Open-Label, Single-Dose Study to Evaluate the Safety and PK of DIC075V in Subjects With Renal Insufficiency and Hepatic Impairment Compared to Healthy Subjects and Evaluate the Safety and Pharmacokinetics of HPβCD When Administered in DIC075V Compared to Sporanox® in Healthy Subjects

Condition(s) targeted: Renal Insufficiency, Chronic; Hepatic Insufficiency; Healthy

Intervention: Sporanox (Drug); Diclofenac Sodium (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Javelin Pharmaceuticals

Official(s) and/or principal investigator(s):
William Smith, MD, Principal Investigator, Affiliation: New Orleans Clinical Center for Research
Suzanne Swann, MD, Principal Investigator, Affiliation: Davita Clinical Research
Thomas Marbury, MD, Principal Investigator, Affiliation: Orlando Clinical Research Center
Salvatore Febbraro, MD, Principal Investigator, Affiliation: Simbec Research, Ltd.

Overall contact:
Cynthia Ernst, Phone: 617-349 4500, Email: cernst@javelinpharma.com

An open-label, single-dose study to evaluate the safety and pharmacokinetics of DIC075V in subjects with mild or moderate chronic renal insufficiency and in patients with mild chronic hepatic impairment compared. Additionally, the healthy adult volunteers will participate in a randomized, open-label, crossover study in which they will receive Sporanox® to compare the safety and pharmacokinetics of HPβCD when administered in DIC075V compared to Sporanox®.

Official title: An Open-Label, Single-Dose Study to Evaluate the Safety and Pharmacokinetics of DIC075V in Subjects With Mild or Moderate Chronic Renal Insufficiency and in Subjects With Mild Chronic Hepatic Impairment Compared to Healthy Adult Volunteers and a Randomized, Open-Label, Single-Dose, Two-Way, Crossover Study to Evaluate the Safety and Pharmacokinetics of HPβCD When Administered in DIC075V Compared to Sporanox® in Healthy Adult Volunteers.

Study design: Other, Open Label, Active Control, Crossover Assignment, Safety Study

Primary outcome: To evaluate the safety and pharmacokinetics of diclofenac and HPβCD following a single-dose of DIC075V in subjects with mild or moderate chronic renal insufficiency and in subjects with mild hepatic impairment compared to healthy adult volunteers.

Secondary outcome: To evaluate the safety and pharmacokinetics of HPβCD following a single-dose of DIC075V and Sporanox in healthy adult volunteers.

Detailed description: For the renal and hepatic subjects, following the screening visit, eligible subjects will return to the study site on Study Day 0 and remain at the site for 2 nights and 2 days. Study drug administration will occur on Study Day 1. Subjects will be discharged on Study Day 2 after the last blood sample has been collected. Subjects will return 7 ± 3 days after dosing with study drug to have final safety assessments performed. For the healthy subjects, following the screening visit, eligible subjects will return to the study site on Study Day 0 and remain at the site for 3 nights and 3 days. Study drug administration will occur on Study Day 1 and Study Day 2. Subjects will be discharged on Study Day 3 after the last blood sample has been collected. Subjects will return 7 ± 3 days after receiving the last dose of study drug to have final safety assessments performed.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria (General):

- The subjects must be males or females and ≥ 18 years of age and ≤ 65 years.

- The subject must be willing and able to provide signed informed consent.

- The subject must be willing and able to stay at the clinical site for the required

number of days and nights and return to the clinic in 7 ± 3 days after dosing with study drug.

Inclusion Criteria (subjects with mild or moderate chronic renal insufficiency):

- The subject must have mild or moderate chronic renal insufficiency and documented

history of stable renal disease for 1 month prior to screening and clinical laboratory test results consistent with the underlying disease for renal impairment.

Inclusion Criteria (subjects with mild chronic hepatic impairment):

- The subject must have mild chronic hepatic impairment, as defined by Child-Pugh

Classification A, Score of 5-6 and a bilirubin of ≤ 2. 5 mg/dl.

Inclusion Criteria (for healthy subjects):

- Healthy subjects will be matched to renally impaired subjects in this study by age (+

10 years), gender, and body weight (± 10 kg).

Exclusion Criteria:

- The subject has a known allergy or hypersensitivity to diclofenac, other NSAIDs, any

of the excipients of the study preparation (hydroxypropyl-ß-cyclodextrin (HPßCD), monothioglycerol, sodium hydroxide, hydrochloric acid, and water for injection), itraconzaole or other "azole" drugs, or to any of the excipients in Sporanox (HPßCD, propylene glycol, sodium hydroxide, hydrochloric acid, or water for injection).

Cynthia Ernst, Phone: 617-349 4500, Email: cernst@javelinpharma.com

Simbec Research, Ltd., Merthyr Tydfil CF48 4DR, United Kingdom; Recruiting
Salvatore Febbraro, MD, Principal Investigator

Orlando Clinical Research Center, Orlando, Florida 32809, United States; Recruiting
Thomas C Marbury, MD, Principal Investigator

Davita Clinical Research, Minneapolis, Minnesota 55404, United States; Recruiting
Suzanne Swan, MD, Principal Investigator

New Orleans Clinical Center for Research, Knoxville, Tennessee 37920, United States; Recruiting
William Smith, MD, Principal Investigator

Starting date: December 2008
Ending date: April 2009
Last updated: February 10, 2009