To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of CC-220 in healthy subjects and to evaluate the relative bioavailability of a formulated CC-220 capsule
This is a 3-part study to be conducted at a single study center. Part 1 is a randomized, double-blind, placebo-controlled, ascending-dose study. During the course of Part 1, each subject will participate in a screening phase, a baseline phase, a treatment phase and a follow up visit. There will be a total of 4 cohorts, each of which consists of a different dose level and/or dosing duration, with 8 or 9 subjects per cohort. In each cohort, 6 subjects will receive a dose of CC-220 and the remaining subjects will receive placebo depending on the randomization schedule. In 2 of the cohorts, study drug will be administered once daily for a total of 14 days. In the other 2 cohorts, study drug will be administered once daily for 28 days. In one of the 28-day dosing cohorts, 2 vaccinations (tetanus toxoid adsorbed and pneumococcal vaccinations) will also be administered on Day 14 of the 28-day dosing period to help characterize the effect of CC-220 on antibody responses. Part 2 is a randomized, double-blind, placebo-controlled, parallel-group study to explore the effects of an alternative dosing schedule on the pharmacodynamics of CC-220. During the course of Part 2, each subject will participate in a screening phase, a baseline phase, a treatment phase and a follow up visit. There will be a total of 2 cohorts, each of which consists of a different dose level, with 9 subjects per cohort. In each cohort, 6 subjects will receive a dose of CC-220 and 3 subjects will receive placebo depending on the randomization schedule. The dosing frequency will be either once every 3 days for 14 days or once every 7 days for 28 days. Part 3 is a randomized, open-label, two-period, two-way crossover study to evaluate the relative bioavailability of one CC-220 formulated capsule, relative to two reference capsules, following a single oral dose of CC-220. During the course of Part 3, each subject will participate in a screening phase, a baseline phase, a treatment phase consisting of 2 periods, and a follow up visit. There will be one cohort consisting of a total of 12 subjects. In each study period, approximately 6 subjects will receive a single dose of CC-220 as one formulated capsule (test product) and approximately 6 subjects will receive a single dose of CC-220 as two reference capsules (reference product).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
DOUBLE
Enrollment
64
Covance Clinical Research Unit
Madison, Wisconsin, United States
Adverse Events
Number of participants with adverse events
Time frame: Up to 7 months overall
Concentrations of CC-220 and its R-enantiomer in plasma
Blood samples will be collected at pre-specified times to determine levels of CC-220 and its R-enantiomer in plasma
Time frame: Up to 30 days per cohort
Pharmacodynamic Assessmens
Blood samples will be collected at pre-specified times for pharmacodynamic assessments
Time frame: Up to 42 days per cohort
Pharmacokinetics - Cmax
Maximum observed plasma concentration
Time frame: Up to 30 days
Pharmacokinetics - tmax
Time to Cmax
Time frame: Up to 30 days
Pharmacokinetics - AUCinf
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Time frame: Up to 30 days
Pharmacokinetics - AUCt
Area under the plasma concentration-time curve from time zero to the last quantifiable concentration
Time frame: Up to 30 days
Pharmacokinetics - AUCtau
Area under the plasma concentration-time curve from time zero to tau, where tau is the dosing interval
Time frame: Up to 30 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
CC-220 1mg will be administered once daily for 7 days on 2 separate occasions, with a 7-day washout in between, for a total of 14 days of dosing
Placebo will be administered once daily for up to 28 days
CC-220 0.3mg will be administered every 3 days for 14 days (5 total doses)
CC-220 1mg (once every 7 days for 28 days)
CC-220 1mg will be administered as a single dose in each of 2 study periods; once as a formulated capsule and once as two reference capsules
Pharmacokinetics - t1/2,z
Terminal-phase elimination half-life
Time frame: Up to 30 days
Pharmacokinetics - CL/F
Apparent total plasma clearance when dosed orally
Time frame: Up to 30 days
Pharmacokinetics - Vz/F
Apparent total volume of distribution when dosed orally, based on the terminal phase
Time frame: Up to 30 days
Accumulation Ratio (RA)
Accumulation Ratio for Cmax and AUCtau
Time frame: Up to 30 days