Healthy Volunteers
Conditions
Keywords
Drug therapy
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.
Interventions
DRUGCalcichew D3
Calcium 500 mg and vitamin D3 1000 IU chewable tablets
DRUGNoncarbonated Water
Noncarbonated water 200 mL
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 70 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
| 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) | — |
| 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 | — |
| (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. |
Countries
France
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in France from 16 January 2015 to 24 February 2015.
Pre-assignment details
Healthy participants were enrolled in this study. Treatment period of study comprised of 2-periods. Participants received noncarbonated water in period 1 (dummy treatment period) and Calcichew D3 in period 2 (study treatment period).
Participants by arm
| Arm | Count |
|---|---|
| Noncarbonated Water+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. | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Noncarbonated Water+Calcichew D3 |
|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 6.34 |
| Alcohol classification Current Drinker (less than 5 units per day) | 5 participants |
| Alcohol classification Never Drunk | 22 participants |
| Body Mass Index (BMI) | 24.49 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.594 |
| Height | 166.3 centimeter (cm) STANDARD_DEVIATION 9.16 |
| Number of Participants who were Postmenopausal | 14 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 13 Participants |
| Smoking classification Current Smoker | 0 participants |
| Smoking classification Ex-Smoker | 9 participants |
| Smoking classification Never Smoked | 18 participants |
| Weight | 68.0 kilogram (kg) STANDARD_DEVIATION 11.088 |
| Xanthine/Caffeine Consumption Had Consumption | 21 participants |
| Xanthine/Caffeine Consumption Had no Consumption | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 27 | 2 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
(Ca^2+ Ae6): Amount of Calcium Excreted in Urine From Time 0 to 6 Hours Post-dose
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.
Time frame: 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
Population: The pharmacokinetic(PK) urine analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable urine concentration of calcium in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | (Ca^2+ Ae6): Amount of Calcium Excreted in Urine From Time 0 to 6 Hours Post-dose | NA millimoles (mmol) | — |
| Calcichew D3 | (Ca^2+ Ae6): Amount of Calcium Excreted in Urine From Time 0 to 6 Hours Post-dose | 1.74 millimoles (mmol) | Geometric Coefficient of Variation 40.6 |
Primary
PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone
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.
Time frame: 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
Population: The Pharmacodynamic(PD) serum analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable serum concentration of parathyroid hormone in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone | 215 hour*picogram per milliliter (hr*pg/mL) | Geometric Coefficient of Variation 30.3 |
| Calcichew D3 | PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone | 157 hour*picogram per milliliter (hr*pg/mL) | Geometric Coefficient of Variation 31.5 |
Secondary
AUC(0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Calcium
Time frame: 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
Population: The PK serum analysis set of included participants who received at least 1 dose of dummy treatment and had at least 1 measurable serum concentration of calcium in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | AUC(0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Calcium | 53.8 hr*mmol/L | Geometric Coefficient of Variation 2.2 |
| Calcichew D3 | AUC(0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours Post-dose for Calcium | 55.0 hr*mmol/L | Geometric Coefficient of Variation 3 |
Secondary
AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Calcium
Time frame: 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
Population: The PK serum analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable serum concentration of calcium in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Calcium | 13.5 hour*millimoles per litre (hr*mmol/L) | Geometric Coefficient of Variation 2.3 |
| Calcichew D3 | AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Calcium | 13.9 hour*millimoles per litre (hr*mmol/L) | Geometric Coefficient of Variation 2.6 |
Secondary
(Ca^2+ Ae24): Amount of Calcium Excreted in Urine From Time 0 to 24 Hours Post-dose
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.
Time frame: 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
Population: The PK urine analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable urine concentration of calcium in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | (Ca^2+ Ae24): Amount of Calcium Excreted in Urine From Time 0 to 24 Hours Post-dose | 3.21 mmol | Geometric Coefficient of Variation 52.2 |
| Calcichew D3 | (Ca^2+ Ae24): Amount of Calcium Excreted in Urine From Time 0 to 24 Hours Post-dose | 4.67 mmol | Geometric Coefficient of Variation 34.6 |
Secondary
Cmax: Maximum Observed Serum Concentration for Calcium
Time frame: 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
Population: The PK serum analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable serum concentration of calcium in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | Cmax: Maximum Observed Serum Concentration for Calcium | 2.35 millimoles per litre(mmol/L) | Geometric Coefficient of Variation 2.1 |
| Calcichew D3 | Cmax: Maximum Observed Serum Concentration for Calcium | 2.40 millimoles per litre(mmol/L) | Geometric Coefficient of Variation 2.9 |
Secondary
Number of Participants Who Experience at Least 1 Treatment-Emergent Adverse Event (TEAE)
Time frame: Baseline up to 14 days after last dose of study drug (Day 21)
Population: The safety analysis set included all participants who were enrolled and received at least 1 dose of dummy treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Noncarbonated Water | Number of Participants Who Experience at Least 1 Treatment-Emergent Adverse Event (TEAE) | 0 participants |
| Calcichew D3 | Number of Participants Who Experience at Least 1 Treatment-Emergent Adverse Event (TEAE) | 2 participants |
Secondary
PTH AUC (0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours for Parathyroid Hormone
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.
Time frame: 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
Population: The PD serum analysis set included all participants who received at least 1 dose of dummy treatment and had at least 1 measurable serum concentration of parathyroid hormone in each treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | PTH AUC (0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours for Parathyroid Hormone | 1020 hr*pg/mL | Geometric Coefficient of Variation 30.5 |
| Calcichew D3 | PTH AUC (0-24): Area Under the Serum Concentration-Time Curve From Time 0 to 24 Hours for Parathyroid Hormone | 908 hr*pg/mL | Geometric Coefficient of Variation 29.5 |
Secondary
Tmax: Time to Reach the Cmax for Calcium
Time frame: 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
Population: The PK analysis set consisted of all participants who received at least 1 dose of dummy treatment and who had at least 1 measurable serum concentration of calcium in each treatment period.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Noncarbonated Water | Tmax: Time to Reach the Cmax for Calcium | 24.0 hours | Full Range 8.72 |
| Calcichew D3 | Tmax: Time to Reach the Cmax for Calcium | 4.00 hours | Full Range 7.45 |