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

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12615000195550
• Date of registration: 02/03/2015
• Prospective Registration: No
• Primary sponsor: Corium International, Inc
• 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
• Date of first enrolment: 16/02/2015
• Target sample size: 39
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12615000195550.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Other;Type of endpoint: Pharmacokinetics;
• Phase: Phase 2

Countries of recruitment

Australia

Contacts

• Name: Ms Vaeling Miller

• Name: Dr Bobby Singh

Key inclusion & exclusion criteria

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.


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.


Age minimum: 50 Years
Age maximum: 85 Years
Gender: Females

Health Condition(s) or Problem(s) studied

Metabolic and Endocrine - Other metabolic disorders

Musculoskeletal - Osteoporosis

Osteoporosis;
Osteoporosis

Intervention(s)

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.

Primary Outcome(s)

Pharmacokinetic primary variables include: Cmax, AUC0-last, AUC0-8, and AUC0-tau. Assessed in plasma. [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(s)

8 point Validated Local Irritation categorical scale [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.]

Applicator Performance: The plunger mechanism movement will be assessed by a Corium provided measuring unit. [Movement will be assessed in Part A on Day 7 with 3 consecutive measurements.]

Local discomfort by unpublished, proprietary measuring tool[On all dosing days immediately following activation of
MicroCor or injection of Forteo Registered Trademark, and immediately prior to TDS removal.
]

Anti- PTH antibody (Part B only) assessed by serum assay. [Pre-dose Day 1, Day 42, Day 56.]

Routine Blood chemistry for safety[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]

Pharmacodynamics: PINP, CTX and Osteocalcin parameters (for Part B only). Assessed in serum and plasma. [Days 1, 7, 14, 21, 28, 42, 56]

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. [All study days in Part A (7 days) and Part B (56 days)]

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. [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. ]

Validated Adhesion scores [MicroCor hPTH(1-34) adhesion will be assessed immediately after
application, 1, 2, 3, 4, 5 minutes (+/-15 seconds).]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

Corium International, Inc

Ethics review

Status: Approved
Approval date:
Contact:

Alfred Hospital Ethics Committee