A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Rasagiline

NCT01879748 | Completed Phase 1

• 1 other identifier: TVP1012-PK-10002
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the pharmacokinetics of rasagiline in healthy Japanese and Caucasian subjects after single and multiple doses of rasagiline.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Azilect; rasagiline mesylate

Outcome Measures

Primary Outcomes (14)

• Cmax

  At Baseline through Day 10

• Tmax

  At Baseline through Day 10

• AUC from time 0 to the time of the last measurable drug concentration (AUC0-t)

  AUC 0-t will be calculated after administration of a single dose of rasagiline.

  At Baseline to Day 1

• AUC from time 0 to infinity (AUC∞)

  AUC∞ will be calculated after administration of a single dose of rasagiline.

  At Baseline to Day 1

• Percentage extrapolated AUC (%AUCext)

  %AUCext will be calculated after administration of a single dose of rasagiline.

  At Baseline to Day 1

• Apparent plasma terminal elimination rate constant (λz)

  At Baseline to Day 10

• Associated elimination half life (t½)

  At Baseline to Day 10

• AUC over the dosing interval at steady state (AUCτ)

  At Baseline to Day 10

• Minimum measured plasma concentration at steady state by inspection (Cmin,ss)

  minimum measured plasma concentration at steady state by inspection (Cmin,ss) (multiple dose \[predose concentrations on days 8 and 9\]))

  From Baseline to Day 10

• Average plasma concentration at steady state (Cav,ss)

  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

• Fluctuation at steady state

  Fluctuation at steady state, calculated as (Cmax,ss-Cmin,ss)/Cav,ss

  From Baseline to Day 10

• Steady-state accumulation ratio (Rss)

  Steady-state accumulation ratio (Rss) calculated as (AUCτ/AUC∞)

  From Baseline to Day 10

• Apparent total body clearance (CL/F)

  From Baseline to Day 10

• Apparent total volume of distribution (V/F)

  From Baseline to Day 10

Secondary Outcomes (3)

• Concentrations of 1-aminoindan

  Day 1 to Day 11

• Peripheral monoamine oxidase B (MAOB)

  Day 1 to Day 11

• Occurrence of Adverse Events

  From informed consent signing to end of study (Day 12)

Study Arms (2)

Rasagiline

EXPERIMENTAL

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.

Drug: Rasagiline

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Rasagiline DRUG

Each subject will be enrolled into 1 of 4 cohorts: * cohort 1 (16 Japanese subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo * cohort 2 (16 Caucasian subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo * cohort 3 (16 Japanese subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo * cohort 4 (16 Caucasian subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo Each subject will then be randomly assigned to 1 of the following groups: * rasagiline at 0.5 mg (8 Japanese and 8 Caucasian subjects) * rasagiline at 1 mg (8 Japanese and 8 Caucasian subjects) * rasagiline at 2 mg (8 Japanese and 8 Caucasian subjects) * placebo (8 Japanese and 8 Caucasian subjects)

Also known as: rasagiline mesylate, TVP1012, AZILECT®

Rasagiline

Placebo DRUG

Each subject will be enrolled into 1 of 4 cohorts: * cohort 1 (16 Japanese subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo * cohort 2 (16 Caucasian subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo * cohort 3 (16 Japanese subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo * cohort 4 (16 Caucasian subjects): 4 subjects each for 0.5, 1, and 2 mg of rasagiline and placebo Each subject will then be randomly assigned to 1 of the following groups: * rasagiline at 0.5 mg (8 Japanese and 8 Caucasian subjects) * rasagiline at 1 mg (8 Japanese and 8 Caucasian subjects) * rasagiline at 2 mg (8 Japanese and 8 Caucasian subjects) * placebo (8 Japanese and 8 Caucasian subjects)

Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• The subject has no parents or grandparents of Japanese descent as confirmed by interview.

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (1)

Teva Investigational Site 10738

Glendale, California, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

rasagiline

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2013
• First Posted: June 18, 2013
• Study Start: June 1, 2013
• Primary Completion: September 1, 2013
• Study Completion: November 1, 2013
• Last Updated: December 20, 2013

Record last verified: 2013-12

Locations

US (1)