A study in postmenopausal women with severe osteoporosis to compare the effects of two osteoporosis drugs (Teriparatide and Risedronate) on fractures of the spine

Phase 1

Conditions: Postmenopausal women with established osteoporosis and at least two moderate or one severe prevalent fragility fracture.
MedDRA version: 16.1Level: LLTClassification code 10031288Term: Osteoporosis with fractureSystem Organ Class: 100000004859
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2012-000123-41-PL

Lead Sponsor: Eli Lilly and Company Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 1340

Inclusion Criteria

Postmenopausal women = 45 years of age at the time of entry into the trial, whose last menstrual period occurred at least 2 years prior to entry into the trial, and are sufficiently mobile to complete study visits. Women < 55 years of age in whom a bilateral oophorectomy cannot clearly be documented must have their postmenopausal status confirmed by a serum FSH level > 40 IU/L and serum estradiol level < 20 pg/mL or < 73 pmol/L.

A minimum of 2 moderate (SQ2) or 1 severe (SQ3) vertebral fragility fractures, confirmed by the central reader.

AP lumbar spine, total hip or femoral neck BMD = 1.5 SD below the average BMD for young healthy, non-Hispanic, Caucasian women (T-score = –1.5 SD). Absolute BMD values will be applied to determine patient eligibility.

Without language barrier, cooperative, able to come to the clinic for all follow-up visits; has given informed consent before entering the study and after being informed of the medications and procedures to be used in this study.

In the opinion of the investigator, is willing to be trained and to use the pen injector daily, is able to satisfactorily use a pen-type injection delivery system, or is willing to receive daily subcutaneous injections from a caregiver who has been trained to use the pen injector.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Increased baseline risk of osteosarcoma. This includes patients with Paget’s disease of the bone, previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation. As elevation of serum alkaline phosphatase activity may indicate the presence of Paget’s disease, an unexplained elevation of this enzyme activity will also be exclusionary.

History of unresolved skeletal diseases that affect bone metabolism, other than osteoporosis, including renal osteodystrophy, osteomalacia, hyperparathyroidism (uncorrected), hypoparathyroidism, and intestinal malabsorption.

Abnormally elevated values of serum albumin-corrected calcium levels at baseline, defined as = 10.6 mg/dL (or = 2.65 mmol/L).

Abnormally low values of serum albumin- corrected calcium levels at baseline, defined as < 8.0 mg/dL (or < 2.0 mmol/L).

Abnormally elevated values of serum intact PTH(1-84) at baseline defined as > 72 pg/mL (or > 7.6 pmol/L).

Severe vitamin D deficiency at baseline defined as 25-hydroxy-vitamin D levels < 9.2 ng/mL (or < 23 nmol/L).

Abnormal thyroid function not corrected by therapy.

History of malignant neoplasms in the 5 years prior to Visit 2, with the exception of superficial basal cell or squamous cell carcinomas of the skin that have been definitively treated. Multiple myeloma or metastases to bone.

Active liver disease or clinical jaundice.

Significantly impaired hepatic or renal function.

History of nephrolithiasis or urolithiasis within 1 year prior to the randomization.

Considered imminent candidates for kyphoplasty or vertebroplasty before randomization.

Patients who have been treated with kyphoplasty or vertebroplasty at 3 or more levels before randomization.

Patients who have been treated with kyphoplasty or vertebroplasty within the last 6 months before randomization.

Patients with history of osteonecrosis of the jaw or who are, according to the clinical judgment of the investigator, at high risk to develop osteonecrosis of the jaw, including poor oral hygiene, scheduled invasive dental procedures, high doses of bisphosphonates and/or chemotherapy to treat malignancy.

Patients with history of atypical subtrochanteric or diaphyseal femoral fractures.

Active or recent history of significant upper gastrointestinal disorders, such as esophageal disorders which delay esophageal transit or emptying.

Unable to stand or sit in the upright position for at least 30 minutes.

Prior treatment with PTH, teriparatide, or other PTH analogs; or prior participation in any other clinical trial studying PTH, teriparatide, or other PTH analogs.

Previous treatment with the following bone active drugs is allowed but treatment must be discontinued at Visit 1 or at the time indicated below:
- oral bisphosphonates (including including alendronate, risedronate, ibandronate, etidronate). SERMs, calcitonin, estrogen (oral, transdermal, or injectable), progestin, estrogen analog, estrogen agonist, estrogen antagonist or tibolone, androgens, strontium ranelate, or active vitamin D3 analogues.
- Intravenous zoledronate, if the last dose was administered at least 12 months before Visit 1.
- Intravenous ibandronate or pamidronate, if the last dose was
administered at least 3 months before Visit 1.
- Subcutaneous denosumab, if the last dose was administered at least 6 months before Visit 1.
- Fluoride unless given at therapeutic doses (> 20 mg/day) for more than 3 months in the 2 years prio

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate if teriparatide 20 µg subcutaneously once daily is superior in reducing the incidence of new vertebral fractures during 24 months of therapy, when compared with risedronate 35 mg orally once weekly, in postmenopausal women with prevalent vertebral fragility fractures.;Secondary Objective: The key secondary objectives of this study are to evaluate if teriparatide 20 µg/day is superior in reducing the incidence of the following key outcomes during 24 months of therapy, when compared with risedronate 35 mg/week:<br><br>1. Incidence of pooled new and worsening vertebral fractures.<br>2. Incidence of pooled clinical fractures.<br>3. Incidence of non-vertebral fragility fractures.<br>4. Incidence of major non-vertebral fragility fractures: hip, radius, humerus, ribs, pelvis and ankle.;Primary end point(s): Incidence of new vertebral fractures;Timepoint(s) of evaluation of this end point: During the 24-month treatment phase

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key secondary fracture endpoints : <br><br>Incidence of pooled new and worsening vertebral fractures.<br>Incidence of pooled clinical fractures.<br>Incidence of non-vertebral fragility fractures.<br>Incidence of major non-vertebral fragility fractures: hip, radius, humerus, ribs, pelvis, and ankle.<br>;Timepoint(s) of evaluation of this end point: During the 24-month treatment phase

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