponsors and Collaborators

• Bial - Portela C S.A.

Investigators

• Principal Investigator: Béatric Astruc, MD, Biotrial - Human Pharmacology Unit

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bial - Portela C S.A.
• ClinicalTrials.gov Identifier: NCT01532128
• Other Study ID Numbers: BIA-91067-112
• First Posted: Feb 14, 2012
• Last Update Posted: Aug 20, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Bial - Portela C S.A.: Parkinson Disease; BIA 9-1067
• Additional relevant MeSH terms: Parkinson Disease; Opicapone; Rasagiline

Study Results

Participant Flow

Arm/Group Title	Group 1	Group 2	Group 3
Arm/Group Description	Period 1: rasagiline 1 mg Period 2: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 3: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg rasagiline: 1 mg rasagiline (single-dose) BIA 9-1067: 50 mg BIA 9-1067 (single-dose)	Period 1: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 2: rasagiline 1 mg Period 3: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg rasagiline: 1 mg rasagiline (single-dose) BIA 9-1067: 50 mg BIA 9-1067 (single-dose)	Period 1: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 2: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 3: rasagiline 1 mg rasagiline: 1 mg rasagiline (single-dose) BIA 9-1067: 50 mg BIA 9-1067 (single-dose)
Period Title: Overall Study
STARTED	8	8	8
COMPLETED	8	8	8
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Group 3	Total
Arm/Group Description	Period 1: rasagiline 1 mg Period 2: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 3: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg rasagiline: 1 mg rasagiline (single-dose) BIA 9-1067: 50 mg BIA 9-1067 (single-dose)	Period 1: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 2: rasagiline 1 mg Period 3: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg rasagiline: 1 mg rasagiline (single-dose) BIA 9-1067: 50 mg BIA 9-1067 (single-dose)	Period 1: 50 mg BIA 9-1067. 1 hour later rasagiline 1 mg Period 2: rasagiline 1 mg concomitantly with BIA 9-1067 50 mg Period 3: rasagiline 1 mg rasagiline: 1 mg rasagiline (single-dose) BIA 9-1067: 50 mg BIA 9-1067 (single-dose)	Total of all reporting groups
Overall Participants	8	8	8	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	8 100%	24 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 50%	4 50%	4 50%	12 50%
Male	4 50%	4 50%	4 50%	12 50%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Plasma Concentration
Time Frame	pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline Alone	Rasagiline 1 h After BIA 9-1067	Rasagiline Concomitant BIA 9-1067
Arm/Group Description	Rasagiline alone.	Rasagiline 1 h after BIA 9-1067.	Rasagiline concomitant BIA 9-1067.
Measure Participants	24	24	24
BIA 9-1067	NA (NA)	672 (226)	643 (232)
Rasagiline	6152 (2245)	6.058 (2.399)	6.078 (2.255)

2. Secondary Outcome

Title	Tmax - Time of Occurrence of Cmax
Time Frame	pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline Alone	Rasagiline 1 h After BIA 9-1067	Rasagiline Concomitant BIA 9-1067
Arm/Group Description	Rasagiline alone.	Rasagiline 1 h after BIA 9-1067.	Rasagiline concomitant BIA 9-1067.
Measure Participants	24	24	24
BIA 9-1067	NA	2.00	2.50
Rasagiline	0.50	0.50	0.50

3. Secondary Outcome

Title	AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration
Time Frame	pre-dose, and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rasagiline Alone	Rasagiline 1 h After BIA 9-1067	Rasagiline Concomitant BIA 9-1067
Arm/Group Description	Rasagiline alone.	Rasagiline 1 h after BIA 9-1067.	Rasagiline concomitant BIA 9-1067.
Measure Participants	24	24	24
BIA 9-1067	NA (NA)	2133 (964.1)	1980 (861.1)
Rasagiline	4.323 (0.9727)	4.431 (1.010)	4.391 (0.8782)

Adverse Events

Arm/Group Title	Before Treatment		Rasagiline Alone		Rasagiline 1 h After BIA 9-1067		Rasagiline Concomitant BIA 9-1067
Arm/Group Description
All Cause Mortality
	Before Treatment		Rasagiline Alone		Rasagiline 1 h After BIA 9-1067		Rasagiline Concomitant BIA 9-1067
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Before Treatment		Rasagiline Alone		Rasagiline 1 h After BIA 9-1067		Rasagiline Concomitant BIA 9-1067
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Before Treatment		Rasagiline Alone		Rasagiline 1 h After BIA 9-1067		Rasagiline Concomitant BIA 9-1067
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/24 (4.2%)		6/24 (25%)		3/24 (12.5%)		3/24 (12.5%)
Gastrointestinal disorders
Diarrhoea	0/24 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
General disorders
Influenza like illness	0/24 (0%)		0/24 (0%)		0/24 (0%)		1/24 (4.2%)
Infections and infestations
Pharyngitis	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Investigations
Blood creatine phosphokinase increased	1/24 (4.2%)		3/24 (12.5%)		1/24 (4.2%)		0/24 (0%)
Nervous system disorders
Headache	0/24 (0%)		2/24 (8.3%)		1/24 (4.2%)		0/24 (0%)
Sciatica	0/24 (0%)		1/24 (4.2%)		1/24 (4.2%)		1/24 (4.2%)
Reproductive system and breast disorders
Dysmenorrhoea	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Erythema	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)
Pruritus	0/24 (0%)		1/24 (4.2%)		0/24 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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