Trial Outcomes & Findings for Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease (NCT NCT02937350)

NCT ID: NCT02937350

Last Updated: 2021-09-01

Results Overview

Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 88 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2021-09-01

Participant Flow

Participant milestones

Measure	Healthy Controls Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group Kidney failure group defined as those with ESKD treated with dialysis
Overall Study STARTED	43	25	20
Overall Study COMPLETED	43	24	20
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Measure	Healthy Controls Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group Kidney failure group defined as those with ESKD treated with dialysis
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

Baseline characteristics by cohort

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis	Total n=87 Participants Total of all reporting groups
Age, Continuous	64 years STANDARD_DEVIATION 10 • n=93 Participants	67 years STANDARD_DEVIATION 11 • n=4 Participants	58 years STANDARD_DEVIATION 9 • n=27 Participants	64 years STANDARD_DEVIATION 11 • n=483 Participants
Sex: Female, Male Female	24 Participants n=93 Participants	8 Participants n=4 Participants	4 Participants n=27 Participants	36 Participants n=483 Participants
Sex: Female, Male Male	19 Participants n=93 Participants	16 Participants n=4 Participants	16 Participants n=27 Participants	51 Participants n=483 Participants
Race (NIH/OMB) Race · American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Race · Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Race · Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Race · Black or African American	12 Participants n=93 Participants	8 Participants n=4 Participants	6 Participants n=27 Participants	26 Participants n=483 Participants
Race (NIH/OMB) Race · White	31 Participants n=93 Participants	16 Participants n=4 Participants	14 Participants n=27 Participants	61 Participants n=483 Participants
Race (NIH/OMB) Race · More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Race · Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Vitamin-D3 Supplement Use	6 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	8 participants n=483 Participants

PRIMARY outcome

Timeframe: 8 weeks

Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Metabolic Clearance of D6-25(OH)D3	360 milliliter per day (ml/d) Standard Deviation 108	313 milliliter per day (ml/d) Standard Deviation 86	263 milliliter per day (ml/d) Standard Deviation 163

SECONDARY outcome

Timeframe: 8 weeks

AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
AUC of D6-25(OH)D3	59.8 nanograms x day/mL (ngxd/mL) Standard Deviation 10.2	68.7 nanograms x day/mL (ngxd/mL) Standard Deviation 10.2	76.6 nanograms x day/mL (ngxd/mL) Standard Deviation 12.0

SECONDARY outcome

Timeframe: 8 weeks

Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Terminal Half-life of D6-25(OH)D3	21.9 days (d) Standard Deviation 5.7	25.5 days (d) Standard Deviation 6.5	35.6 days (d) Standard Deviation 8.1

SECONDARY outcome

Timeframe: 8 weeks

Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Volume of Distribution of D6-25(OH)D3	11.0 Liters (L) Standard Deviation 2.9	11.1 Liters (L) Standard Deviation 2.8	12.5 Liters (L) Standard Deviation 4.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 weeks

Metabolic formation clearance is calculated as the daughter metabolite plasma AUC divided by the AUC of D6-25(OH)D3 (metabolite/parent AUC ratio). AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Metabolic Formation Clearance of D6-25(OH)D3 Metabolites.	0.12 ratio Standard Deviation 0.04	0.08 ratio Standard Deviation 0.03	0.03 ratio Standard Deviation 0.03

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days

Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3 administration

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Change in the Serum Concentration of Calcium	0.42 milligrams/deciliter (mg/dl) Standard Deviation 1.75	0.16 milligrams/deciliter (mg/dl) Standard Deviation 0.26	-0.27 milligrams/deciliter (mg/dl) Standard Deviation 0.48

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 7 days

Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3 administration

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Change in the Serum Concentration of Creatinine	0.04 milligrams/deciliter (mg/dl) Standard Deviation 0.09	-0.05 milligrams/deciliter (mg/dl) Standard Deviation 0.27	2.81 milligrams/deciliter (mg/dl) Standard Deviation 2.26

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 7 days

Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3 administration

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Change in the Serum Concentration of AST	0.40 units/Liter (u/L) Standard Deviation 3.43	0.57 units/Liter (u/L) Standard Deviation 5.98	0.10 units/Liter (u/L) Standard Deviation 5.22

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 7 days

Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3 administration

Outcome measures

Measure	Healthy Controls n=43 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=24 Participants CKD group defined as those with eGFR \<60ml/min per 1.73 m2)	Kidney Failure Group n=20 Participants Kidney failure group defined as those with ESKD treated with dialysis
Change in the Serum Concentration of ALT	0.16 units/Liter (u/L) Standard Deviation 3.71	1.52 units/Liter (u/L) Standard Deviation 6.92	0.45 units/Liter (u/L) Standard Deviation 3.66

Adverse Events

All Participants

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Participants n=87 participants at risk All participants (N=87)
Blood and lymphatic system disorders Deep vein thrombosis	1.1% 1/87 • 8 weeks Everyone had the same treatment, so it was more appropriate to summarize AEs for the whole group. Adverse events were not collected separately per arm.

Other adverse events

Measure	All Participants n=87 participants at risk All participants (N=87)
General disorders Pain or sensation in arm during infusion	18.4% 16/87 • 8 weeks Everyone had the same treatment, so it was more appropriate to summarize AEs for the whole group. Adverse events were not collected separately per arm.

Additional Information

Dr. Ian de Boer

University of Washington

Phone: 206-616-5403

Email: IDeBoer@Nephrology.washington.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place