Effect of Calcium 500 mg and Vitamin D3 1000 IU Chewable Tablet on Intestinal Calcium Absorption

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Calcichew D3; Drug: Noncarbonated Water

• Registration Number: NCT02338713
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to demonstrate that the intestinal absorption of calcium from a novel calcium carbonate-vitamin D3 chewable tablet formulation (calcium 500 milligrams (mg) and vitamin D3 1000 International Units (IU)) increases the amount of calcium excreted in urine and decreases parathyroid hormone (PTH) in serum as compared with Baseline.

Detailed Description

The drug being tested in this study was called Calcichew D3. Calcichew D3 was being tested to assess how it is processed by the body in healthy men and postmenopausal women. This study looked at lab results in people who take Calcichew D3.

The study enrolled approximately 27 participants. All participants received the same treatment:

• Calcichew D3 (calcium 500 mg and vitamin D3 1000 IU) chewable tablets All participants were asked to take one tablet each morning of the treatment period.

This single-centre trial was conducted in France. The overall time to participate in this study was up to 44 days. Participants made 2 visits to the clinic, including one 7-day period of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Study Timeline

• Study First Submitted: 2014-12-18
• Study Start: 2015-01
• Study First Submitted QC: 2015-01-09
• Study First Posted: 2015-01-14
• Primary Completion: 2015-02
• Study Completion: 2015-02
• Results First Submitted: 2016-03-08
• Status Verified: 2017-04
• Results First Submitted QC: 2017-04-03
• Last Update Submitted: 2017-04-03
• Results First Posted: 2017-06-16
• Last Update Posted: 2017-06-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.
3. Is a healthy adult male or female participant.
4. Female participants should be postmenopausal (last menses at least 2 years before signing informed consent and follicle-stimulating hormone (FSH) confirming postmenopausal status).
5. The participant is White.
6. Is aged 45 to 70 years, inclusive, at the time of informed consent and study enrollment.
7. Weighs at least 50 kg and has a body mass index (BMI) from 18 to 30 kilogram per square meter (kg/m^2), inclusive at Screening and Day -1.
8. Is a nonsmoker (having abstained from smoking for at least 6 months).

Exclusion Criteria

1. Has received any investigational compound within 30 days prior to Screening.
2. Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
3. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
4. Has a known hypersensitivity to calcium or vitamin D3 or to any of the excipients of the formulation of the Calcichew D3 chewable tablet.
5. Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1).
6. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular consumption of 5 or more units per day) within 5 years prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine. Ethanol consumption within 72 hours prior to Check-in (Day -1) verified by alcohol breath test (Alcotest).
7. Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table.
8. Has current or recent (within 6 months) gastrointestinal disorder or gastrointestinal surgery (except appendectomy) that would be expected to influence the absorption of drugs and calcium (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention [eg, cholecystectomy]).
9. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
10. Has a positive test result for hepatitis B surface antigen (HBsAg), antibody to hepatitis C virus (anti-HCV), and human immunodeficiency virus (HIV) antibody at Screening.
11. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 21 days prior to Check-in (Day -1). Cotinine test is positive at Screening or Check-in (Day -1).
12. Has poor peripheral venous access.
13. Has donated or lost 450 millileters (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1.
14. Has a Screening or Check-in (Day -1) abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by both the principal investigator and the Takeda medical monitor.
15. Has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than (>)2.0 times the upper limit of normal (ULN).
16. Is a practicing vegetarian or vegan.
17. Has a creatinine clearance according to Modification of Diet in Renal Disease equation of less than (<)60 mL/min at Screening or Check-in (Day -1).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Noncarbonated Water + Calcichew D3	Calcichew D3	Noncarbonated water 200 milliliter (mL), orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period) followed by Calcichew D3 500 milligram (mg)/1000 international units (IU) (Calcium 500 mg, chewable tablets and vitamin D3 1000 IU, chewable tablets), orally, once daily on Days 4, 5 and 6 in period 2 (study treatment period) of 6 days treatment period.
Noncarbonated Water + Calcichew D3	Noncarbonated Water	Noncarbonated water 200 milliliter (mL), orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period) followed by Calcichew D3 500 milligram (mg)/1000 international units (IU) (Calcium 500 mg, chewable tablets and vitamin D3 1000 IU, chewable tablets), orally, once daily on Days 4, 5 and 6 in period 2 (study treatment period) of 6 days treatment period.

Primary Outcome Measures

Name	Time	Method
PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone	Days 3 and 6: pre-dose and at multiple time-points (upto 6 hours) postdose. Day 3 for the noncarbonated water reporting group and Day 6 for the Calcichew D3 reporting group	The PTH AUC(0-6) is a measure of the area under the serum concentration-time curve from 0 to 6 hours of parathyroid hormone.
(Ca^2+ Ae6): Amount of Calcium Excreted in Urine From Time 0 to 6 Hours Post-dose	Days 3 and 6: pre-dose and at multiple time-points (upto 6 hours) postdose. Day 3 for the noncarbonated water reporting group and Day 6 for the Calcichew D3 reporting group	Ca\^2+ Ae6 was calculated as the urine volume of the urine collected from 0 to 6 hours multiplied by the calcium concentration measured in urine.

Secondary Outcome Measures

Name	Time	Method
PTH AUC (0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours for Parathyroid Hormone	Days 3 and 6: pre-dose and at multiple time-points (up to 24 hours) postdose. Day 3 for the noncarbonated water reporting group and Day 6 for the calcichew D3 reporting group	The PTH AUC(0-24) is a measure of the area under the serum concentration-time curve from 0 to 24 hours of parathyroid hormone.
(Ca^2+ Ae24): Amount of Calcium Excreted in Urine From Time 0 to 24 Hours Post-dose	Days 3 and 6: pre-dose and at multiple time-points (upto 24 hours) postdose. Day 3 for the noncarbonated water reporting group and Day 6 for the Calcichew D3 reporting group	Ca2+ Ae0-24 was calculated as the urine volume of the urine collected from 0 to 24 hours multiplied by the calcium concentration measured in urine.
Cmax: Maximum Observed Serum Concentration for Calcium	Days 3 and 6: predose and at multiple time-points (up to 24 hours) postdose. Day 3 for the non carbonated water reporting group and Day 6 for the Calcichew D3 reporting group
AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Calcium	Days 3 and 6: predose and at multiple time-points (up to 6 hours) postdose. Day 3 for the non carbonated water reporting group and Day 6 for the Calcichew D3 reporting group
AUC(0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Calcium	Days 3 and 6: predose and at multiple time-points (up to 24 hours) postdose. Day 3 for the non carbonated water reporting group and Day 6 for the Calcichew D3 reporting group
Tmax: Time to Reach the Cmax for Calcium	Days 3 and 6: predose and at multiple time-points (up to 24 hours) postdose. Day 3 for the non carbonated water reporting group and Day 6 for the Calcichew D3 reporting group
Number of Participants Who Experience at Least 1 Treatment-Emergent Adverse Event (TEAE)	Baseline up to 14 days after last dose of study drug (Day 21)