Phase IV randomized preference study in patients eligible for calcium and vitamin D supplementation.
OBJECTIVE
Preference for supplement formulation helps determine an individual's adherence to long-term medication and can improve clinical benefit for chronic illnesses such as osteoporosis. This study compared the preference, acceptability and tolerability of a reformulation of Calcichew D31500 mg/400 IU and Calcichew D3 500 mg/800 IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D32500 mg/400 IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500 mg/800 IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively.


METHODS
This phase IV, randomized, open-label, two-period, cross-over study was conducted at nine sites in the UK and Germany. Eligible subjects (≥65 years requiring calcium/vitamin D supplementation for prevention/treatment of deficiencies, or ≥18 years requiring supplementation as an adjunct to osteoporosis treatment) were randomly assigned to one of two 2 week treatment sequences - Group 1: Calcichew D3 500/400 then Adcal-D3 500/400 (or vice versa), or Group 2: Calcichew D3 500/800 then Kalcipos-D 500/800 (or vice versa). After each treatment period, patients rated the treatment for acceptability using 100 mm visual analogue scales. After the second treatment period, patients indicated their treatment preference. The primary endpoint, the percentage of patients with a preference for each treatment, was analyzed with a logistic regression model.


RESULTS
Two hundred and seventy-six patients were randomly assigned by treatment sequence, 138 to each group. Preference questionnaires among patients who preferred Calcichew or comparator revealed the odds for patients preferring Calcichew 500/400 (77.6%) over Adcal-D3 was 3.46 ([95% CI 2.24, 5.36], p < 0.001) in Group 1, and Calcichew D3 500/800 (63.2%) over Kalcipos-D was 1.72 ([1.19, 2.47], p = 0.004) in Group 2. Adverse events were mostly gastrointestinal and were comparable between groups. The new formulation of Calcichew D3 is acceptable and consistent with its known tolerability profile.


CONCLUSIONS
In this short-term 30 day study, patients preferred Calcichew D3 500/400 and Calcichew D3 500/800 over respective comparators. A trend towards better compliance with Calcichew D3 preference observed in Group 1 warrants a longer term study to identify treatment compliance.


BACKGROUND
Clinicaltrials.gov: NCT02457247.
a Synexus Clinical Research , Frankfurt , Germany.
Friederike
F
Thomasius
b Takeda Development Centre Europe Ltd , London , UK.
Tsz
T
Keung Nip
c Synexus Merseyside Medical Research Centre , Liverpool , UK.
Paul
P
Ivan
Acceptability; Calcium; Osteoporosis; Preference; Supplement; Vitamin D