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Trial registered on ANZCTR


Registration number
ACTRN12615000195550
Ethics application status
Approved
Date submitted
30/01/2015
Date registered
2/03/2015
Date last updated
24/07/2019
Date data sharing statement initially provided
24/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 2a Open Label Study to Evaluate the Pharmacokinetics and Safety of Parathyroid Hormone hPTH(1-34) Administered via Transdermal Delivery and Subcutaneous Injection [Forteo Registered Trademark (teriparatide)] in Healthy Postmenopausal Women
Scientific title
A Phase 2a Open Label Study to Evaluate the Pharmacokinetics and Safety of Parathyroid Hormone hPTH(1-34) Administered via Transdermal Delivery and Subcutaneous Injection [Forteo Registered Trademark (teriparatide)] in Healthy Postmenopausal Women
Secondary ID [1] 285870 0
Nil known
Universal Trial Number (UTN)
U1111-1165-3007
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 293785 0
Condition category
Condition code
Musculoskeletal 294088 294088 0 0
Osteoporosis
Metabolic and Endocrine 294089 294089 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part A
Treatment A: MicroCor Registered Trademark hPTH(1-34) Transdermal System (TDS) 16 mcg single day application, consecutive day cross over
Treatment B: MicroCor Registered Trademark hPTH(1-34)
TDS 38 mcg single day application, consecutive day cross over
Treatment C: Forteo Registered Trademark teriparatide (rDNA origin) 20 mcg; single subcutaneous injection
Treatment E: MicroCor Registered Trademark hPTH(1-34) Transdermal System model 2 (TDS) 38 mcg single day application, consecutive day cross over. Proprietary internal mechanical design differs between TDS and TDS Model 2.

Part B
Treatment B: MicroCor Registered Trademark hPTH(1-34)
Transdermal System (TDS) 38 mcg daily application for 28 days
Treatment C: Forteo Registered Trademark teriparatide (rDNA origin) 20 mcg subcutaneous injection daily for 28 days.
Treatment B subjects will have Treatment D MicroCor Registered Trademark placebo Transdermal System (TDS) applied concurrently twice over the 28 days.

Part A participants will not be recruited into Part B. Subjects will complete a daily dosing diary that will be reviewed by the study staff to monitor adherence.
Intervention code [1] 290851 0
Treatment: Drugs
Intervention code [2] 290915 0
Treatment: Devices
Comparator / control treatment
MicroCor Registered Trademark placebo Transdermal System (TDS) will be applied to Treatment B participants concurrently on two days over the 28 day period in Part B.

Forteo Registered Trademark teriparatide (rDNA origin) 20 mcg subcutaneous injection will be used as the comparator.
Control group
Placebo

Outcomes
Primary outcome [1] 294051 0
Pharmacokinetic primary variables include: Cmax, AUC0-last, AUC0-8, and AUC0-tau. Assessed in plasma.
Timepoint [1] 294051 0
Part A: Pre-dose, and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 180, 240, 360 minutes after treatment administration.
Part B: Day 1 and Day 28 at Predose and 5, 10, 30, 60, 120, 240, 360 minutes after treatment.
Secondary outcome [1] 312419 0
Routine Blood chemistry for safety
Timepoint [1] 312419 0
Part A: Days 1-4, Day 7
Part B: Day 1, 2, 3 4, 5, 6, 7, 10, 12, 14, 17, 19, 21, 24, 26, 28, 42, Day
56
Secondary outcome [2] 312420 0
Any adverse event reported by subject and recorded in CRFs, for example new or worsened clinical conditions, clinically significant laboratory abnormalities; will be followed by study staff over their study participation (Part A 7 days; Part B 56 days. Any Serious Adverse Events will be followed and reported per industry guidance.
Timepoint [2] 312420 0
All study days in Part A (7 days) and Part B (56 days)
Secondary outcome [3] 312422 0
8 point Validated Local Irritation categorical scale
Timepoint [3] 312422 0
At the time of dosing, and at 2, 8, 24, 48 and 72 hours following removal of MicroCor units or completion of the Forteo Registered Trademark injection.
Secondary outcome [4] 312423 0
Anti- PTH antibody (Part B only) assessed by serum assay.
Timepoint [4] 312423 0
Pre-dose Day 1, Day 42, Day 56.
Secondary outcome [5] 312424 0
Pharmacokinetic: The secondary pharmacokinetic variables for comparison will include but is not limited to tmax, t1/2,Cmax, Cmin, Cavg, AUC, % Fluctuation, and Relative Bioavailability. Assessed by plasma assay.
Timepoint [5] 312424 0
Part A: Pre-dose, and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, 120, 180, 240, 360 minutes after treatment administration.
Part B: Day 1 and Day 28 at Predose and 5, 10, 30, 60, 120, 240, 360 minutes after treatment.
Secondary outcome [6] 312425 0
Pharmacodynamics: PINP, CTX and Osteocalcin parameters (for Part B only). Assessed in serum and plasma.
Timepoint [6] 312425 0
Days 1, 7, 14, 21, 28, 42, 56
Secondary outcome [7] 312426 0
Validated Adhesion scores
Timepoint [7] 312426 0
MicroCor hPTH(1-34) adhesion will be assessed immediately after
application, 1, 2, 3, 4, 5 minutes (+/-15 seconds).
Secondary outcome [8] 313047 0
Local discomfort by unpublished, proprietary measuring tool
Timepoint [8] 313047 0
On all dosing days immediately following activation of
MicroCor or injection of Forteo Registered Trademark, and immediately prior to TDS removal.
Secondary outcome [9] 313048 0
Applicator Performance: The plunger mechanism movement will be assessed by a Corium provided measuring unit.
Timepoint [9] 313048 0
Movement will be assessed in Part A on Day 7 with 3 consecutive measurements.

Eligibility
Key inclusion criteria
Inclusion:

Post-menopausal woman, aged 50-85 years old at screening in otherwise good general health as determined by the Investigator.

Agrees to being evaluated for baseline T scores or providing DXA results that are less than 1 year old or subject is
willing to undergo a DXA scan at the time of screening.

Must have no clinically significant findings as determined by the Investigator based on physical examination, 12-lead ECG and vital signs

Clinical laboratory values at screening, including ionized and total calcium, phosphorus, creatinine, albumin, and
PTH, must be within the normal limits as defined by the clinical laboratory, or are not clinically significant.

Corrected calcium (total calcium normalized) or albumin concentrations must be < upper limit of normal in ref range
at the screening visit.

25-hydroxyvitamin D must be >20 ng/ml at the screening visit.
Minimum age
50 Years
Maximum age
85 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion:

Has a diagnosis of osteoporosis, defined by bone mineral densitometry T score at any location on the body.

Had a loss of height greater than 5cm (2 inches) supported by medical records or subject self report.

Had recent bone fractures or fragility fractures.

Has an uncontrolled medical condition in the opinion of the Investigator or a controlled medical condition requiring
regular treatment with prescription drugs that would influence calcium, bone metabolism or relevant biomarkers.

Has history of significant chronic disease, cancer or any medical condition known to affect bone metabolism, hepatic or renal disorder requiring medical intervention.

Prior use of PTH replacement therapy or any of its analogs within the previous year.

Current use and/or use within the last year of corticosteroids (eye drops and topical creams are acceptable).

Currently use agents that influence calcium, bone metabolism or relevant biomarkers, such as calcitonins, bisphosphonates, Selective Estrogen Receptor Modulators (SERMs), teriparatide, phenobarbital, phenytoin,
glucocorticoids or anabolic steroid agents. Exceptions are: prior bisphosphate therapy if commenced one year prior to randomization, stable doses of Vitamin D and calcium supplements for at least three months prior to screening and PRN (as needed) use of anti-nausea medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The study is open-label (concealment is not carried out) with subject enrolment by age range; approximately 33% in 50-59 years old range and approximately 67% in 60-85 years old range. Subjects are randomised to treatment order in Part A and randomised to treatment allocation in Part B. For each study part, the master randomization schedule will be made of randomly permuted blocks of appropriate sizes, as determined by the statistician producing the master randomization schedules. A separate randomization schedule will be prepared for each study part. A separate randomization schedule will be produced for each age group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The study is open-label (concealment is not carried out) with subject enrolment by age range; approximately 33% in 50-59 years old range and approximately 67% in 60-85 years old range. Subjects are randomised to treatment order in Part A and randomised to treatment allocation in Part B. For each study part, the master randomization schedule will be made of randomly permuted blocks of appropriate sizes, as determined by the statistician producing the master randomization schedules. A separate randomization schedule will be prepared for each study part. A separate randomization schedule will be produced for each age group.
Phase
Phase 2
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/02/2015
Actual
16/02/2015
Date of last participant enrolment
Anticipated
Actual
7/07/2015
Date of last data collection
Anticipated
Actual
1/09/2015
Sample size
Target
39
Accrual to date
Final
41
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 9128 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 290588 0
Commercial sector/Industry
Name [1] 290588 0
Corium International, Inc
Country [1] 290588 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Corium International, Inc
Address
235 Constitution Drive
Menlo Park, CA 94025
Country
United States of America
Secondary sponsor category [1] 289278 0
None
Name [1] 289278 0
Address [1] 289278 0
Country [1] 289278 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292226 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 292226 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 292226 0
Australia
Date submitted for ethics approval [1] 292226 0
24/11/2014
Approval date [1] 292226 0
19/12/2014
Ethics approval number [1] 292226 0
525/14

Summary
Brief summary
Phase 2a open label, randomised study to evaluate the pharmacokinetics and safety of MicroCor hPTH(1-34) Administered via Transdermal Delivery and Subcutaneous Injection [Forteo Registered Trademark (teriparatide)] in healthy postmenopausal volunteers
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53626 0
Dr Jason Lickliter
Address 53626 0
Nucleus Network 5th Floor, Burnet Tower, AMREP
Precinct 89 Commercial Road Melbourne, Victoria, 3004
Country 53626 0
Australia
Phone 53626 0
+61 3 9076 8906
Fax 53626 0
+61 (0)3 9076 8911
Email 53626 0
[email protected]
Contact person for public queries
Name 53627 0
Vaeling Miller
Address 53627 0
Vaeling Miller, Senior Director of Clinical Operations
Corium International, Inc.
235 Constitution Drive
Menlo Park, CA 94025
Country 53627 0
United States of America
Phone 53627 0
+1 650-298-8255
Fax 53627 0
Email 53627 0
[email protected]
Contact person for scientific queries
Name 53628 0
Bobby Singh
Address 53628 0
Dr Bobby Singh, Vice President Research and Development
Corium International, Inc.
235 Constitution Drive
Menlo Park, CA 94025
Country 53628 0
United States of America
Phone 53628 0
+1 650-298-8255
Fax 53628 0
Email 53628 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AINon-invasive delivery strategies for biologics2018https://doi.org/10.1038/nrd.2018.183
EmbaseDissolving microneedles: Applications and growing therapeutic potential.2022https://dx.doi.org/10.1016/j.jconrel.2022.05.045
EmbaseA Narrative Review on Non-Invasive Drug Delivery of Teriparatide: A Ray of Hope.2023https://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2023045480
N.B. These documents automatically identified may not have been verified by the study sponsor.