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

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.

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®.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; Healthy; Renal Insufficiency, Chronic
• Intervention / Treatment: Drug: Sporanox; Drug: Diclofenac Sodium

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merthyr Tydfil, United Kingdom, CF48 4DR
    • Simbec Research, Ltd.
• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • DaVita Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Clinical Center for Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Sporanox; Active arm approved as an anti-fungal being used to compare HPβCD when administered in DIC075V compared to Sporanox.	Drug: Sporanox; 200 mg
EXPERIMENTAL: Dyloject; Diclofenac Sodium	Drug: Diclofenac Sodium; 37.5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Javelin Pharmaceuticals
• Investigators: Principal Investigator: William Smith, MD, New Orleans Clinical Center for Research; Principal Investigator: Suzanne Swann, MD, DaVita Clinical Research

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): April 1, 2009

Study Registration Dates

• First Submitted: December 8, 2008
• First Submitted That Met QC Criteria: December 8, 2008
• First Posted (ESTIMATE): December 9, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 30, 2009
• Last Update Submitted That Met QC Criteria: April 29, 2009
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: Healthy; Hepatic; Renal
• Additional Relevant MeSH Terms: Digestive System Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Renal Insufficiency, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Diclofenac; Itraconazole
• Other Study ID Numbers: DFC-PK-009