Study to Evaluate Pharmacokinetics of Pomalidomide in Hepatically Impaired Males
Study to Evaluate Pharmacokinetics of Pomalidomide in Hepatically Impaired Males
This study is for research purposes only and will not treat any disease or condition you may
 have. The study is an open label and single dose study; open label means that you, the study
 doctor and study staff will know which study drug you are taking.

 The purpose of this research study is to compare drug levels in the body of people with liver
 disease to drug levels in healthy people with a normal liver. In addition, the safety of the
 study drug will be studied. Information about any side effects (discomfort or decline in
 health) that may happen will be collected. The study drug will be given by mouth to subjects
 with liver disease and to healthy subjects.

 In the body, drugs are normally removed by the liver with a smaller amount being removed by
 the kidneys. When the liver is not working as well as it should, the body may not be able to
 remove drugs from the body quickly.

 The information from this study will be used to decide if the drug is safe in subjects with
 liver disease or if a lower dose of the study drug would be safer.
The study will be conducted at more than one clinical site (2-3 clinical research sites) and
 designed to assess the impact of severe liver disease or hepatic impairment (Part 1, Group 1)
 on the PK of pomalidomide following oral administration of a single dose of 4 mg pomalidomide
 (the study drug). The study drug, pomalidomide (POMALYST®), has been approved by the United
 States Food and Drug Administration (FDA) to treat patients with multiple myeloma (MM).
 Patients with MM have bone marrow that produces a large number of abnormal cells.
 Pomalidomide is only available by prescription.

 Since participants in this study do not have MM, pomalidomide is considered experimental for
 the purposes of this research study. Throughout this form, pomalidomide will be referred to
 as "the study drug."

 Participation in this study will be in either the healthy group or the group with liver
 disease. For the group with the liver disease,the liver disease will be graded by the study
 doctor as being "severe," "moderate," or "mild." This will be done by the study doctor
 depending on medical history, physical examination, laboratory tests, and certain previous
 results of liver scans or liver biopsy.

 The amount of the study drug in blood will be measured at certain times to how well the drug
 is broken-down or removed from the body. Blood samples approximately 1 teaspoon
 (approximately 5-6 mL) will be collected 13 times the following times to measure study drug
 levels in your blood:

 • Predose (just before dosing), and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, and 48 hours
 after dose pomalidomide morning dose on Day 1.

 This study will have two parts:

 Part 1 will evaluate the study drug in subjects with severe liver disease (Group and healthy
 volunteer subjects (Group 1) matched to the subjects with liver disease. Part 2 will evaluate
 the study drug in subjects with moderate (Group 3) and/ mild (Group 4) liver disease.

 Study participation will be in one part only (either Part 1 or Part 2). Part be conducted
 after the data from Part 1 is analyzed and reviewed and the doctor and the sponsor determine
 that there is a need to conduct Part 2.

 The purposes of this study are:

 -  To measure and compare the levels of pomalidomide in the blood of male subjects with
 severe liver disease and their matched healthy volunteer subjects after taking one 4-mg
 capsule of pomalidomide.

 -  To measure and compare the levels of pomalidomide in the blood of male subjects with
 moderate or mild liver disease after taking one 4-mg capsule of pomalidomide.

 -  To study the impact of liver disease on the safety of a single dose of pomalidomide in
 male subjects with liver disease.

 Approximately 16 male subjects will be enrolled in Part 1 of the study (8 healthy subjects
 and 8 subjects with severe liver disease). Approximately 16 male subjects will be in Part 2
 of the study (8 subjects with mild liver disease and subjects with moderate liver disease).
 If both parts of the study are completed, a total of about 32 male subjects will be enrolled.
 The total time a participant will be in the study is about 1 month (from screening visit to
 end of study).
Inclusion Criteria:

 -  Inclusion Criteria for Matched Healthy Subjects (Group 1):

 1. Must understand and voluntarily sign a written informed consent document (ICD)
 prior to any study-related procedures being performed.

 2. Must be able to communicate with the investigator, understand and comply with the
 requirements of the study, and agree to adhere to restrictions and examination
 schedules.

 3. Must be male subjects of any race between 18 to 70 years of age, inclusive, with
 a body mass index between 18 and 37 kg/m2 (inclusive).

 4. Subjects must be in good health (at screening and baseline [Day -1]) as
 determined by the investigator on the basis of medical history, physical
 examination, clinical laboratory safety test results, vital signs, and 12 lead
 ECG.

 5. Clinical laboratory safety tests must be within normal limits or acceptable to
 the investigator (at screening and baseline [Day -1]), and in particular:

 a. Creatinine less than or equal to 1.5x upper limit of normal (ULN)

 6. Must be afebrile, with supine (after the subject has rested for at least 5
 minutes) systolic blood pressure: 90 to 140 mmHg, supine diastolic blood
 pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm.

 7. Must have a normal or clinically acceptable 12-lead ECG. Male subjects must have
 a QTcF value ≤ 430 msec.

 8. Subjects (with or without vasectomy) must practice true abstinence* or agree to
 use double barrier contraception (ie, latex condom or any non-latex condom not
 made out of natural [animal] membrane [eg, polyurethane]) and one other method
 (eg, spermicide) when engaging in sexual activity with woman of child-bearing
 potential during study conduct, and for 28 days after the last dose of study
 medication.

 * True abstinence is acceptable when this is in line with the preferred and usual
 lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation,
 symptothermal, postovulation methods) and withdrawal are not acceptable methods
 of contraception.

 9. Must agree to refrain from donating sperm, blood or plasma (other than for this
 study) while participating in this study and for at least 28 days after the last
 dose of study drug.

 10. Subjects who have not performed strenuous physical activity for at least 72 hours
 prior to the dose of study drug and agree to not engage in strenuous physical
 activity throughout the study and until study completion (follow-up safety
 telephone call).

 11. Will be counseled about pregnancy precautions and risks of fetal exposure and
 agree to comply with the conditions described in the counseling document.

 Inclusion Criteria for All Hepatically Impaired Subjects (Groups 2, 3 and 4):

 1. Must understand and voluntarily sign a written informed consent form (ICF) prior to
 any study-related procedures being performed.

 2. Must be able to communicate with the investigator, understand and comply with the
 requirements of the study, and agree to adhere to restrictions and examination
 schedules.

 3. Male subjects of any race between 18 to 70 years of age, inclusive, with a body mass
 index between 18 and 37 kg/m2 (inclusive).

 4. Subjects must have severe, moderate, or mild hepatic impairment or cirrhosis due to
 chronic hepatic diseases and/or prior alcohol abuse (Groups 2, 3 and 4, respectively).

 5. Creatinine less than or equal to 1.5X ULN.

 6. 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 upon past medical history or physical
 examination observations). Adequate documentation should be provided to substantiate
 the Child-Pugh score assigned to each subject.

 1. For Group 2 (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.

 2. Subjects in Group 3 (moderate hepatic impairment) are required to have
 confirmation of the diagnosis of cirrhosis made by biopsy, laparoscopy or
 ultrasound with a Child-Pugh score of 7 to 9, inclusive.

 3. Subjects in Group 4 (mild hepatic impairment) are required to have confirmation
 of the diagnosis of cirrhosis made by biopsy laparoscopy or ultrasound with a
 Child- Pugh score of 5 to 6, inclusive.

 7. Subjects 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 the Sponsor.

 8. Subjects must not have history of hepatorenal syndrome or hemolysis.

 9. Subjects (with or without vasectomy) must practice true abstinence* or agree to use
 double barrier contraception (ie, latex condom or any non-latex condom not made out of
 natural [animal] membrane [eg, polyurethane]) and one other method (eg, spermicide)
 when engaging in sexual activity with woman of child-bearing potential during study
 conduct, and for 28 days after the last dose of study medication.

 * True abstinence is acceptable when this is in line with the preferred and usual
 lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal,
 post-ovulation methods) and withdrawal are not acceptable methods of contraception].

 10. Must agree to refrain from donating sperm, blood or plasma (other than for this study)
 while participating in this study and for at least 28 days after the last dose of
 study drug.

 11. Will be counseled about pregnancy precautions and risks of fetal exposure and agree to
 comply with the conditions described in the counseling document .

 12. Subjects are medically stable for at least 1 month before pomalidomide administration
 with clinically acceptable physical exam, clinical lab tests, vital signs, and 12-lead
 ECG consistent with the underlying stable mild, moderate or severe impaired liver
 condition as judged by the investigator.

 13. Subjects must be free of acute major illness within one month prior to dosing or acute
 illness within 14 days prior to dosing, with the exception of hepatic impairment and
 related illnesses as judged by the investigator.

 14. Subjects who have not performed strenuous physical activity for at least 72 hours
 prior to the dose of study drug and agree to not engage in strenuous physical activity
 throughout the study and until study completion (follow-up safety telephone call).

 Exclusion Criteria:

 -  Exclusion Criteria for Matched Healthy Subject (Group 1)

 1. History of any clinically significant and relevant neurological,
 gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary,
 metabolic, endocrine, hematological, allergic disease, drug allergies, known
 hypersensitivity to a member of the class of IMiDs, or other major disorders.

 2. Any condition which places the subject at unacceptable risk if he were to
 participate in the study, or confounds the ability to interpret data from the
 study.

 3. Used any prescribed systemic or topical medication within 30 days of the first
 dose administration, unless Sponsor agreement is obtained.

 4. Used any non-prescribed systemic or topical medication (including vitamin/mineral
 supplements, and herbal medicines) within 14 days of the first dose
 administration, unless Sponsor agreement is obtained.

 5. Has any surgical or medical conditions possibly affecting drug absorption,
 distribution, metabolism and excretion (ADME), including but not limited to:
 bariatric procedure, irritable bowel syndrome (IBS), peptic
 ulcer(s),cholecystectomy, and chronic liver disease.

 6. Donated blood or plasma within 8 weeks before the first dose administration to a
 blood bank or blood donation center.

 7. History of drug abuse (as defined by the current version of the Diagnostic and
 Statistical Manual (DSM) within 2 years before dosing, or positive drug screening
 test reflecting consumption of illicit drugs.

 8. History of alcohol abuse (as defined by the current version of the DSM) within 2
 years before dosing, or positive alcohol screen.

 9. Known to have serum hepatitis or known to be a carrier of the hepatitis B surface
 antigen (HBsAg), or hepatitis C antibody, or have a positive result to the test
 for HIV antibodies at Screening.

 10. Exposed to an investigational drug (new chemical entity) within 30 days preceding
 the first dose administration, or 5 half-lives of that investigational drug, if
 known (whichever is longer).

 11. Smokes more than 10 cigarettes, or consumes the equivalent in tobacco, per day.

 12. Subjects who are part of the staff personnel or family members of the
 investigational study staff.

 13. Subjects who, for any reason, are deemed by the investigator to be inappropriate
 for this study, including subjects who are unable to communicate or to cooperate
 with the investigator or the clinical staff.

 -  Exclusion Criteria for Hepatically Impaired Subject (Groups 2, 3 and 4)

 1. Any serious medical condition (excluding hepatic impairment and related
 complications), clinically significant laboratory abnormality not related to
 hepatic impairment and related complications, or psychiatric illness that would
 prevent the subject from signing the ICD and participating in the study.

 2. Any unstable clinically significant illness other than moderate or severe hepatic
 impairment within 3 months prior to the subject signing the ICD.

 3. Hepatic encephalopathy with time-disorientation, somnolent, stuporous, place
 disorientation, hyperactive reflexes, rigidity, slower electroencephalography
 (EEG) waves, unrousable coma, no personality/behavior, decerebrate, and slow 2-3
 counts per second (cps) delta activity.

 4. Have a positive test result for Human Immunodeficiency Virus (HIV) antibodies.

 5. Donated blood or plasma within 8 weeks before the first dose administration to a
 blood bank or blood donation center.

 6. History of drug abuse (as defined by the current version of the Diagnostic and
 Statistical Manual (DSM) within 2 years before dosing, or positive drug screening
 test reflecting consumption of illicit drugs.

 7. Exposed to an investigational drug (new chemical entity) within 30 days preceding
 the first dose administration, or 5 half-lives of that investigational drug, if
 known (whichever is longer).

 8. Smokes more than 10 cigarettes, or consumes the equivalent in tobacco, per day.

 9. Subjects who are part of the staff personnel or family members of the
 investigational study staff.

 10. Subjects who, for any reason, are deemed by the investigator to be inappropriate
 for this study, including subjects who are unable to communicate or to cooperate
 with the investigator or the clinical staff.