Evaluate the Pharmacokinetics of CC-220 in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared With Healthy Subjects

Subjects must satisfy all of the following criteria to be enrolled in the study:

1. Subject must understand and voluntarily sign an Informed Consent Form (ICF) prior to any study-related assessments/procedures being conducted.

2. Subject is willing and able to adhere to the study visit schedule and other protocol requirements, including the restrictions.

3. Subject is a male or female ≥ 18 and ≤ 70 years of age at the time of signing the ICF.

4. Subject has body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at Screening.

5. Subject agrees to abide by the requirements and restrictions outlined in the CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.

6. Female subjects NOT of childbearing potential must:

a. Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation required) at least 6 months before Screening, or postmenopausal (defined as 24 consecutive months without menses before Screening, with a follicle-stimulating hormone \[FSH\] level of \> 40 IU/L at Screening).

7. Females of childbearing potential (FCBP)1 must have a negative pregnancy test at the Screening and baseline visits. All FCBP must use two effective birth control methods at the same time (for example: birth control pills, condoms, etc.) or practice complete abstinence from sexual contact with a man beginning 28 days before starting study treatment, throughout the entire duration of study treatment and at least 28 days after the end of study treatment with CC-220. The 2 methods of reliable contraception must include 1 highly effective method and 1 additional effective (barrier) method; options are described below:

Examples of highly effective methods: intrauterine device; hormonal (birth control pills, injections, implants, levonorgestrel-releasing intrauterine system, medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills \[eg, desogestrel\]); tubal ligation; or partner's vasectomy.

AND Examples of additional effective methods: Male condom, diaphragm, or cervical cap.

8. Male subjects must:

a. Practice true abstinence2 (which must be reviewed on a monthly basis, as applicable, and source documented) or agree to use a barrier method of birth control (condoms not made out of natural \[animal\] membrane \[latex condoms are recommended\]) during sexual contact with a pregnant female or FCBP while participating in the study, and for at least 90 days after the dose of IP, even if he has undergone a successful vasectomy.

9. Subject has clinical laboratory safety test results that are within normal limits or acceptable to the Investigator.

10. Subject is afebrile (febrile is defined as ≥ 38°C or 100.4°F), with sitting systolic blood pressure ≥ 90 and ≤ 160 mm Hg, sitting diastolic blood pressure ≥ 50 and ≤ 100 mm Hg, and pulse rate ≥ 40 and ≤ 100 beats per minute at Screening.

Each subject with mild, moderate, or severe hepatic impairment must also meet all of the criteria listed below for entry:

11. Subject has mild, moderate, or severe hepatic impairment or cirrhosis due to chronic hepatic disease and/or prior alcohol abuse.

12. Subject has creatinine less than or equal to 1.5 x ULN.

13. Subject has mild (Group 1), moderate (Group 2), or severe (Group 3) hepatic impairment as defined by Child-Pugh score.

* Group 1 subjects (mild hepatic impairment) are required to have documentary confirmation of the diagnosis of liver impairment made by biopsy, laparoscopy, or ultrasound with a Child-Pugh score of ≥ 5 to ≤ 6 at Screening.

* Group 2 subjects (moderate hepatic impairment) are required to have documentary confirmation of the diagnosis of liver impairment made by biopsy, laparoscopy, or ultrasound with a Child-Pugh score of ≥ 7 to ≤ 9 at Screening.

* Group 3 subjects (severe hepatic impairment): if biopsy, laparoscopy, or ultrasound is not performed prior to Screening, subjects can be included only if they have chronic liver disease and objective evidence of portal hypertension (ascites diagnosed by imaging or varices), with a Child-Pugh score ≥ 10 and ≤ 13 at Screening.

Subjects should be enrolled into the group corresponding to the Child-Pugh classification score that most accurately reflects the most severe hepatic disease classification within the past 6 months (based on past medical history or PE observation).

Note: If a Child-Pugh score was previously calculated and documented in the last 6 months, and it is more severe than the one calculated at Screening, then that previous value may be used for study entry purposes. If the Screening Child-Pugh score is more severe, then it will be used. If no score was calculated in the 6 months prior to Screening, then the score obtained at Screening will be used. Adequate documentation should be provided to substantiate the Child-Pugh score assigned to each subject.

14. Subject must be medically stable for at least 1 month before Screening with clinically acceptable medical history, PEs, clinical laboratory results, vital signs, and 12-lead ECGs consistent with the underlying hepatic impairment condition, as judged by the Investigator.

15. Subject is stable on a concomitant medication regimen (defined as not starting a new medication\[s\] or a change in the dosage or frequency of the concomitant medication\[s\] within 7 days or 5 half-lives \[whichever is longer\] before dosing with CC-220).

16. Subject may be treated with diuretics for ascites; however, subjects with severe ascites at time of enrollment may only be included at the discretion of the Investigator with agreement of Celgene.

17. Subject may have a history of encephalopathy; however, they must be on stable treatment for at least 1 month prior to Screening and must not have had an acute severe encephalopathic episode in the 1 month prior to Screening.

18. Subject has a normal or clinically acceptable 12-lead ECG at Screening (QT interval corrected for heart rate using Fridericia's formula \[QTcF\] ≤ 480 msec).

Each matched healthy subject must also meet all the criteria listed below for entry:

19. Subject is free of any CS disease that would interfere with the study evaluations and has not had any unstable CS illness within 3 months prior to Screening.

20. Subject has liver-related laboratory test results within the respective reference ranges or with clinically insignificant excursions therefrom as agreed by the Investigator and Celgene's Medical Monitor.

21. Subject must match a subject in Group 2 or 3, as needed, primarily with respect to sex, age (± 10 years) and weight (± 13.6 kg \[30 pounds\]). Group 4 subjects will be matched with subjects from Group 2, and Group 5 subjects will be matched with Group 3 subjects.

22. Subject is in good health as determined by past medical history, PEs, vital signs, ECG, and clinical laboratory results. Clinical laboratory results (ie, hematology, chemistry, and urinalysis) and 12-lead ECGs must be within normal limits or clinically acceptable as judged by the Investigator. In addition:

1. If male, subject has a QTcF value ≤ 440 msec at Screening.

2. If female, subject has a QTcF value ≤ 460 msec at Screening.

What this study is about