Trial Outcomes & Findings for Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation (NCT NCT03576716)

NCT ID: NCT03576716

Last Updated: 2022-05-17

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. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 19 participants
• Primary outcome timeframe: Baseline, 6 months
• Results posted on: 2022-05-17

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 (\<60 ml/min per 1.73 m2)
Overall Study STARTED	10	9
Overall Study COMPLETED	10	8
Overall Study NOT COMPLETED	0	1

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 (\<60 ml/min per 1.73 m2)
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

Baseline characteristics by cohort

Measure	Healthy Controls n=10 Participants Healthy Controls (n = 10)	CKD Group n=8 Participants CKD Group (n = 8)	Total n=18 Participants Total of all reporting groups
Age, Continuous	60 years STANDARD_DEVIATION 6 • n=5 Participants	69 years STANDARD_DEVIATION 7 • n=7 Participants	64 years STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Clearance after supplement	436 ml/d STANDARD_DEVIATION 135 • n=5 Participants	322 ml/d STANDARD_DEVIATION 88 • n=7 Participants	385 ml/d STANDARD_DEVIATION 128 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

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. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in Metabolic Clearance of D6-25(OH)D3	21 ml/d Interval -63.0 to 105.0	5 ml/d Interval -45.0 to 55.0

SECONDARY outcome

Timeframe: Baseline, 6 months

AUC is calculated using the linear trapezoidal method. Change in the AUC of D6-25(OH)D3 will be calculated as D6-25(OH)D3 AUC measured during CLEAR-PLUS minus D6-25(OH)D3 AUC previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in AUC of D6-25(OH)D3	0.07 ng x day/mL Standard Deviation 11.2	-2.58 ng x day/mL Standard Deviation 7.51

SECONDARY outcome

Timeframe: Baseline, 6 months

Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations. Change in the terminal half-life of D6-25(OH)D3 will be calculated as D6-25(OH)D3 half-life measured during CLEAR-PLUS minus D6-25(OH)D3 half-life previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in Terminal Half-life of D6-25(OH)D3	-1.3 d Interval -6.3 to 3.8	1.2 d Interval -5.1 to 7.4

SECONDARY outcome

Timeframe: Baseline, 6 months

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. Change in the volume of distribution of D6-25(OH)D3 will be calculated as D6-25(OH)D3 volume of distribution measured during CLEAR-PLUS minus D6-25(OH)D3 volume of distribution previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=18 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in Volume of Distribution of D6-25(OH)D3	0.28 L Standard Deviation 4.13	0.55 L Standard Deviation 0.94

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 6 months

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. Changes in the metabolic formation clearance of D6-25(OH)D3 metabolites will be calculated as metabolic formation clearance measured during CLEAR-PLUS minus metabolic formation clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Changes in Metabolic Formation Clearance of D6-25(OH)D3 Metabolites.	0.01 ratio Interval -0.03 to 0.05	-0.02 ratio Interval -0.04 to 0.002

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 7 days

Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3 administration. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in the Serum Concentration of Calcium	0.20 mg/dl Standard Deviation 0.20	0.28 mg/dl Standard Deviation 0.33

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. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in the Serum Concentration of Creatinine	0.03 mg/dl Standard Deviation 0.10	-0.02 mg/dl Standard Deviation 0.15

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. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in the Serum Concentration of AST	1.30 units/L Standard Deviation 4.60	-0.13 units/L Standard Deviation 1.36

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. The change listed is between two timepoints.

Outcome measures

Measure	Healthy Controls n=10 Participants Healthy controls defined as normal eGFR (\>60 ml/min per 1.73m2)	CKD Group n=8 Participants CKD group defined as those with eGFR (\<60ml/min per 1.73m2)
Change in the Serum Concentration of ALT	1.56 units/L Standard Deviation 2.83	0.50 units/L Standard Deviation 2.98

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Participants n=18 participants at risk All Participants (N = 18). AEs were not collected by arm but altogether.
General disorders Sensation in arm during infusion	27.8% 5/18 • 8 weeks Everyone had the same treatment, so it's most appropriate to summarize AEs for the whole group.
Infections and infestations Diverticulitis	5.6% 1/18 • 8 weeks Everyone had the same treatment, so it's most appropriate to summarize AEs for the whole group.

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