End-Stage Renal Disease (ESRD)
Conditions
Brief summary
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
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.
Interventions
DRUGEPN-701 (Oral)
MK-7
Sponsors
Epizon Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Through study completion; over 14 days treatment and one week follow up. | Number of Participants with: Treatment-emergent AEs Treatment-emergent AEs assessed as related to the study drug. Serious Adverse Events Deaths |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations of EPN-701. | Through study completion; over 14 days treatment and one week follow-up. | • Maximum plasma concentration of EPN-701 (Cmax) \[ng/mL\]. |
| Time to Maximum Plasma Concentration of EPN-701. | Through study completion; over 14 days treatment and one week follow-up. | Time to maximum plasma concentration of EPN-701 (Tmax) (h). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 15 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L). | Day 1 to Day 15 | The percent change in circulating biomarker: Undercarboxylated MGP (pmol/L) levels from Day 1 (Baseline) to Day 15 was measured. |
| Mean Measure of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L). | Day 15 | Mean value of circulating biomarker: Undercarboxylated MGP (pmol/L) levels on Day 15 was measured. |
| Change From Baseline to Day 22 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L). | Day 1 to Day 22 | The percent change in circulating biomarker: Undercarboxylated MGP (pmol/L) levels from Day 1 (Baseline) to Day 22 was measured. |
| Mean Value of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L) at Day 22. | Day 22 | The mean value of circulating biomarker: Undercarboxylated MGP (pmol/L) levels on Day 22 was measured. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EPN-701, 10mg Orally Daily Over 14 Days Single arm
EPN-701 (Oral): MK-7
Over 14 days | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | EPN-701, 10mg Orally Daily Over 14 Days |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 54.4 years STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 8 Participants |
| Undercarboxylated Matrix Gla Protein (MGP), (pmol/L). | 1031.66 pmol/L STANDARD_DEVIATION 422.563 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 8 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
Number of Participants with: Treatment-emergent AEs Treatment-emergent AEs assessed as related to the study drug. Serious Adverse Events Deaths
Time frame: Through study completion; over 14 days treatment and one week follow up.
Population: All patients who received at least one dose of EPN-701 was included in the safety evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| EPN-701 Treatment Arm | Number of Participants With Adverse Events (AEs) | 8 participants |
Secondary
Plasma Concentrations of EPN-701.
• Maximum plasma concentration of EPN-701 (Cmax) \[ng/mL\].
Time frame: Through study completion; over 14 days treatment and one week follow-up.
Population: Pharmacokinetic (PK) Population: All enrolled patients who received all 14 days of dosing of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPN-701 Treatment Arm | Plasma Concentrations of EPN-701. | 256 ng/mL | Standard Error 138 |
Secondary
Time to Maximum Plasma Concentration of EPN-701.
Time to maximum plasma concentration of EPN-701 (Tmax) (h).
Time frame: Through study completion; over 14 days treatment and one week follow-up.
Population: All enrolled patients who received all 14 days of dosing of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPN-701 Treatment Arm | Time to Maximum Plasma Concentration of EPN-701. | 5.83 hours | Standard Error 1.66 |
Other Pre-specified
Change From Baseline to Day 15 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L).
The percent change in circulating biomarker: Undercarboxylated MGP (pmol/L) levels from Day 1 (Baseline) to Day 15 was measured.
Time frame: Day 1 to Day 15
Population: Patients who had evaluable biomarker levels at Day 1 and Day 15.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPN-701 Treatment Arm | Change From Baseline to Day 15 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L). | -50.72 percent change | Standard Deviation 20.041 |
Other Pre-specified
Change From Baseline to Day 22 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L).
The percent change in circulating biomarker: Undercarboxylated MGP (pmol/L) levels from Day 1 (Baseline) to Day 22 was measured.
Time frame: Day 1 to Day 22
Population: Patients who had evaluable biomarker levels at Day 1 and Day 22.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPN-701 Treatment Arm | Change From Baseline to Day 22 in Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L). | -48.41 percent change | Standard Deviation 19.994 |
Other Pre-specified
Mean Measure of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L).
Mean value of circulating biomarker: Undercarboxylated MGP (pmol/L) levels on Day 15 was measured.
Time frame: Day 15
Population: Patients who had evaluable biomarker levels at Day 1 and Day 15.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPN-701 Treatment Arm | Mean Measure of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L). | 439.32 pmol/L | Standard Deviation 117.083 |
Other Pre-specified
Mean Value of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L) at Day 22.
The mean value of circulating biomarker: Undercarboxylated MGP (pmol/L) levels on Day 22 was measured.
Time frame: Day 22
Population: Patients who had evaluable biomarker levels at Day 1 and Day 22.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EPN-701 Treatment Arm | Mean Value of Circulating Biomarker: Undercarboxylated Matrix Gla Protein (MGP), (Pmol/L) at Day 22. | 468.80 pmol/L | Standard Deviation 143.733 |