A Clinical Trial of Epizon-701 (EPN-701) in Subjects With End-Stage Renal Disease (ESRD)

Study Overview
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Brief Summary
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Patients with End Stage Renal Disease (ESRD) are prone to early and accelerated vascular calcification. Both the prevalence and extent of the vascular calcification are predictive for cardiovascular morbidity and all-cause mortality in this population. There is a growing body of evidence suggesting that dialysis patients have a primary, functional deficiency of Vitamin K2 as evidenced by reduced levels of circulating biomarkers including carboxylated forms of Matrix Gla Protein (MGP), Osteocalcin, and Fetuin-A, which are important inhibitors of vascular calcification. Decreased levels of Vitamin K2 are known to lead to microvascular calcification and are associated with dermatological and cardiovascular conditions such as calciphylaxis and peripheral arterial disease (PAD). The purpose of this Phase 2 study is to examine the safety and pharmacokinetics of EPN-701 (menaquinone-7; MK-7) and to assess the effects on certain circulating biomarkers when MK-7 is orally administered once daily for 14 days.

Detailed Description
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Patients with End Stage Renal Disease (ESRD) are prone to early and accelerated vascular calcification. Both the prevalence and extent of the vascular calcification are predictive for cardiovascular morbidity and all-cause mortality in this population. There is a growing body of evidence suggesting that dialysis patients have a primary, functional deficiency of Vitamin K2 as evidenced by reduced levels of circulating biomarkers including carboxylated forms of Matrix Gla Protein (MGP), Osteocalcin, and Fetuin-A, which are important inhibitors of vascular calcification. Decreased levels of Vitamin K2 are known to lead to microvascular calcification and are associated with dermatological and cardiovascular conditions such as calciphylaxis and peripheral arterial disease (PAD). The purpose of this Phase 2 study is to examine the safety and pharmacokinetics of EPN-701 (menaquinone-7; MK-7) and to assess the effects on certain circulating biomarkers when MK-7 is orally administered once daily for 14 days.

Official Title
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A Phase 2 Prospective Safety/Tolerability, Pharmacokinetics, Surrogate Biomarkers as Proxies for Efficacy Trial of EPN-701 in Subjects With Stable End Stage Renal Disease (ESRD) Receiving Outpatient Hemodialysis

Conditions
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End-Stage Renal Disease (ESRD)

Intervention / Treatment
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* Drug: EPN-701 (Oral)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consenting subjects. Adult male and female who were diagnosed with stable ESRD. Subjects treated with maintenance hemodialysis at least 3 times a week for at least 3 months prior to the first dose of study drug. Clinically stable. Exclusion Criteria: Solid organ transplant. Malignancy. Severe infection requiring intravenous (IV) antibiotics. Any co-existing disease or condition that could have compromised the safety of study participants and/or the integrity of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPN-701, 10mg orally daily over 14 days<br>Single arm | Drug: EPN-701 (Oral)<br>* MK-7<br>* Other names: menaquinone-7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Frequency of treatment-emergent Adverse Events and treatment-emergent AEs assessed as related to the study drug. | Through study completion; over 14 days treatment and one week follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of EPN-701. | • Maximum plasma concentration of EPN-701 (Cmax) [ng/mL]. | Through study completion; over 14 days treatment and one week follow-up. | 
| Time to maximum plasma concentration of EPN-701. | Time to maximum plasma concentration of EPN-701 (Tmax) (h). | Through study completion; over 14 days treatment and one week follow-up. |