A Study for the Transdermal Application of Teriparatide

A Phase 2 Study for Transdermal Application of Teriparatide

The primary purpose of this study is to help answer the following research questions:

1. How teriparatide given using a skin patch (transferred through the skin using the ViaDerm Teriparatide System) compares to teriparatide injected under the skin with a needle (pen injector) affects your bone density (how solid or porous your bones are).
2. The safety of the teriparatide skin patch and any side effects that might be associated with it.

Teriparatide 20 micrograms (mcg) per day is currently only available as a subcutaneous (SQ) injection and many patients with severe osteoporosis for whom anabolic therapy with teriparatide is appropriate are either unwilling or physically unable to self-inject. The purpose of this Phase 2 study is to identify a transdermal dose or doses that will be comparable to the teriparatide 20 mcg SQ dose from a pharmacodynamic (PD) and safety standpoint for use in future Phase 3 studies.

Inclusion Criteria:

• Ambulatory, postmenopausal women.
• Centrally confirmed lumbar spine or femoral neck bone mineral density (BMD) T-score of less than or equal to -2.5.
• Without language barrier, cooperative, expected to return for all follow-up procedures, and have given informed consent after being informed of the risks, medications, and procedures to be used in the study.
• Able to use the pen-type injection delivery system and the ViaDerm Teriparatide System satisfactorily in the opinion of the investigator, or with the help of a family member or caregiver.
• Able to be reached by telephone for follow-up contact between visits

Exclusion Criteria:

• Abnormal laboratory values for albumin and alkaline phosphatase.
• Laboratory values outside the ranges defined in the protocol for the following: Serum calcium, intact parathyroid hormone (iPTH), 25 hydroxyvitamin D, and 24-hour urine calcium
• History of diseases other than postmenopausal osteoporosis that affect bone metabolism, such as Paget's disease, renal osteodystrophy, osteomalacia, any secondary causes of osteoporosis, hypoparathyroidism, hyperparathyroidism, and intestinal malabsorption.
• History of malignant neoplasms in the 5 years prior to randomization, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitively treated. Patients with carcinoma in situ of the uterine cervix treated definitively more than 1 year prior to entry into the study may be randomized.
• Use of a pacemaker.
• Known chronic dermatological disorder, such as contact dermatitis
• History of allergy or sensitivity to tapes or adhesives
• Patients prone to bleeding with coagulopathies, such as hemophilia or thrombocytopenia.
• Patients who have an increased baseline risk of osteosarcoma, Paget's disease of the bone, or unexplained elevations of alkaline phosphatase; or prior external beam, implant radiation therapy involving the skeleton, or previous primary skeletal malignancy.
• Major fracture within the past year in the femur, tibia, humerus, or radius (with or without ulna).

Treatment with:

• calcitonins in the 2 months prior to randomization.
• oral, transdermal/patch, or injectable estrogens, progestins, estrogen analogs, estrogen agonists, estrogen antagonists, selective estrogen receptor modulators, or tibolone in the 3 months prior to randomization; treatment with intravaginal estrogens in doses higher than 0.3 mg of conjugated equine estrogen, or the equivalent, for more than 3 doses per week in the 3 months prior to randomization.
• androgens or other anabolic steroids in the 6 months prior to randomization.
• fluorides in the 2 years prior to randomization. (Previous or current use of fluoridated water or topical dental fluoride treatments are permitted.)
• oral bisphosphonates for more than 2 consecutive months in the 6 months prior to randomization; treatment with intravenous bisphosphonates in the 6 months prior to randomization; treatment with more than 1 cycle of intermittent oral bisphosphonates in the 6 months prior to randomization; or having received the last cycle of this intermittent oral regimen less than 4 weeks prior to screening.
• patients receiving intravenous zoledronic acid during the 12 months prior to randomization.
• vitamin D greater than 50,000 International Units (IU) per week or with any dose of calcitriol or vitamin D analogs or agonists in the 6 months prior to randomization.
• systemic corticosteroids in the 1 month prior to randomization or for more than 30 days in the 1 year prior to randomization. (Ophthalmic, otic, topical, orally inhaled, nasally inhaled, or intra-articular corticosteroid therapy may be used without these restrictions.)
• any other drug known to significantly affect bone metabolism in the 6 months prior to randomization.
• warfarin or other coumadin anticoagulants in the 1 month prior to randomization.
• any investigational drug in the 1 month prior to entry into the study.