Trial Outcomes & Findings for Effect of Calcium 500 mg and Vitamin D3 1000 IU Chewable Tablet on Intestinal Calcium Absorption (NCT NCT02338713)

Last Updated: 2017-06-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

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

Results posted on

2017-06-16

Participant Flow

Participants took part in the study at 1 investigative site in France from 16 January 2015 to 24 February 2015.

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).

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	27
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Noncarbonated Water+Calcichew D3 n=27 Participants 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.
Age, Continuous	59.0 years STANDARD_DEVIATION 6.34 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Height	166.3 centimeter (cm) STANDARD_DEVIATION 9.16 • n=5 Participants
Weight	68.0 kilogram (kg) STANDARD_DEVIATION 11.088 • n=5 Participants
Body Mass Index (BMI)	24.49 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.594 • n=5 Participants
Smoking classification Never Smoked	18 participants n=5 Participants
Smoking classification Current Smoker	0 participants n=5 Participants
Smoking classification Ex-Smoker	9 participants n=5 Participants
Alcohol classification Never Drunk	22 participants n=5 Participants
Alcohol classification Current Drinker (less than 5 units per day)	5 participants n=5 Participants
Xanthine/Caffeine Consumption Had Consumption	21 participants n=5 Participants
Xanthine/Caffeine Consumption Had no Consumption	6 participants n=5 Participants
Number of Participants who were Postmenopausal	14 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
PTH AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Parathyroid Hormone	215 hourpicogram per milliliter (hrpg/mL) Geometric Coefficient of Variation 30.3	157 hourpicogram per milliliter (hrpg/mL) Geometric Coefficient of Variation 31.5

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
(Ca^2+ Ae6): Amount of Calcium Excreted in Urine From Time 0 to 6 Hours Post-dose	NA millimoles (mmol) Geometric Coefficient of Variation NA No data was reported since Geometric mean was not calculated when minimum value was '0', as predefined in protocol.	1.74 millimoles (mmol) Geometric Coefficient of Variation 40.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
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	908 hr*pg/mL Geometric Coefficient of Variation 29.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
(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	4.67 mmol Geometric Coefficient of Variation 34.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
Cmax: Maximum Observed Serum Concentration for Calcium	2.35 millimoles per litre(mmol/L) Geometric Coefficient of Variation 2.1	2.40 millimoles per litre(mmol/L) Geometric Coefficient of Variation 2.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
AUC(0-6): Area Under the Serum Concentration-Time Curve From Time 0 to 6 Hours for Calcium	13.5 hourmillimoles per litre (hrmmol/L) Geometric Coefficient of Variation 2.3	13.9 hourmillimoles per litre (hrmmol/L) Geometric Coefficient of Variation 2.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
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	55.0 hr*mmol/L Geometric Coefficient of Variation 3.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
Tmax: Time to Reach the Cmax for Calcium	24.0 hours Full Range 8.72 • Interval 3.0 to 24.0	4.00 hours Full Range 7.45 • Interval 0.517 to 24.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Noncarbonated Water n=27 Participants Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 Participants Calcichew D3 500 mg/1000 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).
Number of Participants Who Experience at Least 1 Treatment-Emergent Adverse Event (TEAE)	0 participants	2 participants

Adverse Events

Noncarbonated Water

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Calcichew D3

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Noncarbonated Water n=27 participants at risk Noncarbonated water 200 mL, orally, once daily on Days 1, 2 and 3 in period 1 (dummy treatment period).	Calcichew D3 n=27 participants at risk Calcichew D3 500 mg/1000 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).
Nervous system disorders Headache	0.00% 0/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 14 days after the last dose of Calcichew D3 study drug (21 days). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.4% 2/27 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 14 days after the last dose of Calcichew D3 study drug (21 days). At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER