Clinical trial NCT00637403: Effect of Renal Impairment on the Pharmacokinetics, and Safety of Megestrol Acetate Concentrated Suspension
Official title: An Open-Label, Single-Dose Study to Assess the Effect of Renal Impairment on the Pharmacokinetic Characteristics, Safety, and Tolerability of Megestrol Acetate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Keywords: renal impairment
end stage renal disease
megestrol acetate
pharmacokinetics
hemodialysis
renal dialysis
kidney failure, chronic
renal insufficiency
Megace ES
Lead sponsor: Par Pharmaceutical, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Covance
name: SFBC Anapharm
First posted: 2008-03-18
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: To determine the pharmacokinetics and safety of megestrol acetate after a single oral 300 mg dose of megestrol acetate concentrated suspension in healthy subjects, and subjects with varying degrees of renal impairment


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic blood samples
timeFrame: predose and serially through 264 hours post dose
measure: Urine collection
timeFrame: Predose and serially through 264 hours post dose
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: SFBC International
state: Florida
Study officials:
affiliation: SFBC International
name: Kenneth C Lasseter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Par Pharmaceutical, Inc.
name: Lynn D. Kramer, MD
role: STUDY_DIRECTOR
References: