Vitamin D deficiency Nutritional, Metabolic, Endocrine Vitamin D deficiency
Conditions
Interventions
The first screening visit will take place between Day -21 and Day -2. Study participants will be randomly allocated, according to a randomised parallel group design (1:1:1), to one treatment according
Sponsors
IBSA Institut Biochimique (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent before inclusion in the study 2. Aged 40-70 years inclusive 3. Body Mass Index (BMI) 20-29 kg/m² inclusive 4. Systolic blood pressure between 100-139 mmHg, diastolic blood pressure between 50-89 mmHg, heart rate between 50-90 bpm (all measured after 5 min at rest in the sitting position) 5. Ability to comprehend the full nature and purpose of the study, including possible risks and side effects, and to co-operate with the investigator, and to comply with the requirements of the entire study 6. Women of childbearing potential must be using at least one of the following reliable methods of contraception: 6.1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit 6.2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit 6.3. A male sexual partner who agrees to use a male condom with spermicide 6.4. A sterile sexual partner 7. Female participants of non-child-bearing potential or in post-menopausal status for at least one year will be admitted 8. For all women, pregnancy test result must be negative at screening and Day -1
Exclusion criteria
Exclusion criteria: 1. Clinically significant abnormalities on 12-lead (supine position) electrocardiogram (ECG) 2. Clinically significant abnormal physical findings which could interfere with the objectives of the study 3. Clinically significant abnormal laboratory values indicative of physical illness, especially hypercalcemia and hypercalciuria 4. Ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients, history of anaphylaxis to drugs, or history of allergic reactions in general which the investigator considers may affect the outcome of the study 5. Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, or neurological diseases that may interfere with the aim of the study, especially sarcoidosis, kidney failure, nephrolithiasis, nephrocalcinosis, or liver failure 6. Medications including over the counter (OTC) medications, herbal remedies, and supplements, especially those containing calcium, magnesium or vitamin D, for 2 weeks before the start of the study. Hormonal contraceptives and hormonal replacement therapy for women will be allowed. 7. Participation in the evaluation of any investigational product within the 3 months of the first day of this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study. 8. Blood donations within the 3 months of the first day of this study 9. History of drug, alcohol (>1 drink/day for women and >2 drinks/day for men), caffeine (>5 cups/day of coffee or tea) or tobacco abuse (=10 cigarettes/day) 10. Positive result at the drug test at screening or Day -1 11. Positive alcohol breath test at Day -1 12. Abnormal diets (3500 kcal/day), substantial changes in eating habits within 4 weeks of the first day of this study, vegetarian diet; or high vitamin D and calcium dietary intake within 4 weeks of the first day of this study 13. Exposure to strong sunlight or UV sources within 2 weeks of the first day of this study 14. Pregnant or lactating women or a positive or missing pregnancy test at screening or Day -1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Bioavailability of vitamin D3 after a single oral dose of Test (T) or marketed reference (R), under fed conditions, measured as maximum serum concentration (Cmax) and area under the plasma drug concentration-time curve (AUC0-t) of for plasma calcifediol (25(OH)D3) using a fully validated Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method, with a lower quantification limit of 1 ng/ml, on blood samples taken at -12, -1, and 0 h, 15 and 30 min, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 144, 312, 480 and 648 h | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maximum serum concentration (Cmax) and area under the plasma drug concentration-time curve (AUC0-t) of for plasma calcifediol (25(OH)D3) after a single dose administration of T under fasting and fed conditions measured using a fully validated Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method, with a lower quantification limit of 1 ng/ml, on blood samples taken at -12, -1, and 0 h, 15 and 30 min, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 144, 312, 480 and 648 h 2. Pharmacokinetic (PK) profile of 25(OH)D3 after a single dose administration of T and R under fed conditions measured using a fully validated Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method, with a lower quantification limit of 1 ng/ml, on blood samples taken at -12, -1, and 0 h, 15 and 30 min, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 144, 312, 480 and 648 h 3. PK profile of 25(OH)D3 after a single dose administration of T under fasting conditions measured using a fully validated Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method, with a lower quantification limit of 1 ng/ml, on blood samples taken at -12, -1, and 0 h, 15 and 30 min, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 144, 312, 480 and 648 h 4. Safety and tolerability of Vitamin D3 will be evaluated during the study by the number of adverse events (AEs) reported throughout the study duration and measured using: 4.1. Blood and urine samples for haematology, blood chemistry, and urine analysis at the screening visit and final visit/ETV 4.2. Body weight at the screening visit and final visit/ETV and height at the screening visit to calculate Body Mass Index (BMI) at the screening visit and final visit/ETV 4.3. Vital signs (blood pressure [mmHg], heart rate [bpm]) at the screening visit, -1 days, and final visit/ETV 4.4. 12-Lead electrocardiogram at the screening vi | — |
Countries
Italy, Switzerland
Outcome results
None listed