Study of Intraperitoneal Triferic in Patients on Chronic Peritoneal Dialysis

This is a phase 1, open-label, dose escalation study assessing the pharmacokinetic (PK) profile, maximum concentration (Cmax) and Area Under the Concentration Time Curve (AUC0-t) of Triferic iron administered intraperitoneally in chronic kidney disease patients on peritoneal dialysis (Continuous Cycling Peritoneal Dialysis (CCPD) or Continuous Ambulatory Peritoneal Dialysis (CAPD)).

Screening can be up to 4 weeks, and the enrollment period is approximately one week. There are two treatment (dosing) visits and one follow-up visit during the enrollment period.

At each treatment visit, the patients will be randomly assigned to receive either a single ascending dose of Triferic administered intraperitoneal (IP) during a long (12 hour) peritoneal dialysis dwell or a single 6.6 mg dose of Triferic administered IV over 4 hours. Blood samples will be obtained at defined times over 12 hours to establish the total serum iron PK of IP Triferic as well as the clinical serum iron profile.

The IP dose of the first Cohort will be 5 mg Triferic iron/liter IP. Subsequent Cohort IP doses will be 12.5 mg Triferic iron/liter, and 20 mg Triferic iron/liter, with the final Cohort dose to be determined (TBD). The IV dose will be 6.6. mg for all Cohorts. Six patients will be enrolled in each Cohort, with enrollment in the subsequent (higher dose) Cohort not being initiated until the completion and evaluation of the previous (lower dose) Cohort.

Inclusion criteria

• The patient must be able to provide informed consent and have personally signed and dated the study written informed consent document before completing any study-related procedures.
• The patient must be 18-75 years of age inclusive at the time of consent.
• Have a diagnosis of End Stage Renal Disease and have been on Peritoneal Dialysis for at least 3 months (CAPD or CCPD) prior to Screening.
• Be in a stable clinical condition during the four weeks immediately prior to Screening Period as demonstrated by medical history, physical examination and laboratory testing
• Have a blood hemoglobin concentration above 9.5 g/dL.
• Have a total iron binding capacity (TIBC) of ≥ 175 µg/dL.
• Have not experienced peritonitis episodes in the last 3 months prior to Screening.
• The patient must agree to discontinue all iron preparations for 14 days prior to Study PD #1/Day 1.
• Female patients must be nonpregnant and not breastfeeding. They must either have been amenorrheic for the past year or agree to not become pregnant by continuous use of an effective birth control method acceptable to the Investigator for the duration of their participation in the study.

Exclusion criteria

• The patient has had an red blood cell (RBC) or whole blood transfusion within 4 weeks prior to Screening.
• The patient has had administration of IV or oral iron supplements (including multivitamins with iron) within 14 days prior to Study PD #1/Day 1.
• The patient has known active bleeding from any site (e.g., gastrointestinal, hemorrhoid, nasal, pulmonary, etc.).
• The patient has a living kidney donor identified or living-donor kidney transplant scheduled to occur during study participation. (Note: Patients awaiting deceased-donor transplant need not be excluded.)
• The patient is scheduled to have a surgical procedure during the study.
• The patient has had a hospitalization within the 4 weeks prior to Screening (except for vascular access surgery) that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of the study.
• The patient has a history of noncompliance with the dialysis regimen in the opinion of the Investigator.
• The patient has a known ongoing inflammatory disorder (other than chronic kidney disease), such as systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular disease, that currently requires systemic anti-inflammatory or immunomodulatory therapy.
• The patient has any current febrile illness (e.g., oral temperature ≥100.4°F, 38.0°C). (Patients may subsequently become eligible at least 1 week after resolution of the illness.)
• The patient has known bacterial, tuberculosis, fungal, viral, or parasitic infection requiring anti-microbial therapy or anticipated to require anti-microbial therapy during the patient's participation in this study.
• The patient is known to be positive for HIV, hepatitis B, or hepatitis C (viral testing is not required as part of this protocol).
• The patient has cirrhosis of the liver based on histological criteria or clinical criteria (e.g., presence of ascites, esophageal varices, multiple spider nevi, or history of hepatic encephalopathy).
• The patient has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels consistently greater than twice the upper limit of normal at any time during the two months prior to Study PD #1/Day 1.
• The patient currently has any malignancy other than basal or squamous cell skin cancer.
• The patient has a history of drug or alcohol abuse within the 6 months prior to Screening.
• The patient participated in an investigational drug study within 30 days prior to Study PD #1/Day 1.
• The patient has any condition that, in the opinion of the Investigator, would make it unlikely for the patient to complete the study.