Clinical Trial Results:
Clinical Trial of pharmacokinetics of calcifediol (25OHD3) in women with postmenopausal osteoporosis
Summary
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EudraCT number |
2015-005303-91 |
Trial protocol |
IT |
Global end of trial date |
25 Sep 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Jun 2021
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First version publication date |
30 Jun 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
VIT_D_2015
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
VIT_D_2015: VIT_D_2015 | ||
Sponsors
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Sponsor organisation name |
Azienda Ospedaliera Universitaria Senese
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Sponsor organisation address |
VIALE MARIO BRACCI 16, Siena, Italy, 53100
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Public contact |
UOC Medicina Interna 1, Prof. Stefano Gonnelli, Azienda Ospedaliera Universitaria Senese, +39 0577585468, gonnelli@unisi.it
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Scientific contact |
UOC Medicina Interna 1, Prof. Stefano Gonnelli, Azienda Ospedaliera Universitaria Senese, +39 0577585468, gonnelli@unisi.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Apr 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Sep 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Sep 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the pharmacokinetic of 25(OH)D3 in postmenopausal women with osteoporosis treated for 6 months with two different dosages of calcifediol.
To evaluate the efficacy of two different dosages of calcifediol in the achievement of serum levels of 25(OH)D3 higher than 30 ng/ml in women with postmenopausal osteoporosis.
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Protection of trial subjects |
Not Applicable
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Background therapy |
Not Applicable | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Apr 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
35
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From 65 to 84 years |
15
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrolment at department of internal Medicine 1 at Univ. Hosp. Siena (From 04/2017 to 02/2019) Postmenopausal women (amenorrhea) for at least 5 years, Age between 55 and 70 years, Lumbar or femoral T-score ≤ -2.5SD, Plasma levels of 25OHD3 between 10 and 20 ng/ml, Informed consenst signed, Willingness and capacity to adhere to study protocol | |||||||||||||||||||||
Pre-assignment
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Screening details |
92 patients were screened, of which 42 excluded for non-compliance with the inclusion criteria - Postmenopausal women (amenorrhea) for at least 5 years - Age between 55 and 70 years - Lumbar or femoral T-score ≤ -2.5 SD - Plasma levels of 25OHD3 between 10 and 20 ng/ml | |||||||||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Blinding implementation details |
Not Applicable
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Low dose Arm | |||||||||||||||||||||
Arm description |
Patients will receive 28 drops per week of calcifediol equal to 140 mcg for six months (= 4 drops per day) Treatment will last 6 months. After 7, 14, 21, 30, 90 and 180 days of therapy respectively, the patient will undergo the scheduled check-ups with evaluation Calcemia, phosphorus, creatinine, calcium, phosphaturia, creatininuria (24 hour urine), total alkaline phosphatase and bone , serum cross-laps, 25OHD, 1.25 (OH) 2D3 and PTH. Muscle strength evaluation by Hand-grip. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Calcifediol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral drops, suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Patients will receive 28 drops of calcifediol (oral use) per week equal to 140 mcg for six months.
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Arm title
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High dose Arm | |||||||||||||||||||||
Arm description |
Patients will receive 42 drops per week of calcifediol equal to 210 mcg for six months (= 4 drops per day) Treatment will last 6 months. After 7, 14, 21, 30, 90 and 180 days of therapy respectively, the patient will undergo the scheduled check-ups with evaluation Calcemia, phosphorus, creatinine, calcium, phosphaturia, creatininuria (24 hour urine), total alkaline phosphatase and bone , serum cross-laps, 25OHD, 1.25 (OH) 2D3 and PTH. Muscle strength evaluation by Hand-grip. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Calcifediol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral drops, suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Patients will receive 42 drops of calcifediol (oral use) per week equal to 210 mcg for six months.
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Baseline characteristics reporting groups
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Reporting group title |
Low dose Arm
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Reporting group description |
Patients will receive 28 drops per week of calcifediol equal to 140 mcg for six months (= 4 drops per day) Treatment will last 6 months. After 7, 14, 21, 30, 90 and 180 days of therapy respectively, the patient will undergo the scheduled check-ups with evaluation Calcemia, phosphorus, creatinine, calcium, phosphaturia, creatininuria (24 hour urine), total alkaline phosphatase and bone , serum cross-laps, 25OHD, 1.25 (OH) 2D3 and PTH. Muscle strength evaluation by Hand-grip. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
High dose Arm
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Reporting group description |
Patients will receive 42 drops per week of calcifediol equal to 210 mcg for six months (= 4 drops per day) Treatment will last 6 months. After 7, 14, 21, 30, 90 and 180 days of therapy respectively, the patient will undergo the scheduled check-ups with evaluation Calcemia, phosphorus, creatinine, calcium, phosphaturia, creatininuria (24 hour urine), total alkaline phosphatase and bone , serum cross-laps, 25OHD, 1.25 (OH) 2D3 and PTH. Muscle strength evaluation by Hand-grip. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Analysys Anova
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
For the comparison between the two independent groups of the study, the T-test will be used, or, if necessary, the non-parametric equivalent of the Mann-Whitney test
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End points reporting groups
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Reporting group title |
Low dose Arm
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Reporting group description |
Patients will receive 28 drops per week of calcifediol equal to 140 mcg for six months (= 4 drops per day) Treatment will last 6 months. After 7, 14, 21, 30, 90 and 180 days of therapy respectively, the patient will undergo the scheduled check-ups with evaluation Calcemia, phosphorus, creatinine, calcium, phosphaturia, creatininuria (24 hour urine), total alkaline phosphatase and bone , serum cross-laps, 25OHD, 1.25 (OH) 2D3 and PTH. Muscle strength evaluation by Hand-grip. | ||
Reporting group title |
High dose Arm
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Reporting group description |
Patients will receive 42 drops per week of calcifediol equal to 210 mcg for six months (= 4 drops per day) Treatment will last 6 months. After 7, 14, 21, 30, 90 and 180 days of therapy respectively, the patient will undergo the scheduled check-ups with evaluation Calcemia, phosphorus, creatinine, calcium, phosphaturia, creatininuria (24 hour urine), total alkaline phosphatase and bone , serum cross-laps, 25OHD, 1.25 (OH) 2D3 and PTH. Muscle strength evaluation by Hand-grip. | ||
Subject analysis set title |
Analysys Anova
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
For the comparison between the two independent groups of the study, the T-test will be used, or, if necessary, the non-parametric equivalent of the Mann-Whitney test
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End point title |
25OHD3 serum levels at 180 days | ||||||||||||||||
End point description |
25OHD3 serum levels at 180 days
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End point type |
Primary
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End point timeframe |
25OHD3 serum levels at baseline and 15, 30, 60, 90, 180 days
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Statistical analysis title |
Analysis Anova 25OHD3 serum levels at 180 days | ||||||||||||||||
Statistical analysis description |
Evaluation also at 15, 30, 60, 90 days
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Comparison groups |
Low dose Arm v High dose Arm
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
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End point title |
1-25OHD2 serum levels at 180 days | ||||||||||||||||
End point description |
1-25OHD2 serum levels at 180 days
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End point type |
Secondary
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End point timeframe |
1-25OHD2 serum levels at baseline and 15, 30, 60, 90, 180 days
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Statistical analysis title |
Analysis 1-25OHD2 Anova at 180 days | ||||||||||||||||
Comparison groups |
High dose Arm v Low dose Arm
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
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End point title |
Calcemia at 180 days | ||||||||||||||||
End point description |
Serum Total Calcium at 180 days
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End point type |
Secondary
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End point timeframe |
Serum Total Calcium at baseline and 15, 30, 60, 90, 180 days
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Statistical analysis title |
Analysis Calcemia Anova at 180 days | ||||||||||||||||
Statistical analysis description |
Evaluation also at 15, 30, 60, 90 days
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Comparison groups |
Low dose Arm v High dose Arm
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
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End point title |
Calciuria at 180 days | ||||||||||||||||
End point description |
Calciuria at 180 days
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End point type |
Secondary
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End point timeframe |
Calciuria at baseline and 30, 60, 90, 180 days
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Statistical analysis title |
Calciuria at 180 days Anova Test | ||||||||||||||||
Statistical analysis description |
Evaluation also at 15, 30, 60, 90 days
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Comparison groups |
High dose Arm v Low dose Arm
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
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End point title |
Muscle strenght (Handgrip) at 180 days | ||||||||||||||||
End point description |
Muscle strenght (Handgrip) at 180 days
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End point type |
Secondary
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End point timeframe |
Muscle strenght (Handgrip) at baseline and 30, 60, 90, 180 days
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Statistical analysis title |
Handgrip Anova Analysis at 180 days | ||||||||||||||||
Statistical analysis description |
Evaluation also at 15, 30, 60, 90 days
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Comparison groups |
High dose Arm v Low dose Arm
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Number of subjects included in analysis |
46
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Evaluation of side effects at all visits
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Assessment type |
Systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Low dose arm
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Reporting group description |
- | |||||||||||||||||||||
Reporting group title |
High dose arm
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Reporting group description |
- | |||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/33506314 |