A Multiple-Dose Study to Evaluate Skin Irritation and Sensitization of Teriparatide Administered Transdermally in Healthy Postmenopausal Women
Condition: Osteoporosis, Postmenopausal
MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal
Intervention: LY333334; Placebo
Intervention description: Transdermal patch; Transdermal patch
Intervention MeSH terms: Teriparatide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Enrollment: 251.0
Sex: Female
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study is a Phase 1, multi-center, 2-part, subject- and investigator-blind, randomized,
      placebo-controlled, multiple dose study of transdermal teriparatide (80-µg dose) in healthy
      postmenopausal women. Part A will examine the cumulative irritation and adherence of the
      transdermal patch, and Part B will examine skin sensitization and adherence. Two separate
      groups of subjects will be enrolled for Part A and Part B of the study. All screening
      procedures will take place up to 28 days prior to enrollment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are overtly healthy postmenopausal females, as determined by medical history, physical
             examination, vital signs, electrocardiogram (ECG), and laboratory tests (for example,
             subjects who have osteoporosis or stable and/or controlled hyperlipidemia,
             hypertension, and/or hypothyroidism may be entered if that investigator judges it
             appropriate for participation in this study).

          -  Postmenopausal women include women with at least 6-weeks postsurgical bilateral
             oophorectomy with or without hysterectomy, confirmed by medical history, or
             spontaneous amenorrhea for at least 6 to 12 months, not induced by a medical condition
             such as anorexia nervosa and not taking medications during the amenorrhea that induced
             the amenorrhea (eg, oral contraceptives, hormones, gonadotropin-releasing hormone,
             anti-estrogens, selective estrogen receptor modulators, or chemotherapy) and a
             follicle-stimulating hormone level greater than 40 mIU/mL.

          -  Have clinical laboratory test results within normal reference range for the population
             or investigator site, or results with acceptable deviations that are judged to be not
             clinically significant by the investigator.

          -  Have a sitting blood pressure and pulse rate that are judged to be not clinically
             significant by the investigator.

          -  Are reliable and willing to make themselves available for the duration of the study
             and are willing to follow study procedures.

          -  Have given written informed consent approved by Eli Lilly and Company (Lilly) and the
             ethical review board (ERB) governing the site.

        Exclusion Criteria:

          -  Are currently enrolled in, or discontinued within the last 3 months from, a clinical
             trial involving an investigational drug or device or off-label use of a drug or
             device, or are concurrently enrolled in any other type of medical research judged not
             to be scientifically or medically compatible with this study.

          -  Have known hypersensitivity to teriparatide or to any of its excipients.

          -  Are persons who have previously completed or withdrawn from this study or any other
             study investigating teriparatide patch.

          -  Have an abnormality in the 12-lead ECG that, in the opinion of the investigator,
             increases the risks associated with participating in the study.

          -  Have a history or presence of cardiovascular, respiratory, hepatic, renal,
             gastrointestinal, endocrine, hematological, or neurological disorders capable of
             significantly altering the absorption, metabolism, or elimination of drugs; of
             constituting a risk when taking the study medication; or of interfering with the
             interpretation of data.

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening.

          -  Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV
             antibodies.

          -  Show evidence of hepatitis C and/or positive hepatitis C antibody.

          -  Show evidence of hepatitis B and/or positive hepatitis B surface antigen.

          -  Have a history of breast cancer within the past 10 years or other types of carcinoma
             within the past 5 years, except for excised superficial skin tumors and adequately
             treated in situ carcinoma of cervix.

          -  Have an average weekly alcohol intake that exceeds 14 units per week,

             (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of
             distilled spirits).

          -  Have hyperparathyroidism or hypoparathyroidism.

          -  Have hyperthyroidism.

          -  Have hypercalciuria (24-hour collection above 300 mg/day).

          -  Have hypercalcemia (above the upper limit of reference range).

          -  Have a history of bone diseases such as Paget's disease of bone, bone carcinoma, bone
             metastases, metabolic bone disease other than osteoporosis, or unexplained elevation
             in serum alkaline phosphatase level.

          -  Have a history of external beam or implant radiation involving the skeleton.

          -  Have a history of recurrent nephrolithiasis, or a single episode within the past 5
             years. Eligible subjects who have had an episode within the past 5 to 10 years must
             have a kidney-ureter-bladder X-ray of the abdominal area within 1 month prior to
             enrollment in the study, which indicates no existing stone.

          -  Have a history of bleeding disorder within the past 3 years.

          -  Are currently using therapies for osteoporosis; or using hormone replacement therapy
             or bisphosphonates during the previous 3 months. Women receiving short-term hormone
             therapy for the treatment of moderate to severe menopausal symptoms may be enrolled if
             their postmenopausal status is confirmed by inclusion criterion.

          -  Have presence of a dermatologic disease that might interfere with the evaluation of
             the test site reaction; and clinically significant scars, wounds, or discoloration, or
             abnormalities of the skin at or near the intended site of electrode application (for
             example, porphyria, atopy, psoriasis, vitiligo).

          -  Have a history of severe skin infection within the past year in the opinion of the
             investigator.

          -  Have a history of skin allergy or hypersensitivity to tapes or adhesives, in the
             opinion of the investigator.

          -  Have a history of significant dermatologic cancers (for example, melanoma, squamous
             cell carcinoma), except basal-cell carcinomas that were superficial and did not
             involve the investigative site.

          -  Have an obvious difference in skin color between arms or the presence of a skin
             condition, excessive hair at the application sites, scar tissue, tattoo, or coloration
             that would interfere with placement of test articles, skin assessment, or reactions to
             drug.

          -  Have implanted or externally mounted electrical or electronic medical devices (for
             example, pacemakers).

          -  Have used topical analgesics or topical corticosteroids within 3 weeks of study
             enrollment.

          -  Have taken antihistamines within 72 hours prior to dosing.

          -  Any other condition which, in the opinion of the investigator, would preclude
             participation in the study.