Human Pharmacology Trial of Calcium-vitamin D3 Tablet in Healthy Participants

Study Overview
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Brief Summary
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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.

Detailed Description
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The drug being tested in this study is called Calcichew. This study will look at calcium absorption in healthy postmenopausal women and healthy men. The study will enroll approximately 55 healthy adults. All participants will receive Calcichew. All participants will be asked to take one chewable tablet at the same time each day for three days in period 2 of the trial. This trial will be conducted at one clinical site in Germany. The overall time to participate in this study is 4 weeks. Participants will make 9 visits to the clinic, and will be contacted by telephone 7days after last dose of study drug for a follow-up assessment.

Official Title
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A Two Period, One-sequence Open-label Study of a Newly Developed Calcium Carbonate-vitamin D3 Chewable Tablet Formulation (Calcium 500 mg and Vitamin D3 800) Dosed for Three Days to Investigate the Effect on Urine Calcium and Serum Parathyroid Hormone (PTH) as Measurements of Intestinal Calcium Absorption in Healthy Postmenopausal Women and Healthy Men Compared to Baseline.

Conditions
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Calcium Deficiency, Vitamin D Deficiency

Intervention / Treatment
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* Drug: Calcium 500 mg and Vitamin D3 800 IU
* Other: Low calcium meals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 Is Caucasian Is assessed as healthy based on physical examination, medical history, clinical laboratory, electrocardiogram (ECG), vital signs Is a non-smoker (having abstained from smoking for at least 6 months) Has a body mass index of 19 to 29.4 kg/m^2 (inclusively) Exclusion Criteria: Has a history of clinically significant allergies or idiosyncrasies to calcium or vitamin D3, or any inactive ingredient(s) of these products Is a lactating or pregnant female participant Female participants: Has a positive pregnancy test in serum at screening and in urine on Day -1 Period 1 Participant was previously enrolled into the current clinical trial 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 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 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) Has a hypersensitivity to soya or peanut Abuse of alcohol or drugs Has consumed ethanol within 48 hours prior to hospitalization verified by alcohol breath test (Alcotest®) 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 Has creatinine clearance according to Modification of Diet in Renal Disease (MDRD) equation of < 60 mL/min 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 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 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 Has unusual diet habits and practicing vegetarians 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 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 Has excessive consumption of caffeinated beverages (more than five cups of coffee or equivalent per day) Has consumption of xanthine-containing beverages and food (e.g. coffee, black and green tea, cola, chocolate) 48 hours prior to hospitalization 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 Has history of gastrointestinal surgery (except appendectomy) or any other gastrointestinal condition or disease that might influence (calcium) absorption 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 Has any comedication required during the trial.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Calcium 500 mg and Vitamin D3 800 IU<br>Period 1: Low calcium meals for up to 3 days. Period 2: Calcium 500 mg and Vitamin D3 800 IU chewable tablets, orally, once daily for up to 3 days with low calcium meals. | Drug: Calcium 500 mg and Vitamin D3 800 IU<br>* Calcium 500 mg and Vitamin D3 800 IU chewable tablets<br>* Other names: Calcichew-D3 forte 500 mg/800 IU;Other: Low calcium meals<br>* A normal Western European diet with reduced calcium content (400 mg per day).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Calcium Excreted in Urine From 0 Hours up to 6 Hours Post Dose (Ca2+ Ae0-6h) | Ca2+ Ae0-6h was calculated as the urine volume of the urine collected from 0 to 6 hours multiplied by the calcium concentration measured in urine. | Day 3 of Period 1 (Reference) and Day 3 in Period 2. Samples were taken 0-6 Hours post dose | 
| Area Under the Curve From 0 to 6 Hours Post Dose of Parathyroid Hormone (PTH AUC0-6h) in Serum | The area under the curve from 0 to 6 hours post dose of parathyroid hormone (PTH AUC0-6h) in serum, calculated using the linear trapezoidal formula. | Day 3 in Period 1 (Reference) and Day 3 in Period 2. Samples were taken at predose, 0.5, 1, 2, 3, 4, and 6 hour post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Calcium Excreted in Urine From 0 to 6 Hours Post Dose Corected for Creatinine (Ae0-6h/Creatinine) | To account for potential inaccuracies in urine collection, creatinine correction of calcium excretion was also assessed. Ca2+ Ae0-6h/Creatinine was obtained by dividing the urinary concentration of calcium by the urinary creatinine concentration. | Day 3 of Period 1 (Baseline) and Day 3 in Period 2. Samples will be taken 0-6 Hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy, Increase in calcium urinary excretion and PTH decrease in serum