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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Renal Insufficiency, Chronic, Hepatic Insufficiency, Healthy

Intervention / Treatment
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* Drug: Sporanox
* Drug: Diclofenac Sodium


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sporanox<br>Active arm approved as an anti-fungal being used to compare HPβCD when administered in DIC075V compared to Sporanox. | Drug: Sporanox<br>* 200 mg<br>|
| Experimental: Dyloject<br>Diclofenac Sodium | Drug: Diclofenac Sodium<br>* 37.5 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Screening - Follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and pharmacokinetics of HPβCD following a single-dose of DIC075V and Sporanox in healthy adult volunteers. |  | Screening - Follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal, Hepatic, Healthy