CompletedPhase 1ACTRN12621001521819

Development of an Oral Preparation of Zoledronic Acid for Use in Postmenopausal Osteoporosis/Osteopenia

Development of an Oral Preparation of Zoledronic Acid for Use in Postmenopausal Osteoporosis/Osteopenia: Dose-Finding Study

Sponsor

The University of Auckland

Enrollment

30 participants

Start Date

May 20, 2019

Study Type

Interventional

Conditions

Osteoporosis Osteopenia

Summary

Intravenous (IV) zoledronate is an effective and widely used treatment for osteoporosis. Zoledronate is the most potent bisphosphonate to enter clinical practice, and it also has the longest duration of anti-resorptive effect, with a single 5mg infusion still showing effects on bone turnover and bone mineral density (BMD) 5 years later. Duration of effect is, to some extent, dose-related. However, the need for an intravenous infusion is a disadvantage in some environments, such as general practices, where facilities for infusions are difficult to access or, in some countries, very expensive. A second problem with intravenous zoledronate is the occurrence of an acute phase response, a flu-like illness that occurs in 30-40% of those having first infusions. Oral zoledronate is potentially attractive for the prevention and treatment of osteoporosis, but has not been investigated to-date. It would be much more accessible, since infusion facilities would not be necessary for its administration. If the acute phase response is indeed much less common, then this would remove the other main limitation in the clinical use of zoledronate. The overall goal of this study is to establish a dosing regimen using zoledronate tablets that reproduces the bone turnover marker and bone density effects over 1 year of a zoledronate 5 mg infusion.

Eligibility

Sex: FemalesMin Age: 55 Yearss

Inclusion Criteria1

Healthy women > 5 years post menopause, or >55 years of age if hysterectomised

Exclusion Criteria18

Renal impairment (eGFR less than 40 mL/minute)
Active upper gastro-intestinal disease or persistent dyspeptic symptoms
Hypocalcaemia
Risk factors for severe vitamin D deficiency (frail elderly, absence of regular times outdoors, veiling, South Asian/Middle Eastern/African origin not using vitamin D supplements. If any of these risk factors are present then calciferol 100,000 IU will be administered as a single dose at least 3 days before dosing with the trial medication.
Active dental disease likely to require invasive treatment during the trial period. The possibility of needing tooth fillings is not an exclusion.
Active inflammatory disease of the eye
History of an atypical femoral fracture, as defined by the ASBMR 2013
Untreated hypo- or hyperthyroidism
Active liver disease
Concurrent major systemic disease
Active malignancy (other than skin cancers) within the last 2 years
Any active metabolic bone disease
Regular use of hormone replacement therapy within the previous 1 year
Treatment with oral bisphosphonates in the previous 1 year
Previous treatment with zoledronate at any time
Current treatment with oral glucocorticoid drugs in a dose greater than or equal to 2.5 mg/day
Regular use of other bone-active drugs in the previous year ( e.g. teriparatide, raloxifene, tamoxifen, aromatase inhibitors)
Malabsorption syndromes

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Interventions

Arm 1:20mg enteric coated oral zoledronate capsule- one dose only at baseline. Arm 2: 20mg enteric coated micro-capsulated oral zoledronate capsule- one dose only at baseline Arm 3: 40mg enteric coa

Arm 1:20mg enteric coated oral zoledronate capsule- one dose only at baseline. Arm 2: 20mg enteric coated micro-capsulated oral zoledronate capsule- one dose only at baseline Arm 3: 40mg enteric coated oral zoledronate capsule- one dose only at baseline Arm 4: 20mg enteric coated micro-capsulated oral zoledronate capsule- one dose at baseline and one week Arm 5: 20mg enteric coated oral zoledronate capsule, one capsule at baseline and 40mg at 1 week Arm 6: 20mg enteric coated micro-capsulated oral zoledronate capsule at baseline, one week and two weeks. The first dose will be administered on site under monitoring and in those who are getting further doses, the subsequent capsules are taken at home. This is a dose ranging study and the outcomes will be compared to the effect of a standard 5mg intravenous dose of Zoledronate. The first 5 participants recruited will join Arm 1, then the next 5 will be in arm 2 and so on until we establish the most effective dose.