A Study for the Transdermal Application of Teriparatide

This study has been completed.
Sponsor:
Collaborator:
TransPharma Medical
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01011556
First received: November 9, 2009
Last updated: September 21, 2012
Last verified: September 2012
  Purpose

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.

Condition Intervention Phase
Osteoporosis
Drug: Subcutaneous Teriparatide
Drug: Transdermal Teriparatide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Study for Transdermal Application of Teriparatide

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months [ Time Frame: Baseline, 12 Months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 6 Months [ Time Frame: Baseline, 6 Months ] [ Designated as safety issue: No ]
    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.

  • Time Course Change of BMD Response at the Lumbar Spine [ Time Frame: Baseline to 6 Months and 12 Months ] [ Designated as safety issue: No ]
    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).

  • Percent Change From Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) [ Time Frame: Baseline, 1 Month, 3 Months, 6 Months, 12 Months ] [ Designated as safety issue: No ]
    Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation.

  • Percent Change From Baseline of C-Terminal Telopeptide (CTX) [ Time Frame: Baseline, 1 Month, 3 Months, 6 Months, 12 Months ] [ Designated as safety issue: No ]
    C-terminal telopeptide is a marker of bone resorption.

  • Percent Change From Baseline in Serum Procollagen Type 1 C-Propeptide (P1CP) at 1 Month [ Time Frame: Baseline, 1 Month ] [ Designated as safety issue: No ]
    Procollagen Type 1 N-Terminal Propeptide (P1NP) is a marker of bone formation.

  • Convenience/Ease of Use Questionnaire (CEUQ) [ Time Frame: baseline up to 12 months ] [ Designated as safety issue: No ]
    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.

  • Change in Serum Calcium With and Without Adjustments for Serum Albumin From Predose to After 4 and 6 Hours [ Time Frame: Baseline, 12 Months ] [ Designated as safety issue: Yes ]
    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).

  • Change From Baseline in Urine Calcium Excretion at 6 and 12 Months [ Time Frame: Baseline, 6 Months, 12 Months ] [ Designated as safety issue: Yes ]
  • Change From Pre-dose and Postdose Supine and Standing SBP and DBP at Baseline (BL) and 12 Months (Mon) [ Time Frame: Pre-Dose, 30 minutes, 2 hours Post-Dose at Baseline and 12 Months ] [ Designated as safety issue: Yes ]
    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.

  • Change From Pre-dose to Postdose in Supine and Standing Heart Rate at Baseline (BL) and 12 Months (Mon). [ Time Frame: Pre-dose, 30 minutes, 2 hours at Baseline and 12 Months ] [ Designated as safety issue: Yes ]
  • Number of Participants With Parathyroid Hormone (PTH) Specific Antibody Levels [ Time Frame: Baseline and 1, 3, 12, and 13 Months (mon) ] [ Designated as safety issue: No ]
    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).

  • Pharmacokinetics Parameters: Area Under the Curve (AUC) [ Time Frame: Baseline, 1 Month, 3 Months, and 12 Months ] [ Designated as safety issue: No ]
    Due to high intra-subject variability, data was not analyzed for this outcome measure.

  • Pharmacokinetics Parameters: Maximal Concentration (Cmax) [ Time Frame: Baseline, 1 Month, 3 Months, 12 Months ] [ Designated as safety issue: No ]
    Due to high intra-subject variability, data was not analyzed for this outcome measure.

  • DRAIZE Edema Assessment at Baseline Through 13 Month Follow-up [ Time Frame: 13 Month follow-up ] [ Designated as safety issue: Yes ]
    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)

  • DRAIZE Erythema Assessment at Baseline Through 13 Month Follow-up [ Time Frame: 13 Month follow-up ] [ Designated as safety issue: Yes ]
    Severity of erythema was categorized based on a 5 point scale: 0=no erythema, 4=severe erythema (defined as beet red to eschar)


Enrollment: 233
Study Start Date: November 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 20 mcg Subcutaneous Teriparatide
Received 20 micrograms (mcg) subcutaneously once daily in an unblinded manner.
Drug: Subcutaneous Teriparatide
Administered subcutaneously once daily for 12 months
Other Names:
  • recombinant human parathyroid hormone (rhPTH) (1-34)
  • recombinant human teriparatide
  • Forteo
  • Forsteo
  • LY333334
Experimental: 30 mcg Transdermal Teriparatide
Received 30 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Drug: Transdermal Teriparatide
Administered transdermally, applied once daily for 6 hours over 12 months
Other Names:
  • synthetic human parathyroid hormone (shPTH) (1-34)
  • synthetic human teriparatide
Experimental: 50 mcg Transdermal Teriparatide
Received 50 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Drug: Transdermal Teriparatide
Administered transdermally, applied once daily for 6 hours over 12 months
Other Names:
  • synthetic human parathyroid hormone (shPTH) (1-34)
  • synthetic human teriparatide
Experimental: 80 mcg Transdermal Teriparatide
Received 80 micrograms (mcg) teriparatide transdermally via a patch applied once daily. Participants were blinded to dose level.
Drug: Transdermal Teriparatide
Administered transdermally, applied once daily for 6 hours over 12 months
Other Names:
  • synthetic human parathyroid hormone (shPTH) (1-34)
  • synthetic human teriparatide

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011556

Locations
Argentina
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Buenos Aires, Argentina, C1128AAF
Estonia
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Parnu, Estonia, 80010
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Tallin, Estonia, 10138
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Tartu, Estonia, 50410
Hungary
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Balatonfured, Hungary, 8230
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Budapest, Hungary, 1036
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Debrecen, Hungary, 4043
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Esztergom, Hungary, 2500
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Gyor, Hungary, 9023
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Szombathely, Hungary, H-9700
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Tatabanya, Hungary, 2800
Mexico
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Guadalajara, Mexico, 44158
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mexico City, Mexico, 03300
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Monterrey, Mexico, 64460
Romania
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bucharest, Romania, 011025
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Cluj-Napoca, Romania, 400006
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Lasi, Romania, 700111
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Timisoara, Romania, 300736
Sponsors and Collaborators
Eli Lilly and Company
TransPharma Medical
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01011556     History of Changes
Other Study ID Numbers: 12641, I2Y-MC-GHFA(c)
Study First Received: November 9, 2009
Results First Received: September 21, 2012
Last Updated: September 21, 2012
Health Authority: Hungary: National Institute of Pharmacy
Estonia: The State Agency of Medicine
Romania: National Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by Eli Lilly and Company:
Age Related Osteoporosis
Senile Osteoporosis

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Teriparatide
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014