25-Hydroxyvitamin D Pharmacokinetic Study

Study Overview
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Brief Summary
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To evaluate the pharmacokinetic parameters of orally administered 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D3 from the corresponding serum concentration-time curves in healthy adults and adults with a history of intestinal malabsorption.

Detailed Description
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Patients with a history of intestinal malabsorption (n=10) and healthy volunteers (n=10); (of both sexes and all ethnicities) will be recruited in this randomized double-blind crossover study. All subjects will be prescreened for 25(OH)D levels to include subjects with 25(OH)D<30 ng/ml. The subjects will be randomized to receive a single oral dose of 900 µg of either vitamin D3 or 25(OH)D3. Blood samples will be taken at baseline and at 2,4,6,8,12 hours and days 1,2,3, 7 and 14. After a washout period of at least 14 days (2 weeks) the subjects will receive in a double blinded manner a single oral dose of 900 µg of either 25(OH)D3 or vitamin D3 (depending on which one they took in the randomization) any time after the washout. Blood samples will be taken at baseline and at 2,4,6,8,12 hours and days 1,2,3,7, 14. Serum levels of calcium, phosphorus, albumin, creatinine, intact parathyroid hormone (iPTH) will be obtained at baseline and at day 14 (or within a reasonable time if unable to come in on the exact day). Vitamin D and 25(OH)D will be determined on all the blood samples collected at the various times.

Official Title
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Pilot Clinical Trial to Evaluate the Pharmacokinetics of Orally Administered 25-hydroxyvitamin D3 and Vitamin D3 in Healthy Adults and Adults With a History of Intestinal Malabsorption

Conditions
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Vitamin D Deficiency, Fat Malabsorption

Intervention / Treatment
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* Drug: Calcifediol
* Drug: Calciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female with history of intestinal fat-malabsorption with confirmed diagnosis Taking vitamin D (ergocalciferol or cholecalciferol). Subjects taking vitamin D supplement of more than 2000 IUs (50 micrograms)/day) that may interfere with study endpoints must be willing and able to discontinue use of these supplements for the duration of the study and allow for at least a 14-day washout prior to prescreening and enrollment. Women of child bearing potential must be on birth control and not pregnant based on a negative pregnancy test at baseline for each of the 2 pharmacokinetic studies. Serum total 25(OH)D < 30 ng/mL Exclusion Criteria: Unwilling to discontinue use of supplemental dose of vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) daily equivalent (2,000 IU/50 μg) 1 week or less prior to randomization and during the study On medications that can affect vitamin D metabolism including steroids such as prednisone, anti-seizure medications and medications to treat HIV. Tanning in a tanning bed at least one week before the study and throughout the duration of this study. Anyone anticipating going on holiday (where exposure to sun is imminent) 1 week before or during the entire study. Participation in the study or any reason which, in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely History of elevated serum calcium Chronic hepatic or renal failure Subjects with a history of an adverse reaction to orally administered vitamin D. Inability to give informed consent

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each arm will first receive 25(OH)D and then vitamin D or vitamin D and then 25(OH)D
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fat-Mal, calcifediol then calciferol<br>Participants with diagnosed fat malabsorption syndrome will initially receive one capsule of calcifediol for the first round of blood draws and then receive one capsule of calciferol for the second round. | Drug: Calcifediol<br>* One capsule of 900 micrograms of 25(OH)D<br>* Other names: 25(OH)D;Drug: Calciferol<br>* One capsule of 900 micrograms of Vitamin D<br>* Other names: Vitamin D;|
| Experimental: Fat-Mal, calciferol then calcifediol<br>Participants with diagnosed fat malabsorption syndrome will initially receive one capsule of calciferol for the first round of blood draws and then receive one capsule of calcifediol for the second round. | Drug: Calcifediol<br>* One capsule of 900 micrograms of 25(OH)D<br>* Other names: 25(OH)D;Drug: Calciferol<br>* One capsule of 900 micrograms of Vitamin D<br>* Other names: Vitamin D;|
| Experimental: Non Fat-Mal, calcifediol then calciferol<br>Participants that do not have a diagnosed fat malabsorption syndrome will initially receive one capsule of calcifediol for the first round of blood draws and thenreceive one capsule of calciferol for the second round. | Drug: Calcifediol<br>* One capsule of 900 micrograms of 25(OH)D<br>* Other names: 25(OH)D;Drug: Calciferol<br>* One capsule of 900 micrograms of Vitamin D<br>* Other names: Vitamin D;|
| Experimental: Non Fat-Mal, calciferol then calcifediol<br>Participants that do not have a diagnosed fat malabsorption syndrome will initially receive one capsule of calciferol for the first round of blood draws and then receive one capsule of calcifediol for the second round. | Drug: Calcifediol<br>* One capsule of 900 micrograms of 25(OH)D<br>* Other names: 25(OH)D;Drug: Calciferol<br>* One capsule of 900 micrograms of Vitamin D<br>* Other names: Vitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum vitamin D status | The serum vitamin D status (pg/mL) will be determined at multiple time points secondary to receiving a single dose of either calciferol or calcifediol. We will obtain 11 time points after each drug administration which will allow us to observe the fluctuation in vitamin D status after receiving the study drug. | 2 weeks after administration | 
| Change in 25-Hydroxyvitamin D Status | The serum 25(OH)D status (ng/mL) will be determined at multiple time points secondary to receiving a single dose of either calciferol or calcifediol. We will obtain 11 time points after each drug administration which will allow us to observe the fluctuation in 25(OH)D status after receiving the study drug. | 2 weeks after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Calcium Levels | Calcium levels will be drawn at baseline and at the end of each intervention period. This measure will allow us to ensure no change to baseline levels after receiving the study drug. | Baseline and completion of each intervention period (2 weeks) | 
| Serum Phosphorus Levels | Phosphorus levels will be drawn at baseline and at the end of each intervention period. This measure will allow us to ensure no change to baseline levels after receiving the study drug. | Baseline and completion of each intervention period (2 weeks) | 
| Serum Albumin Levels | Albumin levels will be drawn at baseline and at the end of each intervention period. This measure will allow us to ensure no change to baseline levels after receiving the study drug. | Baseline and completion of each intervention period (2 weeks) | 
| Serum Creatinine levels | Creatinine levels will be drawn at baseline and at the end of each intervention period. This measure will allow us to ensure no change to baseline levels after receiving the study drug. | Baseline and completion of each intervention period (2 weeks) | 
| Serum intact parathyroid hormone levels | iPTH levels will be drawn at baseline and at the end of each intervention period. This measure will allow us to ensure no change to baseline levels after receiving the study drug. | Baseline and completion of each intervention period (2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calcifediol (25(OH)D), Calciferol (Vitamin D)