Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001521819
Ethics application status
Approved
Date submitted
15/09/2021
Date registered
9/11/2021
Date last updated
20/10/2022
Date data sharing statement initially provided
9/11/2021
Date results information initially provided
9/11/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Development of an Oral Preparation of Zoledronic Acid for Use in Postmenopausal Osteoporosis/Osteopenia
Scientific title
Development of an Oral Preparation of Zoledronic Acid for Use in Postmenopausal Osteoporosis/Osteopenia: Dose-Finding Study
Secondary ID [1] 305255 0
None
Universal Trial Number (UTN)
U1111-1269-3016
Trial acronym
N/A
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 323529 0
Osteopenia 323530 0
Condition category
Condition code
Metabolic and Endocrine 321092 321092 0 0
Other endocrine disorders
Musculoskeletal 321093 321093 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 321648 0
Treatment: Drugs
Comparator / control treatment
No control group. The bone marker response for each dose will be compared to the known effect of a 5mg intravenous dose of Zoledronate.
Control group
Dose comparison

Outcomes
Primary outcome [1] 328872 0
Percent change in plasma CTX on each dosing regimen
Timepoint [1] 328872 0
1,3,6,9 and 12 months after baseline dosing complete. The percent change in CTX from baseline at month 1 is the primary endpoint of this study.
Primary outcome [2] 328874 0
Percent change in plasma P1NP on each dosing regimen
Timepoint [2] 328874 0
3,6,9,12 months after baseline dosing complete The percent change in P1NP from baseline at month 3 a primary endpoint of this study.
Primary outcome [3] 328875 0
Frequency and severity of Acute Phase Reactions for each dosing regimen as assessed by a telephone contact asking specifically about self reported headache, nausea, muscle or joint aches, fever or any other reported symptoms.
Timepoint [3] 328875 0
3 days post completion of dose regimen and until symptoms resolve assessed by ongoing weekly telephone visits and at 3,6,9,12 months after baseline dosing complete.
Secondary outcome [1] 400735 0
Percent change in Bone Mineral Density measurement using a Prodigy DXA scanner at 12 months at spine.
Timepoint [1] 400735 0
12 months after baseline dosing complete.
Secondary outcome [2] 402393 0
Percent change in Bone Mineral Density measurement using a Prodigy DXA scanner at 12 months at total hip.
Timepoint [2] 402393 0
12 months after baseline dosing complete

Eligibility
Key inclusion criteria
Healthy women > 5 years post menopause, or >55 years of age if hysterectomised
Minimum age
55 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Power
Previous studies conducted by our group in osteopenic postmenopausal women indicate that 5 participants provide a power of 90% to detect a change in CTX of this magnitude.

Analysis
Follow-up CTX values will be expressed as a percent of baseline and the mean percent change calculated and tested against zero by t-test.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
20/05/2019
Date of last participant enrolment
Anticipated
Actual
21/12/2020
Date of last data collection
Anticipated
21/12/2021
Actual
25/06/2021
Sample size
Target
30
Accrual to date
Final
30
Recruitment outside Australia
Country [1] 24104 0
New Zealand
State/province [1] 24104 0
Auckland

Funding & Sponsors
Funding source category [1] 309624 0
University
Name [1] 309624 0
The University of Auckland
Country [1] 309624 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 92019, Auckland 1142, New Zealand.
Country
New Zealand
Secondary sponsor category [1] 310649 0
None
Name [1] 310649 0
Address [1] 310649 0
Country [1] 310649 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309399 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 309399 0
133 Molesworth Street
PO Box 5013
Wellington 6140
Ethics committee country [1] 309399 0
New Zealand
Date submitted for ethics approval [1] 309399 0
23/01/2019
Approval date [1] 309399 0
27/03/2019
Ethics approval number [1] 309399 0
19/NTB/13

Summary
Brief 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114018 0
Prof Ian Reid
Address 114018 0
The University of Auckland
Private Bag 92019
Auckland 1142
Country 114018 0
New Zealand
Phone 114018 0
+64 21855160
Fax 114018 0
Email 114018 0
i.reid@auckland.ac.nz
Contact person for public queries
Name 114019 0
Prof Ian Reid
Address 114019 0
The University of Auckland
Private Bag 92019
Auckland 1142
Country 114019 0
New Zealand
Phone 114019 0
+64 21855160
Fax 114019 0
Email 114019 0
i.reid@auckland.ac.nz
Contact person for scientific queries
Name 114020 0
Prof Ian Reid
Address 114020 0
The University of Auckland
Private Bag 92019
Auckland 1142
Country 114020 0
New Zealand
Phone 114020 0
+64 21855160
Fax 114020 0
Email 114020 0
i.reid@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data sharing is not thought to be appropriate as this is a small, preliminary dose-find study which assesses only surrogate endpoints.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes IR Reid, J Wen, A Mellar, M Liu, A Jabr, AM Horne ... [More Details]
Plain language summaryNo Oral zoledronate 20 mg circumvents the problem of ... [More Details]

Documents added automatically
No additional documents have been identified.