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

Sponsor

Par Pharmaceutical, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00637403

Collaborator

Covance (Industry), SFBC Anapharm (Industry)

Enrollment

Location

Arms

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Megestrol acetate concentrated suspension 125 mg/mL Drug: Megestrol acetate concentrated suspension 125 mg/mL Drug: Megestrol acetate concentrated suspension 125 mg/mL Drug: Megestrol acetate concentrated suspension 125 mg/mL Drug: Megestrol acetate concentrated suspension 125 mg/mL	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

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 Start Date :

May 1, 2006

Actual Primary Completion Date :

May 1, 2006

Actual Study Completion Date :

May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: I Megestrol acetate concentrated suspension in subjects with normal renal function	Drug: Megestrol acetate concentrated suspension 125 mg/mL Megestrol acetate concentrated suspension (125 mg/mL) administered orally for a total dose of 300 mg (2.4 mL x 125 mg/mL) in subjects with normal renal function (CLcr >80 mL/min) Other Names: Megace ES
Experimental: II Megestrol acetate concentrated suspension in subjects with mild renal impairment	Drug: Megestrol acetate concentrated suspension 125 mg/mL Megestrol acetate concentrated suspension (125 mg/mL) administered orally for a total dose of 300 mg (2.4 mL x 125 mg/mL) in subjects with mild renal impairment (CLcr 50 - 80 mL/min) Other Names: Megace ES
Experimental: III Megestrol acetate concentrated suspension in subjects with moderate renal impairment	Drug: Megestrol acetate concentrated suspension 125 mg/mL Megestrol acetate concentrated suspension (125 mg/mL) administered orally for a total dose of 300 mg (2.4 mL x 125 mg/mL) in subjects with moderate renal impairment (CLcr 30 - <50 mL/min) Other Names: Megace ES
Experimental: IV Megestrol acetate concentrated suspension in subjects with severe renal impairment	Drug: Megestrol acetate concentrated suspension 125 mg/mL Megestrol acetate concentrated suspension (125 mg/mL) administered orally for a total dose of 300 mg (2.4 mL x 125 mg/mL) in subjects with severe renal impairment (CLcr <30 mL/min and not on hemodialysis) Other Names: Megace ES
Experimental: V Megestrol acetate concentrated suspension in subjects with end stage renal disease	Drug: Megestrol acetate concentrated suspension 125 mg/mL Megestrol acetate concentrated suspension (125 mg/mL) administered orally as 2 single doses of 300 mg (2.4 mL x 125 mg/mL) each in subjects with end stage renal disease undergoing hemodialysis. Washout period of 21 days between each dose Other Names: Megace ES

Outcome Measures

Primary Outcome Measures

Pharmacokinetic blood samples [predose and serially through 264 hours post dose]
Urine collection [Predose and serially through 264 hours post dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy Subjects with Normal Renal Function

BMI ≥18 kg/m2 and ≤35 kg/m2
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
Able to provide written informed consent
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:

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)

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
ESRD subjects require hemodialysis for at least 3 months
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
Subjects with renal impairment or ESRD, must have stable underlying medical conditions for at least 90 days prior to the start of study participation
Renal impaired subjects may smoke up to 5 cigarettes per day

Exclusion Criteria:

Healthy Subjects with Normal Renal Function

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
Presence of any screening laboratory values outside the range of normal values and deemed clinically significant by the Investigator
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
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
History of allergic reaction or serum sickness to any drug or drug metabolites
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
Positive test for HIV antibody or hepatitis B surface antigen (positive HIV or hepatitis C antibody for ESRD subjects are acceptable)
Presence of drugs of abuse and/or alcohol
Participation in another investigational drug study within 30 days prior to the first MA-CS dose
History of recent drug abuse or alcohol addiction during past 2 years
Pregnant or breastfeeding
Consumption of grapefruit containing foods and beverages within 7 days prior to the first MA-CS dose
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:

Unstable disease defined as concurrent medical conditions that change significantly within 90 days
Changes in concomitant medications within 14 days prior to first dose administration or expected changes during study participation
Subjects with a renal transplant