| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| chronic back pain and osteoporotic vertebral fracture(s) |
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| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| to compare the efficacy of teriparatide 20 µg/day versus risedronate 35 mg/week on the reduction of back pain in postmenopausal women with prevalent osteoporotic vertebral fractures associated with chronic back pain. |
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| E.2.2 | Secondary objectives of the trial |
• Measure of pain score collected via daily diary during the 7 days prior to
each scheduled visit, the proportion of patients demonstrating at least a 30% reduction in severity of worst and average back pain from baseline to the following timepoints: 12 and 18 months, and 6, 12 and 18 moths respectively.
• Measure of pain score collected via daily diary during the 7 days prior to each scheduled visit, the time-to-first occurrence of a ≥30% reduction compared to the baseline pain score in worst and average back pain during 6, 12, and 18 months.
• Mean change in disability and quality of life:
o as assessed by the Roland Disability Questionnaire from baseline to the following timepoints: 3, 6, 12, and 18 months.
o as measured by the European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO) from baseline to the following timepoints: 6, 12, and 18 months.
• Adverse events.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
[1] Postmenopausal women 45 years of age and older 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 below the age of 55 years in whom a bilateral oophorectomy cannot clearly be documented must have their postmenopausal status confirmed by a serum follicle stimulating hormone level >30 IU/L and serum estradiol level <20 pg/ml or <73 pmol/L.
[2] History of back pain, despite conservative analgesic treatment, with back pain that started at least 2 months prior to Visit 1, that is likely to be caused by osteoporotic vertebral fracture(s) in the opinion of the investigator.
[3] A minimum of one moderate osteoporotic vertebral fracture not caused by severe trauma that is likely to be the cause of the back pain in the opinion of the investigator:
• A moderate vertebral fracture is defined as at least a 25% decrease in anterior, central, or posterior vertebral height (T4 to L4) as compared to the average height of adjacent vertebrae.
• Osteoporotic fracture is defined as a fracture not caused by a wound or injury that is severe enough to cause a fracture in otherwise healthy persons.
• The initial fracture assessment and the determination of eligibility of the patient to be entered into the study will be made by the individual investigator.
[4] Baseline pain score (mean score of the worst 24-hour pain intensity during the week prior to randomization) of at least 4 on the 11-point numeric rating scale.
[5] Lumbar spine or femoral neck or total hip BMD of 2.0 standard deviations or more below the average BMD for young, healthy, non-Hispanic, Caucasian women (T-score ≤-2.0). Table GHCY.1 presents the absolute values for assessing BMD at the lumbar spine, femoral neck, and total hip. If a BMD measure is not available from the 6 months prior to enrollment, then baseline BMD done prior to randomization must be performed locally, assessed by the investigator, and must meet the same BMD criteria as below.
[6] Able to read, understand, and respond to self-administered questionnaires.
[7] Without language barrier, cooperative, able to come to the clinic for all follow-up visits, and who has given informed consent before entering the study and after being informed of the medications and procedures to be used in this study.
[8] In the opinion of the investigator, the patient is willing to be trained and 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 care partner who has been trained to use the pen injector.
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| E.4 | Principal exclusion criteria |
[9] 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 skeletal alkaline phosphatase activity may indicate the presence of Paget’s disease, an unexplained elevation of this enzyme activity will also be exclusionary.
[10] Currently active or suspected diseases that affect bone metabolism, other than osteoporosis (such as renal osteodystrophy, osteomalacia, hyperparathyroidism, hypoparathyroidism, hyperthyroidism, sprue, inflammatory bowel disease, or malabsorption).
[11] Patients who are imminent candidates for kyphoplasty or vertebroplasty. Patients who require kyphoplasty or vertebroplasty after 6 months of treatment in this study will be allowed to continue in the study.
[12] Elevated serum calcium values, or abnormal serum thyroid-stimulating hormone, parathyroid hormone (PTH), or 25-hydroxyvitamin D levels, based on central laboratory reference ranges. Patients with minimal alterations of these labs may potentially be allowed in this study if there are no safety concerns, based on the opinion of both the investigator and the Lilly clinical research physician. Appropriate documentation of any such discussions is required.
[13] Clinical signs or symptoms, previous diagnostic imaging, lab test, or neurodiagnostic evidence of significant pathology which may be related to back pain and which would make interpretation of the back pain related to an osteoporotic vertebral fracture difficult or impossible, based on investigator assessment. Examples of such pathology would include (but are not limited to):
• radiculopathic/neuropathic pain due to nerve root compression of any cause
• significant spondylolisthesis, spinal stenosis, lateral recess stenosis
• spinal or paraspinal masses (such as tumors, metastases, angiomas, or abscesses)
• infectious or inflammatory processes of the spine or paraspinal region.
[14] Poor medical or psychiatric condition for participating in a clinical
study, in the opinion of the investigator.
[15] History of excessive consumption of alcohol or abuse of drugs in the 1 year prior to Visit 2, in the opinion of the investigator.
[16] 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. Subjects with carcinoma in situ of the uterine cervix treated definitively more than 1 year prior to entry into the study may be randomized. Patients with multiple myeloma or metastases to bone are excluded
[17] Active liver disease or clinical jaundice. Significantly impaired hepatic function, defined as ALT>75 U/L or GGT >300U/L.
[18] Significantly impaired renal function as defined by the following criteria:
• Significantly impaired renal function as defined as serum creatinine >2.0 mg/dL or 176.8 mmol/L.
[19] Patients with a history of nephrolithiasis or urolithiasis within 2 years prior to Visit 2.
[20] Patients with known contraindications to risedronate therapy or active or recent history of significant upper gastrointestinal disorders.
[21] Treatment with:
• oral strontium ranelate for any duration
• fluoride at therapeutic doses (≥20 mg/day) for more than 3 months during the last 2 years or for more than a total of 2 years, or any dosages within the 6 months prior to Visit 2 (previous or current use of fluoridated water or topical dental fluoride treatment is permitted).
[22] Prior participation in any other clinical trial studying PTH, teriparatide, or other PTH analogs; or prior treatment with PTH, teriparatide, or other PTH analogs.
[23] Have a known contraindication, intolerance, or allergy to teriparatide or risedronate, or to any diluents or excipients of teriparatide, or risedronate or is a poor candidate for teriparatide or risedronate therapy. (The investigator should refer to local product prescribing information).
[24] Have received treatment within the previous 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[25] Participation in any clinical studies involving drugs or indications not approved by the FDA at any time during their participation in this back pain study.
[26] Are investigator-site personnel directly affiliated with the study, or are immediate family of investigator-site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[27] Are employed by Lilly (that is, employees, temporary contract workers, or designees responsible for the conduct the study). Immediate family of Lilly employees may participate in Lilly-sponsored clinical studies. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary efficacy measure
proportion of patients treated with daily teriparatide compared with weekly risedronate who have at least a 30% improvement in the 11-point numeric rating scale (0=no pain; 10=worst pain imaginable) evaluating back pain from baseline to Month 6. Back pain severity will be assessed using an 11-point numeric rating scale to rate the worst back pain experienced in the preceding 24 hours, completed daily by patients during the week prior to each scheduled study visit. These scores will be recorded in a 7-day diary. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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