A Study for the Transdermal Application of Teriparatide

Study Overview
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Brief Summary
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The primary purpose of this study is to help answer the following research questions: 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). The safety of the teriparatide skin patch and any side effects that might be associated with it.

Detailed Description
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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.

Official Title
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A Phase 2 Study for Transdermal Application of Teriparatide

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Subcutaneous Teriparatide
* Drug: Transdermal Teriparatide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 20 mcg Subcutaneous Teriparatide<br>Received 20 micrograms (mcg) subcutaneously once daily in an unblinded manner. | Drug: Subcutaneous Teriparatide<br>* Administered subcutaneously once daily for 12 months<br>* Other names: LY333334;|
| Experimental: 30 mcg Transdermal Teriparatide<br>Received 30 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level. | Drug: Transdermal Teriparatide<br>* Administered transdermally, applied once daily for 6 hours over 12 months<br>* Other names: synthetic human teriparatide;|
| Experimental: 50 mcg Transdermal Teriparatide<br>Received 50 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level. | Drug: Transdermal Teriparatide<br>* Administered transdermally, applied once daily for 6 hours over 12 months<br>* Other names: synthetic human teriparatide;|
| Experimental: 80 mcg Transdermal Teriparatide<br>Received 80 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level. | Drug: Transdermal Teriparatide<br>* Administered transdermally, applied once daily for 6 hours over 12 months<br>* Other names: synthetic human teriparatide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | Bone mineral density (BMD) of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). Analyses were performed using ANCOVA model and least square (LS) means were adjusted for baseline BMD values as a covariate and pooled site and treatment as fixed effects. | Baseline, 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 6 Months | Bone mineral density (BMD) of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). Analyses were performed using ANCOVA model with the baseline value as a covariate and pooled site and treatment as fixed effects. | Baseline, 6 Months | 
| Time Course Change of BMD Response at the Lumbar Spine | To assess the time course of the treatment, the BMD data of the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA) and analyzed using a mixed model repeated measures (MMRM) method, with the repeated measure occurring at each visit (for example, 6 and 12 month). BMD values are corrected data and have been standardized across the machine types (Hologic and Lunar). | Baseline to 6 Months and 12 Months | 
| Percent Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) | Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation. | Baseline, 1 Month, 3 Months, 6 Months, 12 Months | 
| Percent Change From Baseline of C-Terminal Telopeptide (CTX) | C-terminal telopeptide is a marker of bone resorption. | Baseline, 1 Month, 3 Months, 6 Months, 12 Months | 
| Percent Change From Baseline in Serum Procollagen Type 1 C-Propeptide (P1CP) at 1 Month | Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation. | Baseline, 1 Month | 
| Convenience/Ease of Use Questionnaire (CEUQ) | CEUQ consists of 5 sections and 16 questions using a 5-point Likert scale designed to collect measures for ease of use (S1), convenience of use (S2), confidence of use (S3), fear of use (S4), and overall satisfaction with therapy (S5). CEUQ is not a validated instrument. | baseline up to 12 months | 
| Change in Serum Calcium With and Without Adjustments for Serum Albumin From Predose to After 4 and 6 Hours | Serum calcium adjusted for serum albumin levels is calculated using the following formula: Total Calcium + [(40 - albumin) x 0.02]. Analysis for serum calcium and albumin adjusted serum calcium were collected at predose, 4 hours (h) post-dose (PD) and 6 h PD at baseline and 12 months (mon). | Baseline, 12 Months | 
| Change From Baseline in Urine Calcium Excretion at 6 and 12 Months |  | Baseline, 6 Months, 12 Months | 
| Change From Pre-dose and Postdose Supine and Standing SBP and DBP at Baseline (BL) and 12 Months (Mon) | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) measured at pre-dose and 30 minutes (min) and 2 hours (hr) post-dose in both the supine and standing position. | Pre-Dose, 30 minutes, 2 hours Post-Dose at Baseline and 12 Months | 
| Change From Pre-dose to Postdose in Supine and Standing Heart Rate at Baseline (BL) and 12 Months (Mon). |  | Pre-dose, 30 minutes, 2 hours at Baseline and 12 Months | 
| Number of Participants With Parathyroid Hormone (PTH) Specific Antibody Levels | Participants were tested for anti-recombinant teriparatide and anti-synthetic teriparatide titers. Either none were detected (ND) or antibodies were determined to be present if the teriparatide specific antibody titers were at least 1:8 (titer 1:8). | Baseline and 1, 3, 12, and 13 Months (mon) | 
| Pharmacokinetics Parameters: Area Under the Curve (AUC) | Due to high intra-subject variability, data was not analyzed for this outcome measure. | Baseline, 1 Month, 3 Months, and 12 Months | 
| Pharmacokinetics Parameters: Maximal Concentration (Cmax) | Due to high intra-subject variability, data was not analyzed for this outcome measure. | Baseline, 1 Month, 3 Months, 12 Months | 
| DRAIZE Edema Assessment at Baseline Through 13 Month Follow-up | Severity of edema was categorized based on a 5 point scale: 0=no edema, 4=severe edema (defined as an area raised more than 1 millimeter and extending beyond area of exposure) | 13 Month follow-up | 
| DRAIZE Erythema Assessment at Baseline Through 13 Month Follow-up | Severity of erythema was categorized based on a 5 point scale: 0=no erythema, 4=severe erythema (defined as beet red to eschar) | 13 Month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age Related Osteoporosis, Senile Osteoporosis