Effect of Renal Impairment on the Pharmacokinetics, and Safety of Megestrol Acetate Concentrated Suspension

Inclusion Criteria:

Healthy Subjects with Normal Renal Function

1. BMI ≥18 kg/m2 and ≤35 kg/m2

2. Females of child-bearing potential must use an adequate and reliable method of
contraception. Postmenopausal females must be postmenopausal ≥1 year and have
elevated serum FSH

3. Able to provide written informed consent

4. Normal renal function, defined as estimated creatinine clearance (CLcr) >80 mL/min at
screening

Subjects with Mild, Moderate, or Severe Renal Impairment or ESRD

Meet inclusion criteria 1 through 3 for healthy subjects and the following criteria:

1. Renal impairment defined as creatinine clearance <80 mL/min as determined using the
Cockroft-Gault formula. Subjects grouped according to degree of renal dysfunction:
mild (CLcr = >50 and ≤80 mL/min), moderate (CLcr = >30 and ≤50 mL/min), or severe
(CLcr = ≤30 mL/min)

2. Renal Impairment subjects must have evidence of stable renal impairment. Defined as
having CLcr values within 25% of each other from 2 separately measured serum
creatinine clearances using the Cockroft-Gault formula

3. ESRD subjects require hemodialysis for at least 3 months

4. Subjects with renal impairment or ESRD may have clinical laboratory test result
deviations that are judged by the Investigator to be consistent with the renal
condition of the subject or of no additional clinical significance for this study

5. Subjects with renal impairment or ESRD, must have stable underlying medical
conditions for at least 90 days prior to the start of study participation

6. Renal impaired subjects may smoke up to 5 cigarettes per day

Exclusion Criteria:

Healthy Subjects with Normal Renal Function

1. Clinically significant (history of or active) cardiac, hepatic, renal, pulmonary,
endocrine, neurological, infectious, gastrointestinal, hematologic, oncologic, or
psychiatric disease that could put the subject at increased risk or could interfere
with the objectives of the study

2. Presence of any screening laboratory values outside the range of normal values and
deemed clinically significant by the Investigator

3. Use of a prescription drug within 14 days of study start, a non-prescription drug
within 7 days of study start, or need of concomitant medication during the study

4. Use of any drugs or herbal products known to inhibit or induce liver enzymes involved
in drug metabolism (CYP P450) within 30 days prior to 1st dose

5. History of allergic reaction or serum sickness to any drug or drug metabolites

6. Whole blood donation within 56 days prior to the first MA-CS dose or plasma donation
within 7 days prior to the first MA-CS dose

7. Positive test for HIV antibody or hepatitis B surface antigen (positive HIV or
hepatitis C antibody for ESRD subjects are acceptable)

8. Presence of drugs of abuse and/or alcohol

9. Participation in another investigational drug study within 30 days prior to the first
MA-CS dose

10. History of recent drug abuse or alcohol addiction during past 2 years

11. Pregnant or breastfeeding

12. Consumption of grapefruit containing foods and beverages within 7 days prior to the
first MA-CS dose

13. History of recurrent thromboembolic events, a thromboembolic event in past three
months, or those still receiving long-term anticoagulation for thromboembolism

Subjects with Mild, Moderate, or Severe Renal Impairment or ESRD

Excluded if subjects meet exclusion criteria 4 through 13 for healthy subjects and the
following criteria:

1. Unstable disease defined as concurrent medical conditions that change significantly
within 90 days

2. Changes in concomitant medications within 14 days prior to first dose administration
or expected changes during study participation

3. Subjects with a renal transplant