Phase IV randomized preference study in patients eligible for calcium and vitamin D supplementation

Abstract

Introduction/objectives: 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 D3¹ 500 mg/400 IU and Calcichew D3 500 mg/800 IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D3² 500 mg/400 IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500 mg/800 IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively.

Method: 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.

Trial registration: Clinicaltrials.gov: NCT02457247.

Keywords:

• Acceptability; Calcium; Osteoporosis; Preference; Supplement; Vitamin D

Notes

Transparency

Declaration of funding

Takeda is the trial sponsor and performed the statistical analyses for the studies.

Author contributions: The studies were led by F.T. and P.I. T.K.N. performed statistical analyses on the study data. All authors took part in drafting the manuscript, had access to all the data and guarantee the analyses and manuscript.

Declaration of financial/other relationships

F.T. and P.I. have disclosed that they are employees of Synexus, a company that helped develop this study, with funding from Takeda Pharmaceutical Company. F.T. has disclosed that he has also served on speaker bureaus for Amgen and Lilly and is an Advisor for Amgen. T.K.N. has disclosed that he is an employee of Takeda.

CMRO peer reviewer 1 is a CMRO Editorial Board Member. Peer reviewers 2 and 3 have no relevant financial or other relationships to disclose.

Acknowledgments

Katie Greenhalgh of Synergy Vision provided editorial assistance with the manuscript, supported by Takeda Development Centre Europe Ltd, London, UK.

Notes

1 Calcichew D3 is a registered trade name of Takeda UK Ltd, Woburn Green, UK.

2 Adcal-D3 is a registered trade name of ProStrakan Ltd, Galashiels, UK.

3 Kalcipos-D is a registered trade name of Meda Pharmaceuticals Ltd, Bishop's Stortford, UK.

4 Calcichew D3 Forte is a registered trade name of Takeda UK Ltd, Woburn Green, UK.