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

This study has been terminated.
(Difficulty finding the required subject population)
Sponsor:
Collaborators:
Covance
SFBC Anapharm
Information provided by:
Par Pharmaceutical, Inc.
ClinicalTrials.gov Identifier:
NCT00637403
First received: March 11, 2008
Last updated: March 17, 2008
Last verified: March 2008
  Purpose

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 Intervention Phase
Healthy
Drug: Megestrol acetate concentrated suspension 125 mg/mL
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Par Pharmaceutical, Inc.:

Primary Outcome Measures:
  • Pharmacokinetic blood samples [ Time Frame: predose and serially through 264 hours post dose ] [ Designated as safety issue: No ]
  • Urine collection [ Time Frame: Predose and serially through 264 hours post dose ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: May 2006
Study Completion Date: May 2006
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Megace ES

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00637403

Locations
United States, Florida
SFBC International
Miami, Florida, United States, 33181
Sponsors and Collaborators
Par Pharmaceutical, Inc.
Covance
SFBC Anapharm
Investigators
Principal Investigator: Kenneth C Lasseter, MD SFBC International
Study Director: Lynn D. Kramer, MD Par Pharmaceutical, Inc.
  More Information

No publications provided

Responsible Party: VP Clinical & Medical Affairs, Par Pharmaceutical, Inc
ClinicalTrials.gov Identifier: NCT00637403     History of Changes
Other Study ID Numbers: 100.2.C.002
Study First Received: March 11, 2008
Last Updated: March 17, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Par Pharmaceutical, Inc.:
renal impairment
end stage renal disease
megestrol acetate
pharmacokinetics
hemodialysis
renal dialysis
kidney failure, chronic
renal insufficiency
Megace ES

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Megestrol
Megestrol Acetate
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Appetite Stimulants
Central Nervous System Stimulants
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014