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

• ClinicalTrials.gov Identifier: NCT01639222
• Recruitment Status: Completed
• First Posted: July 12, 2012
• Results First Posted: October 18, 2013
• Last Update Posted: October 18, 2013
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Calcium Deficiency; Vitamin D Deficiency
• Interventions: Drug: Calcium 500 mg and Vitamin D3 800 IU; Other: Low calcium meals
• Enrollment: 55

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Calcium 500 mg and Vitamin D3 800 IU
Arm/Group Description	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.
Period Title: Overall Study
Started	55
Completed	55
Not Completed	0

Baseline Characteristics

Arm/Group Title		Calcium 500 mg and Vitamin D3 800 IU
Arm/Group Description		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.
Overall Number of Baseline Participants		55
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	55 participants
		57.07 (7.01)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	55 participants
	Female	22 40.0%
	Male	33 60.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Germany	Number Analyzed	55 participants
		55
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	55 participants
		172.71 (8.97)
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	55 participants
		77.28 (10.06)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kg/m²
	Number Analyzed	55 participants
		25.87 (2.33)
Creatinine Clearance; Mean (Standard Deviation); Unit of measure: mL/min/1.73 m²
	Number Analyzed	55 participants
		86.60 (14.85)

Outcome Measures

1. Primary Outcome

Title	Amount of Calcium Excreted in Urine From 0 Hours up to 6 Hours Post Dose (Ca2+ Ae0-6h)
Description	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.
Time Frame	Day 3 of Period 1 (Reference) and Day 3 in Period 2. Samples were taken 0-6 Hours post dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic/Pharmacodynamic (PK/PD) Set included all enrolled subjects who received at least one dose of the mock treatment who had reliable values of either the primary PK parameter Ca2+ Ae0-6h in both periods or the primary PD parameter PTH AUC0-6h in both periods.

Arm/Group Title	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
Arm/Group Description:	Period 2 (Days 4-6): Calcium 500 mg and Vitamin D3 800 IU chewable tablets, orally, once daily, followed by 200 mL of non-carbonated water, for up to 3 days with low calcium meals.	Period 1 (Days 1-3): 200 mL of non-carbonated water (mock treatment) with low calcium meals for up to 3 days.
Overall Number of Participants Analyzed	55	55
Mean (Standard Deviation); Unit of Measure: mmol
	1.07 (0.49)	0.63 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Calcium 500 mg and Vitamin D3 800 IU, Reference Treatment
	Comments	The primary parameters were analysed in a mixed effects general linear model of the logtransformed values, including treatment as a fixed effect and subject as a random effect. The objective of the trial was met if the treatment contrast was statistically significantly different from 0 in the appropriate direction in a 2-sided test on a 5% significance level for both parameters. The 5% significance level for both primary parameters was not adjusted for multiple testing.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Calcium-Vitamin D/Reference (%)
	Estimated Value	179.72
	Confidence Interval	(2-Sided) 95%; 157.16 to 205.52
	Estimation Comments	Point estimates and 95% CIs for the treatment difference ratio (Calcium-Vitamin D/reference treatment) are provided on the original scale as a ratio * 100%.

2. Primary Outcome

Title	Area Under the Curve From 0 to 6 Hours Post Dose of Parathyroid Hormone (PTH AUC0-6h) in Serum
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

PK/PD set

Arm/Group Title	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
Arm/Group Description:	Period 2 (Days 4-6): Calcium 500 mg and Vitamin D3 800 IU chewable tablets, orally, once daily, followed by 200 mL of non-carbonated water, for up to 3 days with low calcium meals.	Period 1 (Days 1-3): 200 mL of non-carbonated water (mock treatment) with low calcium meals for up to 3 days.
Overall Number of Participants Analyzed	55	55
Mean (Standard Deviation); Unit of Measure: h*pg/mL
	202.02 (63.51)	278.86 (79.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Calcium 500 mg and Vitamin D3 800 IU, Reference Treatment
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Calcium-Vitamin D/Reference (%)
	Estimated Value	71.77
	Confidence Interval	(2-Sided) 95%; 68.83 to 74.84
	Estimation Comments	Point estimate and 95% CI for the treatment difference ratio (Calcium-Vitamin D /reference treatment) are provided on the original scale as a ratio * 100%.

3. Secondary Outcome

Title	Amount of Calcium Excreted in Urine From 0 to 6 Hours Post Dose Corected for Creatinine (Ae0-6h/Creatinine)
Description	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.
Time Frame	Day 3 of Period 1 (Baseline) and Day 3 in Period 2. Samples will be taken 0-6 Hours postdose

Outcome Measure Data

Analysis Population Description

PK/PD set

Arm/Group Title	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
Arm/Group Description:	Period 2 (Days 4-6): Calcium 500 mg and Vitamin D3 800 IU chewable tablets, orally, once daily, followed by 200 mL of non-carbonated water, for up to 3 days with low calcium meals.	Period 1 (Days 1-3): 200 mL of non-carbonated water (mock treatment) with low calcium meals for up to 3 days.
Overall Number of Participants Analyzed	55	55
Mean (Standard Deviation); Unit of Measure: liters
	1.05 (0.92)	0.69 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Calcium 500 mg and Vitamin D3 800 IU
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Calcium-Vitamin D/Reference (%)
	Estimated Value	156.74
	Confidence Interval	(2-Sided) 95%; 121.66 to 201.93
	Estimation Comments	Point estimates and 95% CIs for the treatment difference ratio (Calcium-Vitamin D / reference treatment) are provided on the original scale as a ratio * 100%.

Adverse Events

Time Frame	Up to 13 days.
Adverse Event Reporting Description	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. A safety follow-up phone call was conducted 7 to 12 days after last dosing.
Arm/Group Title	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
Arm/Group Description	Period 2 (Days 4-6): Calcium 500 mg and Vitamin D3 800 IU chewable tablets, orally, once daily, followed by 200 mL of non-carbonated water, for up to 3 days with low calcium meals.	Period 1 (Days 1-3): 200 mL of non-carbonated water (mock treatment) with low calcium meals for up to 3 days.
All-Cause Mortality
	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/55 (0.00%)	0/55 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Calcium 500 mg and Vitamin D3 800 IU	Reference Treatment
	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/55 (9.09%)	6/55 (10.91%)
Gastrointestinal disorders
Diarrhoea † 1	3/55 (5.45%)	0/55 (0.00%)
Constipation † 1	0/55 (0.00%)	1/55 (1.82%)
Investigations
Blood pressure increased † 1	0/55 (0.00%)	1/55 (1.82%)
Musculoskeletal and connective tissue disorders
Back pain † 1	0/55 (0.00%)	1/55 (1.82%)
Nervous system disorders
Headache † 1	1/55 (1.82%)	3/55 (5.45%)
Dizziness † 1	1/55 (1.82%)	0/55 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights therefrom or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda’s sole discretion.

Results Point of Contact

• Name/Title: Sr. VP, Clinical Science
• Organization: Takeda Global Research and Development Center, Inc.
• Phone: 800-778-2860
• EMail: clinicaltrialregistry@tpna.com

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01639222 History of Changes
• Other Study ID Numbers: CW-2200-401-RD; 2011-005786-21 ( EudraCT Number ); U1111-1124-2328 ( Registry Identifier: WHO )
• First Submitted: July 9, 2012
• First Posted: July 12, 2012
• Results First Submitted: March 25, 2013
• Results First Posted: October 18, 2013
• Last Update Posted: October 18, 2013