Human Pharmacology Trial of Calcium-vitamin D3 Tablet in Healthy Participants
Condition: Calcium Deficiency; Vitamin D Deficiency
MeSH terms: Vitamin D Deficiency
Intervention: Calcium 500 mg and Vitamin D3 800 IU; Low calcium meals
Intervention description: Calcium 500 mg and Vitamin D3 800 IU chewable tablets; A normal Western European diet with reduced calcium content (400 mg per day).
Intervention MeSH terms: Calcium, Dietary; Vitamin D; Cholecalciferol; Calcium
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 45 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy; Increase in calcium urinary excretion and PTH decrease in serum

Summary:

      The purpose of this study is to demonstrate that the intestinal absorption of calcium from a
      newly developed calcium carbonate-vitamin D3 chewable tablet formulation increases the amount
      of calcium excreted in urine and decreases parathyroid hormone (PTH) in serum as compared to
      baseline.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is a healthy postmenopausal woman (last menses at least 2 years before signing
             informed consent and follicle stimulating hormone (FSH) confirming postmenopausal
             status) or a healthy male aged between 45 to 70 years inclusively

          2. Was informed both verbally and in writing about the objectives of the clinical trial,
             the methods, the anticipated benefits and potential risks and the discomfort to which
             she/he might be exposed, and had given written consent to participation in the trial
             prior to any trial-related procedure

          3. Is Caucasian

          4. Is assessed as healthy based on physical examination, medical history, clinical
             laboratory, electrocardiogram (ECG), vital signs

          5. Is a non-smoker (having abstained from smoking for at least 6 months)

          6. Has a body mass index of 19 to 29.4 kg/m^2 (inclusively)

        Exclusion Criteria:

          1. Has a history of clinically significant allergies or idiosyncrasies to calcium or
             vitamin D3, or any inactive ingredient(s) of these products

          2. Is a lactating or pregnant female participant

          3. Female participants: Has a positive pregnancy test in serum at screening and in urine
             on Day -1 Period 1

          4. Participant was previously enrolled into the current clinical trial

          5. Has participated in the active treatment phase of another clinical trial where a
             persisting pharmacodynamic (PD) effect of the IMP of that clinical trial cannot be
             excluded (e.g. patient is well into a treatment free safety follow-up phase); or 10
             times the pharmacokinetic (PK) half-life, whatever is longer but 30 days as minimum
             prior to the start of the clinical trial

          6. Has been considered unable or unwilling to co-operate adequately, i.e. to follow
             clinical trial procedures and Investigator instructions adequately (e.g. language
             difficulties, etc.) or participant is anticipated not to be available for scheduled
             clinical trial visits/procedures

          7. Has a dependency situation (e.g. person is kept in detention, Investigator in the
             current clinical trial, or a first-degree relative of a clinical trial Investigator,
             or is employee at the clinical trial site)

          8. Has a hypersensitivity to soya or peanut

          9. Abuse of alcohol or drugs

         10. Has consumed ethanol within 48 hours prior to hospitalization verified by alcohol
             breath test (Alcotest®)

         11. Has a history or current disease which might influence the trial objectives (e.g.,
             urinary tract infection, urination problems [e.g., prostate hyperplasia] or urinary
             incontinence, renal insufficiency, nephrolithiasis, sarcoidosis, osteoporosis, calcium
             deficiency, hyper- or hypoparathyroidism, hypercalciuria, hypercalcaemia, calcium
             lithiasis, hyperphosphataemia, hypervitaminosis D, phenylketonuria, diabetes mellitus

         12. Has creatinine clearance according to Modification of Diet in Renal Disease (MDRD)
             equation of < 60 mL/min

         13. Has regular use of any medication. Treatment with biphosphonates in the past 5 years,
             amidorone in the past 6 months, calcium or fluoride supplements, diuretics, vitamin D
             preparations, estrogens or estrogen receptor modulators, enzyme inducing agents,
             teriparatide or parathyroid hormone (PTH(1-84)), bile sequestrants within 3 months
             before screening, and for all other drugs within 2 weeks before screening (or 6 times
             the half-life of the respective drug) whatever is longer

         14. Has use of ultraviolet radiation cabins or sunbath longer than 1 h from 1 week before
             Day 1 of Period 1 until the End of Trial examination

         15. Has an intake of milk and milk products, broccoli, dark-green vegetables, vegetables
             from the mustard green family, fatty fish, eggs, liver, and added salt within 7 days
             prior to hospitalisation

         16. Has unusual diet habits and practicing vegetarians

         17. Has beverages and food containing poppy seed (i.e. poppy seed rolls, poppy seed cake,
             milk shakes containing poppy seed) from 72 hours before drug screen to avoid
             interference

         18. Has chinine, grapefruit- and star fruit-containing beverages and food, St. John's wort
             (known Cytochrome P450 (CYP450) inhibitors and inducers) within 7 days prior to
             hospitalization

         19. Has excessive consumption of caffeinated beverages (more than five cups of coffee or
             equivalent per day)

         20. Has consumption of xanthine-containing beverages and food (e.g. coffee, black and
             green tea, cola, chocolate) 48 hours prior to hospitalization

         21. Has evidence of acute or chronic hepatitis B or C. Positive test for hepatitis B
             surface antigen (HBsAg), antibody to the hepatitis B core antigen (anti-HBc) or
             antibody to the hepatitis C virus (anti-HCV antibody), or human immunodeficiency virus
             (HIV) infection at screening

         22. Has history of gastrointestinal surgery (except appendectomy) or any other
             gastrointestinal condition or disease that might influence (calcium) absorption

         23. Has any condition, including laboratory findings or findings in the medical history or
             screening assessments that, in the opinion of the Investigator, constitutes a specific
             risk or a contraindication for the participant's participation in the trial or that
             could interfere with the trial objectives, conduct or evaluation

         24. Has any comedication required during the trial.