- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01879748
A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Rasagiline
A Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses (0.5, 1.0, and 2.0 mg) of Rasagiline Administered to Healthy Japanese and Caucasian Subjects
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Glendale, California, United States
- Teva Investigational Site 10738
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- The subject is able to read, speak, and write in English or Japanese, as applicable.
- The subject is able to understand and be willing to comply with the study requirements (eg, all dietary, exercise, tobacco, and alcohol restrictions) and provide written informed consent to participate in the study.
- The subject is a man or woman, 20 to 50 years of age, inclusive.
- The subject has a body mass index (BMI) of 18.0-28.0 kg/m2, inclusive.
- The subject is in a good health, as determined by medical history, ECG, vital signs, physical examination, and clinical laboratory tests.
- If female and of childbearing potential, the subject must have a negative β-hCG test at screening and a negative urine human chorionic gonadotropin (HCG) test at check-in and be willing and able to use one of the following medically acceptable double barrier methods of birth control from the screening visit through the end-of-study visit: non-hormonal intrauterine device with condom, diaphragm with condom, or condom with spermicide. Female subjects who are postmenopausal (1 year since last menses) must have elevated follicle stimulating hormone (FSH) level above 35 U/L, or be surgically sterile.
- The subject must complete the screening process within 4 weeks before study drug administration.
The subject must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation, as specified in this protocol.
Additional inclusion criteria for Japanese subjects:
- The subject was born in Japan and holds a valid Japanese passport.
- The subject has 2 Japanese parents and 4 Japanese grandparents, as confirmed by interview.
The subject has been living outside of Japan for 10 years or fewer as confirmed by interview.
Additional inclusion criterion for Caucasian subjects:
- The subject has no parents or grandparents of Japanese descent as confirmed by interview.
Exclusion Criteria:
- The subject is a woman who is pregnant or lactating.
- The subject has significant food or drug allergies or a known allergy or sensitivity to rasagiline or its derivatives or the formulation excipients.
- The subject is unwilling to refrain from vigorous exercise (eg, strenuous or unaccustomed weight lifting, running, bicycling, etc) from 7 days before the first day of study drug administration until the final assessment.
The subject has had 1 of the following conditions in the noted amount of time before screening or at any time between screening and the first day of study drug administration:
- major trauma or surgery in the last 2 months
- acute infection in the last 2 weeks
- malignancy within the last 5 years
- The subject has a history of tuberculosis.
- The subject has any condition that may interfere with drug absorption, distribution, metabolism, or excretion.
- The subject is suffering from, or has a clinically significant history of, 1 or more of the following: cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), or a history of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject if he or she participates in the study.
- The subject has a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
- The subject has a history of hypertension or occasional increase of blood pressure, or any history of vascular structural abnormality.
- The subject has a sitting blood pressure outside the range of 80 to 139 mm Hg (systolic) or 45 to 89 mm Hg (diastolic) (after at least a 5-minute rest) measured at screening. Blood pressure may be retested twice at intervals of 5 minutes. The blood pressure is considered sustained if either the systolic or diastolic pressure exceeds the stated limits in all 3 assessments.
The subject has used 1 of the following prohibited drugs or foods:
- an investigational drug (new chemical entity) during the month prior to the first day of study drug administration
- antidepressants, including selective serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, within 42 days before the first day of study drug administration
- MAO inhibitors, including reserpine and methyldopa, within 3 months prior to the first day of study drug administration
- any medications (including over-the-counter [OTC] medications, vitamins, or herbal or nutritional supplements) within 14 days before the first day of study drug administration (except paracetamol/acetaminophen or ibuprofen used occasionally, up to 24 hours before the first day of study drug administration)
- drugs known to significantly inhibit CYP1A enzyme drug metabolism within 14 days before the first day of study drug administration or drugs known to significantly induce human cytochrome P enzyme (CYP)1A drug metabolism within 28 days before the first day of study drug administration
- excessive amounts of alcohol, defined as more than 3 drinks of alcoholic beverages (eg, beer, wine, or distilled spirits) per day in the last 3 months before the first day of study drug administration or a history of alcohol abuse
- excessive amounts (equivalent to more than 6 cups of brewed coffee per day) of coffee, tea, cola, or other caffeinated beverages in the 3 months before the first day of study drug administration
- grapefruit, Seville oranges, pomelo, or products made from them within 14 days before the first day of study drug administration until after the last day of pharmacokinetic sampling.
- Other exclusion criteria apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Rasagiline
Rasagiline mesylate oral tablets (AZILECT®) are provided at dose strengths of 0.5 and 1 mg (based on rasagiline base).
Rasagiline oral tablets will be dispensed for 10 consecutive days of treatment.
The oral dose will be administered each day with 240 mL water at room temperature after an overnight fast of at least 10 hours.
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Each subject will be enrolled into 1 of 4 cohorts:
Each subject will then be randomly assigned to 1 of the following groups:
Other Names:
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PLACEBO_COMPARATOR: Placebo
Placebo tablets match in size and appearance to rasagiline tablets for each dose strength.
Placebo tablets will be dispensed for 10 consecutive days of treatment.
The oral dose will be administered each day with 240 mL water at room temperature after an overnight fast of at least 10 hours.
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Each subject will be enrolled into 1 of 4 cohorts:
Each subject will then be randomly assigned to 1 of the following groups:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Cmax
Time Frame: At Baseline through Day 10
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At Baseline through Day 10
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Tmax
Time Frame: At Baseline through Day 10
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At Baseline through Day 10
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AUC from time 0 to the time of the last measurable drug concentration (AUC0-t)
Time Frame: At Baseline to Day 1
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AUC 0-t will be calculated after administration of a single dose of rasagiline.
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At Baseline to Day 1
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AUC from time 0 to infinity (AUC∞)
Time Frame: At Baseline to Day 1
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AUC∞ will be calculated after administration of a single dose of rasagiline.
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At Baseline to Day 1
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Percentage extrapolated AUC (%AUCext)
Time Frame: At Baseline to Day 1
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%AUCext will be calculated after administration of a single dose of rasagiline.
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At Baseline to Day 1
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Apparent plasma terminal elimination rate constant (λz)
Time Frame: At Baseline to Day 10
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At Baseline to Day 10
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Associated elimination half life (t½)
Time Frame: At Baseline to Day 10
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At Baseline to Day 10
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AUC over the dosing interval at steady state (AUCτ)
Time Frame: At Baseline to Day 10
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At Baseline to Day 10
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Minimum measured plasma concentration at steady state by inspection (Cmin,ss)
Time Frame: From Baseline to Day 10
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minimum measured plasma concentration at steady state by inspection (Cmin,ss) (multiple dose [predose concentrations on days 8 and 9]))
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From Baseline to Day 10
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Average plasma concentration at steady state (Cav,ss)
Time Frame: From Baseline to Day 10
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The average plasma concentration at steady state (Cav,ss) is obtained by the calculation: AUCτ/τ, where tau is the dosing interval |
From Baseline to Day 10
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Fluctuation at steady state
Time Frame: From Baseline to Day 10
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Fluctuation at steady state, calculated as (Cmax,ss-Cmin,ss)/Cav,ss
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From Baseline to Day 10
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Steady-state accumulation ratio (Rss)
Time Frame: From Baseline to Day 10
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Steady-state accumulation ratio (Rss) calculated as (AUCτ/AUC∞)
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From Baseline to Day 10
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Apparent total body clearance (CL/F)
Time Frame: From Baseline to Day 10
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From Baseline to Day 10
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Apparent total volume of distribution (V/F)
Time Frame: From Baseline to Day 10
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From Baseline to Day 10
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Concentrations of 1-aminoindan
Time Frame: Day 1 to Day 11
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The concentrations of rasagiline major metabolite, 1-aminoindan, in plasma will be calculated, if possible.
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Day 1 to Day 11
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Peripheral monoamine oxidase B (MAOB)
Time Frame: Day 1 to Day 11
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The pharmacodynamics of rasagiline will be assessed by measuring the extent of peripheral monoamine oxidase B (MAOB) inhibition after multiple-dose administration of rasagiline, calculated as the percentage of the baseline platelet MAO-B activity.
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Day 1 to Day 11
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Occurrence of Adverse Events
Time Frame: From informed consent signing to end of study (Day 12)
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Adverse events, clinical laboratory test results, vital signs measurements, physical examinations, 12- lead electrocardiogram (ECG) findings, and use of concomitant medications will be assessed throughout the study.
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From informed consent signing to end of study (Day 12)
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Neuroprotective Agents
- Protective Agents
- Monoamine Oxidase Inhibitors
- Rasagiline
Other Study ID Numbers
- TVP1012-PK-10002
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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