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Cc-486

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Two 150-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of CC-486 on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.

One 300-mg tablet of oral CC-486 under fasting condition on PK dosing Day 1, followed by one 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.

One 300-mg tablets of CC-486 under fasting condition on PK dosing Day 1, followed by two 150-mg tablets on PK dosing Day 2; If PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine for Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.

One 300-mg tablet of oral CC-486 under fed condition on PK dosing Day 1, followed by one tablet of 300-mg oral CC-486 under fasted conditions on PK dosing Day 2; if PI chooses to treat the patient in the extension phase with Azacitidine, Vidaza (Azacitidine of Injection) 75 mg/m2 intravenously (IV) or subcutaneously (SC) daily x 7 days every 4 weeks for less than or equal to 6 (28-day) cycles will be administered.

Arm 1: Two 150-mg tablets of CC-486 on Day 1 and 1 x 300 mg CC-486 on Day 2 Arm 2: 1 x 300mg tablet of CC 486 on Day 1 and 2 x 150mg CC-486 on Day 2

CC-486

75mg/m\^2 IV or SC daily x 7 days every 4 weeks for ≤ 6 (four-week) cycles

Vidaza

Du Lam, MD

This is a Phase 1, open-label, multicenter, randomized, 2-stage crossover study consisting of 2 phases:

Stage I - Pharmacokinetics (Bioequivalence), with an Extension Stage II - Pharmacokinetics (Food Effect) with an Extension

This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the US and 2 in Canada will participate in this study.

Stage I - Pharmacokinetics (Bioequivalence)

Subjects will be randomized to receive CC-486 300 mg orally on each of the two pharmacokinetic (PK) study days based on the dosing sequences they are randomized to:

Dosing Sequence 1: 2x150 mg tablets followed by 1x30 mg tablet. Dosing Sequence 2: 1x300 mg tablet followed by 2x150 mg tablets. Each dose will be administered in the clinic at least 48 hours apart between PK dosing day 1 and PK dosing day 2 over a period no longer than 10 days under fasted conditions.

Stage II - Pharmacokinetics (Food Effect)

Subjects will be randomized to receive CC-486 300 mg orally on each of the two PK study days based on the dosing sequences they are randomized to:

Dosing Sequence 1: 1x300 mg tablet under fasted condition followed by 1x300 mg tablet under fed condition.

Dosing Sequence 2: 1x300 mg tablet under fed condition followed by 1x300 mg tablet under fasted condition.

Each dose will be administered in the clinic at least 48 hours apart between PK dosing day 1 and PK dosing day 2 over a period no longer than 10 days. The sponsor will generate the randomization scheme and assign subjects upon enrollment to the appropriate sequence for dosing:

Fasted condition: following an overnight fast of at least 10 hours, subjects will ingest oral Azacitidine with 240 mL of room temperature water. Subjects must fast for a minimum of 4 hours following oral Azacitidine administration. Subjects may drink water as desired, except for 1 hour before and 1 hour after oral Azacitidine administration.

Fed condition: following an overnight fast of at least 10 hours and following the performance of all required pre-dose assessments, subjects randomized to receive test medication in a fed state will begin ingesting a breakfast meal 30 (±5) minutes prior to the planned administration of oral Azacitidine. They will continue the entire meal within 20 to 25 minutes (no less than 20 minutes) from the time the meal is served. Subjects will then ingest oral Azacitidine with 240 mL of room temperature water. Subjects must fast a minimum of 4 hours following oral Azacitidine administration. Subjects may drink water as desired, except for 1 hour before and 1 hour after administration of oral Azacitidine.

Extension Phase (for subjects who have completed PK Stage I or Stage II) Subjects continuing beyond the pharmacokinetics phase (Stage I or Stage II) will enter the extension phase of the study at the discretion of the investigator to receive \< 6 (four-week) cycles of Vidaza 75 mg/m2 IV or SC daily for 7 days in the clinic and repeat every 4 weeks per prescribed label at the discretion of the investigator for ≤ 6 (four-week) cycles.

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

A Phase 1, Open-label, Multicenter, Randomized, 2-Period, Crossover Study to Evaluate the Bioequivalence and Food Effect Bioavailability of CC-486 (Oral Azacitidine) Tablets in Adult Cancer Subjects

The observed time to first maximum concentration

Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule

Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = \[AUCt + Ct/λz\]. Ct is the last quantifiable concentration

Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear concentration-time curve

Terminal phase half-life, calculated according to the following equation: t½ = 0.693/λz

Apparent total clearance, calculated as Dose/AUC∞

Apparent volume of distribution, calculated according to the equation: Vd/F = (CL/F) / λz

Area under the concentration-time curve from time zero to the last quantifiable time point calculated by the linear trapezoidal rule.

Area under the concentration time-curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity. It will be calculated as AUC∞ = \[AUCt + Ct/λz\]. Ct is the last quantifiable concentration.

Adverse Event (AE) is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.

Celgene

Spots Global Cancer Trial Database for soli tumor malignancy