Clinical trial NCT00805090: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency, Chronic
Hepatic Insufficiency
Healthy
Keywords: Renal
Hepatic
Healthy
Lead sponsor: Javelin Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-12-09
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER

Brief summary: 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®.

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.

Eligibility 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).

Primary outcomes:
measure: 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.
timeFrame: Screening - Follow-up
Secondary outcomes:
measure: To evaluate the safety and pharmacokinetics of HPβCD following a single-dose of DIC075V and Sporanox in healthy adult volunteers.
timeFrame: Screening - Follow-up
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: Davita Clinical Research
state: Minnesota
city: Knoxville
country: United States
facility: New Orleans Clinical Center for Research
state: Tennessee
city: Merthyr Tydfil
country: United Kingdom
facility: Simbec Research, Ltd.
Study officials:
affiliation: New Orleans Clinical Center for Research
name: William Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Davita Clinical Research
name: Suzanne Swann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Orlando Clinical Research Center
name: Thomas Marbury, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Simbec Research
name: Salvatore Febbraro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hamilton DA, Ernst CC, Kramer WG, Madden D, Lang E, Liao E, Lacouture PG, Ramaiya A, Carr DB. Pharmacokinetics of Diclofenac and Hydroxypropyl-beta-Cyclodextrin (HPbetaCD) Following Administration of Injectable HPbetaCD-Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment. Clin Pharmacol Drug Dev. 2018 Feb;7(2):110-122. doi: 10.1002/cpdd.417. Epub 2017 Dec 2.