Vitamin E δ-Tocotrienol Multiple Dose in Healthy Subjects
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Vitamin E δ-Tocotrienol Following Multiple Dose Administration in Healthy Subjects|
- Number of Participants With Treatment Related Adverse Events [ Time Frame: 3 Weeks Per Participant ] [ Designated as safety issue: Yes ]The primary objective of this study is to evaluate the safety and tolerability of Vitamin E δ-Tocotrienol and to determine the maximum administered dose (MAD) or maximum tolerated dose (MTD) of Vitamin E δ-Tocotrienol administered twice daily for 14 days. Safety analyses and summary tables will include data collected for all subjects who receive at least one dose of study drug.
- Maximum Plasma Concentration (Cmax) of Vitamin E δ-Tocotrienol [ Time Frame: 3 Weeks Per Participant ] [ Designated as safety issue: No ]To determine the effects of dose on the plasma pharmacokinetic (PK) of Vitamin E δ-Tocotrienol following multiple dose administration in healthy subjects.
- Pharmacodynamic (PD) Markers of Vitamin E δ-Tocotrienol Activity in Peripheral Blood [ Time Frame: Day 1, Day 8 Day 14 ] [ Designated as safety issue: No ]Peripheral blood mononuclear cells will be collected at each time point for examination of biomolecular markers not limited to Erk, p-Erk, AKT, p-AKT, p27, Ki-67, and exportin.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||April 2016|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Experimental: Phase I Dose Escalation
Each investigator will be provided with adequate supplies of Vitamin E δ -Tocotrienol, which will be supplied as 100-mg, 200-mg, and 400-mg capsules. Vitamin E δ-Tocotrienol will be administered orally once. The dose administered to each subject will be fixed and based on cohort assignment. Doses will be administered at the clinical site during each protocol-defined visit.
Drug: Vitamin E δ-Tocotrienol
Vitamin E δ-Tocotrienol will be administered orally as a single agent twice daily for 14 consecutive days. Vitamin E δ-Tocotrienol is supplied as 100-mg, 200-mg, and 400-mg capsules. The first cohort will be dosed with δ-tocotrienol at 100 mg twice daily for 14 consecutive days. A minimum of 3 subjects is planned for each dosing cohort with Vitamin E δ-Tocotrienol dose escalation dependent on safety and available PK data from prior cohorts. At the MTD or MAD, 18 subjects will be enrolled.
Other Name: Delta-tocotrienol
Participants will be accrued in cohorts of three. The decision to dose escalate will be made by the Cohort Review Committee (CRC) based on safety after the last subject in the current cohort has completed the Study Treatment Period. The study will consist of the following procedures:
- Pre-Treatment Period: The screening period must occur within 7 days of dosing.
- Study Treatment Period (14 days): Vitamin E δ-Tocotrienol will be administered orally twice daily for 14 consecutive days
- Post-Treatment Period: Subject will return to the study site 7 days after the dose of Vitamin E δ-Tocotrienol for an end-of-treatment assessment. On day 8 (± 2 days) after the last dose of study drug, the investigator will obtain follow-up information. Any serious adverse events (SAEs) present at 7 days after the last dose and possibly related to study drug will be followed until resolution, stabilization, or initiation of treatment that confounds the ability to assess the event.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01450046
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Amit Mahipal, M.D.||H. Lee Moffitt Cancer Center and Research Institute|