Calcium and Vitamin D Deficiencies
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to compare the preference of Calcichew D3 500/400 (containing 500 mg calcium and 400 IU of vitamin D) with Adcal-D3 600/400 (containing 600 mg of calcium and 400 IU of vitamin D) in Test Group 1, and to compare Calcichew D3 500/800 (containing 500 mg calcium and 800 IU vitamin D) with Kalcipos-D 500/800 (containing 500 mg of calcium and 800 IU of vitamin D) in Test Group 2.
Detailed description
The drug being tested in this study is called Calcichew D3 new formulations: Calcichew D3 500/400 and Calcichew D3 500/800. Calcichew D3 500/400 and Calcichew D3 500/800 are being tested to treat or prevent calcium or vitamin D deficiencies. Calcichew D3 500/400 will be compared to Adcal-D3 600/400 as prescribed in clinical practice and Calcichew D3 500/800 will be compared to Kalcipos-D 500/800 as prescribed in clinical practice. This Crossover study will enroll approximately 276 patients equally divided between the two test groups (138 patients each). Within each test group, participants will be randomly assigned (by chance, like flipping a coin) to one of two treatment sequences, as described below. Test Group 1: * Calcichew D3 500/400 (containing 500 mg calcium and 400 IU of vitamin D) chewable tablet * Adcal-D3 600/400 (containing 600 mg of calcium and 400 IU of vitamin D) chewable tablet Test Group 2: * Calcichew D3 500/800 (containing 500 mg calcium and 800 IU vitamin D) chewable tablets * Kalcipos-D 500/800 (containing 500 mg of calcium and 800 IU of vitamin D) chewable tablets Participants in Test Group 1 will take either Calcichew D3 500/400 or Adcal-D3 600/400 for 14 days and then will crossover to take either Calcichew D3 500/400 or Adcal-D3 600/400 treatment for 14 days. Participants in Test Group 2 will take either Calcichew D3 500/800 or Kalcipos-D 600/400 for 14 days and then will crossover to take either Calcichew D3 500/800 or Kalcipos-D treatment for 14 days. This multi-center trial will be conducted In the United Kingdom and Germany. The overall time to participate in this study is 28 days. Participants will make multiple visits to the clinic including a final visit assessment at Day 28.
Interventions
DRUGCalcichew D3
Calcichew D3 500/400 (Calcium 500 mg/400 IU Vitamin D3) Calcichew D3 500/800 (Calcium 500 mg/800 IU Vitamin D3)
DRUGAdcal-D3
Adcal-D3 (Calcium 600mg/400 IU Vitamin D3)
DRUGKalcipos-D
Kalcipos-D (Calcium 500mg/800 IU Vitamin D3)
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Is eligible for or currently receiving treatment with calcium and vitamin D supplement as determined by the treating clinician in accordance with local treatment guidelines. 4. Eligible participants will either be: 1. Aged 65 years or older requiring calcium and vitamin D supplementation for the prevention or treatment of deficiencies, or 2. Aged 18 years or older that require calcium and vitamin D as an adjunct to specific osteoporosis treatment in participants at risk of calcium and vitamin D deficiencies. 5. Is male or female. 6. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study, and for 12 weeks after last dose of study medication.
Exclusion criteria
1. Has received Calcichew D3, Adcal-D3 (if the participant is in Test Group 1) or Kalcipos-D (if the participant is in Test Group 2) within the 6 months prior to the first dose of study medication. 2. Has received any investigational compound within 30 days prior to Screening. 3. Has a disease and/or condition resulting in hypercalcaemia and/or hypercalciuria and for which the study drugs are contraindicated e.g. Zollinger-Ellison syndrome, nephrolithiasis. 4. Has any of the contraindications listed in the corresponding Summary of Product Characteristics (SPC) of the study drug that the participant may receive depending on the Test Group: Calcichew D3 or Adcal-D3 (if the participant is in Test Group 1); Calcichew D3 or Kalcipos-D (if the participant is in Test Group 2). 5. Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 6. Has a history of hypersensitivity or allergies to the active substances or to any of the excipients in the investigational products. 7. Has a history of known fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency. 8. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during such time period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Day 28 | Preference was assessed by a 3 box questionnaire. Participants checked off one of the boxes: I prefer the first product that was tested, I prefer the second product that was tested or I have no preference. Test Group 1 (United Kingdom): Calcichew D3 is 500/400 and the comparator is Adcal-D3. Test Group 2 (Germany): Calcichew D3 is 500/800 and the comparator is Kalcipos-D. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Day 14 and Day 28 | Product acceptability was assessed by a 6 item questionnaire evaluating the characteristics of the product: gritty, chalky, sweet, ease of chew, ease of swallow and sticky. Using a 100 mm visual analog scale (VAS) the participant put a vertical line through each horizontal line that best describes their level of agreement with each item using a 0 to 100 scale where: 0=far left of the line (best) to 100= far right of the line (worst). Linear mixed model was used for analysis with treatment and period as fixed effects and participants as a random effect. |
| Product Tolerability Expressed as the Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event Within Each Test Group | Day 1 to Day 28 | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Countries
Germany, United Kingdom
Participant flow
Recruitment details
Participants took part in the study at 9 investigative sites in the United Kingdom and Germany from 02 June 2015 to 27 August 2015.
Pre-assignment details
Participants eligible for Vitamin D and Calcium supplements were enrolled equally in 1 of 2 Test Groups to determine the preference between 2 treatments. Group 1: Calcichew D3 500/400 and Adcal-D3 600/400 or Group 2: Calcichew D3 500/800 and Kalcipos-D 500/800.
Participants by arm
| Arm | Count |
|---|---|
| Test Group 1: Sequence AB Calcichew D3 500/400 (Calcium 500 mg/400 IU Vitamin D3) \[A\], chewable tablets, orally, twice, daily, on Days 1 through 14, followed by Adcal-D3 (Calcium 600 mg / 400 IU Vitamin D3) \[B\], chewable tablets, orally, twice, daily, on Days 15 through 28. | 68 |
| Test Group 1: Sequence BA Adcal-D3 (Calcium 600 mg / 400 IU Vitamin D3), chewable tablets, orally, twice, daily, on Days 1 through 14, followed by, Calcichew D3 500/400 (Calcium 500 mg/400 IU Vitamin D3), chewable tablets, orally, twice, daily, on Days 15 through 28. | 70 |
| Test Group 2: Sequence CD Calcichew D3 500/800 (Calcium 500 mg/800 IU Vitamin D3) \[C\], chewable tablets, orally, once, daily, on Days 1 through 14, followed by Kalcipos-D (Calcium 500 mg/800 IU Vitamin D3) \[D\], chewable tablets, orally, once, daily, on Days 15 through 28. | 68 |
| Test Group 2: Sequence DC Kalcipos-D (Calcium 500 mg/800 IU Vitamin D3), chewable tablets, orally, once, daily, on Days 1 through 14, followed by, Calcichew D3 500/800 (Calcium 500 mg/800 IU Vitamin D3), chewable tablets, orally, once, daily, on Days 15 through 28. | 70 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Pretreatment Event/Adverse Event | 0 | 1 | 0 | 0 |
| Period 1 | Significant Protocol Deviation | 1 | 1 | 0 | 0 |
| Period 1 | Voluntary Withdrawal | 1 | 0 | 0 | 0 |
| Period 2 | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Period 2 | Pretreatment Event/Adverse Event | 0 | 1 | 0 | 0 |
| Period 2 | Significant Protocol Deviation | 1 | 0 | 0 | 0 |
| Period 2 | Voluntary Withdrawal | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Test Group 1: Sequence AB | Test Group 1: Sequence BA | Test Group 2: Sequence CD | Test Group 2: Sequence DC | Total |
|---|---|---|---|---|---|
| Age, Continuous | 70.9 years STANDARD_DEVIATION 7.37 | 70.8 years STANDARD_DEVIATION 4.94 | 70.9 years STANDARD_DEVIATION 7.37 | 69.9 years STANDARD_DEVIATION 7.03 | NA years |
| Age, Customized <65 years | 0 participants | 0 participants | 8 participants | 11 participants | 19 participants |
| Age, Customized ≥65 years | 68 participants | 70 participants | 60 participants | 59 participants | 257 participants |
| Age, Customized 85 Years and Over | 0 participants | 1 participants | 2 participants | 0 participants | 3 participants |
| Age, Customized Adults (18-64 Years) | 0 participants | 0 participants | 8 participants | 11 participants | 19 participants |
| Age, Customized From 65-84 Years | 68 participants | 69 participants | 58 participants | 59 participants | 254 participants |
| Alcohol Status Current Drinker | 53 participants | 46 participants | 53 participants | 56 participants | 208 participants |
| Alcohol Status Ex-drinker | 4 participants | 10 participants | 5 participants | 2 participants | 21 participants |
| Alcohol Status Never Drank | 11 participants | 14 participants | 10 participants | 12 participants | 47 participants |
| BMI Categorical <25 kg/m^2 | 11 participants | 17 participants | 30 participants | 27 participants | 85 participants |
| BMI Categorical 25 to <30 kg/m^2 | 30 participants | 29 participants | 27 participants | 27 participants | 113 participants |
| BMI Categorical ≥30 kg/m^2 | 24 participants | 24 participants | 11 participants | 16 participants | 75 participants |
| BMI Categorical Missing | 3 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Body Mass Index (BMI) | 29.157 kg/m^2 STANDARD_DEVIATION 4.7766 | 29.588 kg/m^2 STANDARD_DEVIATION 6.571 | 26.478 kg/m^2 STANDARD_DEVIATION 4.2362 | 27.002 kg/m^2 STANDARD_DEVIATION 5.1081 | NA kg/m^2 |
| Height | 164.4 cm STANDARD_DEVIATION 7.44 | 165.4 cm STANDARD_DEVIATION 8.95 | 164.0 cm STANDARD_DEVIATION 7.73 | 164.8 cm STANDARD_DEVIATION 7.78 | NA cm |
| History of Fractures in the Last 10 Years No | 57 participants | 60 participants | 61 participants | 62 participants | 240 participants |
| History of Fractures in the Last 10 Years Yes | 11 participants | 10 participants | 7 participants | 8 participants | 36 participants |
| History of Osteopenia No | 61 participants | 67 participants | 61 participants | 58 participants | 247 participants |
| History of Osteopenia Yes | 7 participants | 3 participants | 7 participants | 12 participants | 29 participants |
| History of Osteoporosis No | 67 participants | 67 participants | 40 participants | 46 participants | 220 participants |
| History of Osteoporosis Yes | 1 participants | 3 participants | 28 participants | 24 participants | 56 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 3 participants | 0 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 67 participants | 66 participants | 68 participants | 69 participants | 270 participants |
| Region of Enrollment Germany | 0 participants | 0 participants | 68 participants | 70 participants | 138 participants |
| Region of Enrollment United Kingdom | 68 participants | 70 participants | 0 participants | 0 participants | 138 participants |
| Sex: Female, Male Female | 40 Participants | 41 Participants | 60 Participants | 60 Participants | 201 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 8 Participants | 10 Participants | 75 Participants |
| Smoking Status Current Smoker | 8 participants | 6 participants | 9 participants | 11 participants | 34 participants |
| Smoking Status Ex-smoker | 32 participants | 33 participants | 18 participants | 24 participants | 107 participants |
| Smoking Status Never Smoked | 28 participants | 31 participants | 41 participants | 35 participants | 135 participants |
| Weight | 78.92 kg STANDARD_DEVIATION 15.383 | 81.72 kg STANDARD_DEVIATION 23.559 | 71.44 kg STANDARD_DEVIATION 13.799 | 73.61 kg STANDARD_DEVIATION 16.34 | NA kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 135 | 5 / 136 | 0 / 138 | 0 / 138 |
| serious Total, serious adverse events | 1 / 135 | 0 / 136 | 0 / 138 | 0 / 138 |
Outcome results
Primary
Percentage of Participants With a Preference for Each Treatment Within Each Test Group
Preference was assessed by a 3 box questionnaire. Participants checked off one of the boxes: I prefer the first product that was tested, I prefer the second product that was tested or I have no preference. Test Group 1 (United Kingdom): Calcichew D3 is 500/400 and the comparator is Adcal-D3. Test Group 2 (Germany): Calcichew D3 is 500/800 and the comparator is Kalcipos-D.
Time frame: Day 28
Population: All randomized participants from the Full Analysis Set (FAS) who received at least 1 dose of study medication and responded to the preference questionnaire.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Test Group 1: Sequence AB | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Comparator | 28.1 percentage of participants |
| Test Group 1: Sequence AB | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Calcichew D3 | 67.2 percentage of participants |
| Test Group 1: Sequence AB | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | No Preference | 4.7 percentage of participants |
| Test Group 1: Sequence BA | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Comparator | 12.3 percentage of participants |
| Test Group 1: Sequence BA | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Calcichew D3 | 72.3 percentage of participants |
| Test Group 1: Sequence BA | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | No Preference | 15.4 percentage of participants |
| Test Group 2: Sequence CD | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Comparator | 29.4 percentage of participants |
| Test Group 2: Sequence CD | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Calcichew D3 | 61.8 percentage of participants |
| Test Group 2: Sequence CD | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | No Preference | 8.8 percentage of participants |
| Test Group 2: Sequence DC | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Comparator | 37.1 percentage of participants |
| Test Group 2: Sequence DC | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Calcichew D3 | 52.9 percentage of participants |
| Test Group 2: Sequence DC | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | No Preference | 10.0 percentage of participants |
| Test Group 1: Total | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Comparator | 20.2 percentage of participants |
| Test Group 1: Total | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Calcichew D3 | 69.8 percentage of participants |
| Test Group 1: Total | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | No Preference | 10.1 percentage of participants |
| Test Group 2: Total | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Calcichew D3 | 57.2 percentage of participants |
| Test Group 2: Total | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | No Preference | 9.4 percentage of participants |
| Test Group 2: Total | Percentage of Participants With a Preference for Each Treatment Within Each Test Group | Preference for Comparator | 33.3 percentage of participants |
Secondary
Product Acceptability After Each 14 Day Dosing Period Within Each Test Group
Product acceptability was assessed by a 6 item questionnaire evaluating the characteristics of the product: gritty, chalky, sweet, ease of chew, ease of swallow and sticky. Using a 100 mm visual analog scale (VAS) the participant put a vertical line through each horizontal line that best describes their level of agreement with each item using a 0 to 100 scale where: 0=far left of the line (best) to 100= far right of the line (worst). Linear mixed model was used for analysis with treatment and period as fixed effects and participants as a random effect.
Time frame: Day 14 and Day 28
Population: The FAS included all randomized participants.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Test Group 1: Sequence AB | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Gritty | 19.2 mm | Standard Error 2.18 |
| Test Group 1: Sequence AB | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chalky | 23.2 mm | Standard Error 2.49 |
| Test Group 1: Sequence AB | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sweet/Bitter | 32.5 mm | Standard Error 1.74 |
| Test Group 1: Sequence AB | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chew | 8.1 mm | Standard Error 1.62 |
| Test Group 1: Sequence AB | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Swallow | 10.8 mm | Standard Error 2.01 |
| Test Group 1: Sequence AB | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sticky | 6.1 mm | Standard Error 1.22 |
| Test Group 1: Sequence BA | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sticky | 10.9 mm | Standard Error 1.22 |
| Test Group 1: Sequence BA | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chew | 18.1 mm | Standard Error 1.62 |
| Test Group 1: Sequence BA | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Gritty | 24.6 mm | Standard Error 2.18 |
| Test Group 1: Sequence BA | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sweet/Bitter | 34.5 mm | Standard Error 1.74 |
| Test Group 1: Sequence BA | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chalky | 41.1 mm | Standard Error 2.49 |
| Test Group 1: Sequence BA | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Swallow | 20.5 mm | Standard Error 2 |
| Test Group 2: Sequence CD | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chalky | 25.9 mm | Standard Error 2.43 |
| Test Group 2: Sequence CD | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sweet/Bitter | 34.1 mm | Standard Error 1.67 |
| Test Group 2: Sequence CD | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chew | 12.2 mm | Standard Error 1.77 |
| Test Group 2: Sequence CD | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sticky | 8.2 mm | Standard Error 1.16 |
| Test Group 2: Sequence CD | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Swallow | 11.0 mm | Standard Error 1.88 |
| Test Group 2: Sequence CD | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Gritty | 28.4 mm | Standard Error 2.28 |
| Test Group 2: Sequence DC | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Swallow | 19.5 mm | Standard Error 1.89 |
| Test Group 2: Sequence DC | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sticky | 8.4 mm | Standard Error 1.16 |
| Test Group 2: Sequence DC | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chalky | 29.9 mm | Standard Error 2.43 |
| Test Group 2: Sequence DC | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Chew | 19.0 mm | Standard Error 1.78 |
| Test Group 2: Sequence DC | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Gritty | 27.0 mm | Standard Error 2.28 |
| Test Group 2: Sequence DC | Product Acceptability After Each 14 Day Dosing Period Within Each Test Group | Sweet/Bitter | 38.0 mm | Standard Error 1.67 |
Secondary
Product Tolerability Expressed as the Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event Within Each Test Group
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Day 1 to Day 28
Population: The Safety Analysis Set included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Test Group 1: Sequence AB | Product Tolerability Expressed as the Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event Within Each Test Group | 14.8 percentage of participants |
| Test Group 1: Sequence BA | Product Tolerability Expressed as the Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event Within Each Test Group | 9.6 percentage of participants |
| Test Group 2: Sequence CD | Product Tolerability Expressed as the Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event Within Each Test Group | 5.1 percentage of participants |
| Test Group 2: Sequence DC | Product Tolerability Expressed as the Percentage of Participants Who Experience at Least One Treatment-Emergent Adverse Event Within Each Test Group | 4.3 percentage of participants |