Effect of Teriparatide Compared to Risedronate on Back Pain in Women With a Spine Fracture Caused by Osteoporosis

Study Overview
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Brief Summary
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The purpose of the study is to determine if daily teriparatide reduces back pain more effectively than weekly risedronate in women with osteoporosis who have chronic back pain due to a spinal bone fracture.

Official Title
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The Effect of Teriparatide Compared With Risedronate on Back Pain in Postmenopausal Women With Osteoporotic Vertebral Fractures

Conditions
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Osteoporosis, Postmenopausal, Back Pain, Spinal Fracture

Intervention / Treatment
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* Drug: teriparatide
* Drug: risedronate
* Drug: placebo
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women 45 years or older. No period for at least two years. History of back pain that started at least 2 months prior to the initial visit (likely due to spinal bone fracture determined by investigator). Minimum of one moderate spinal bone fracture. Beginning pain level of at least four on an eleven point scale. Bone Mineral Density (BMD) must meet criteria Able to read, understand, and administer self-questionnaires. Be willing and able to use a pen-injector to deliver the medication. Exclusion Criteria: Are at increased risk for osteosarcoma. Have an active or suspected diseases that affects bone metabolism other than osteoporosis. Participants that already know that they will require procedures to repair their spinal bone fractures. Abnormal values of certain lab tests. Anything that would make it difficult to determine if the back pain was due to the fracture. Poor medical or psychiatric condition. Alcohol or drug abuse within a year of the study start. Certain malignant neoplasms in the 5 years prior to enrollment. Active liver disease or clinical jaundice. Significantly impaired renal function. History of nephrolithiasis or urolithiasis within 2 years prior to enrollment. Known contraindication or intolerance to risedronate and/or teriparatide therapy. Treatment with oral strontium or certain therapeutic doses of fluoride.

Ages Eligible for Study
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Minimum Age: 45 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriparatide<br>Teriparatide 20 micrograms (ug)/day, subcutaneous, 18 months plus once weekly oral placebo | Drug: teriparatide<br>* 20 ug/day, subcutaneous, 18 months<br>* Other names: Forsteo;Drug: placebo<br>* once weekly, oral, 18 months<br>* Other names: Forsteo;|
| Active Comparator: Risedronate<br>Risedronate 35 milligrams (mg)/once weekly, oral, 18 months plus daily subcutaneous injection placebo | Drug: risedronate<br>* 35 mg/once weekly, oral, 18 months<br>* Other names: Actonel;Drug: placebo<br>* daily, subcutaneous, 18 months<br>* Other names: Actonel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Responding With at Least a 30% Reduction in 24-Hour Worst Back Pain Severity at the 6-Month Endpoint | 24-hour worst back pain severity scores recorded daily on an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The 11-point scale is used for assessment of worst back pain in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. Responders are defined as participants with at least a 30% reduction in the severity of worst back pain from baseline to the 6-month last observation carried forward (LOCF) endpoint. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Responding With at Least a 30% Reduction in 24-Hour Worst Back Pain Severity at the 12-Month Endpoint | 24-hour worst back pain severity scores recorded daily on an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The 11-point scale is used for assessment of worst back pain in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. Responders are defined as participants with at least a 30% reduction in the severity of worst back pain from baseline to the 12-month last observation carried forward (LOCF) endpoint. | 12 Months | 
| Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 6-Month Endpoint | 24-hour average back pain severity scores recorded daily on an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The 11-point scale is used for assessment of average back pain in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. Responders are defined as participants with at least a 30% reduction in the severity of average back pain from baseline to the 6-month last observation carried forward (LOCF) endpoint. | 6 Months | 
| Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 12-Month Endpoint | 24-hour average back pain severity scores recorded daily on an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The 11-point scale is used for assessment of average back pain in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. Responders are defined as participants with at least a 30% reduction in the severity of average back pain from baseline to the 12-month last observation carried forward (LOCF) endpoint. | 12 Months | 
| Number of Participants With Time to First Occurrence of at Least 30% Reduction in 24-Hour Worst Back Pain up to 6 Months | Time to first occurrence of >= 30% pain reduction in worst back pain from baseline to 6 months. Worst back pain is assessed using an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain), to rate the worst back pain experienced in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. The results are reported as the number of participants reporting at least a 30% reduction in the severity of worst back pain up to time (t) in days. | Days 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, and 300 | 
| Number of Participants With Time to First Occurrence of at Least 30% Reduction in 24-Hour Worst Back Pain up to 12 Months | Time to first occurrence of >= 30% pain reduction in worst back pain from baseline to 12 months. Worst back pain is assessed using an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain), to rate the worst back pain experienced in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. The results are reported as the number of participants reporting at least a 30% reduction in the severity of worst back pain up to time (t) in days. | Days 0, 60, 120, 180, 240, 300, 360, 420, 480, 540, and 600 | 
| Number of Participants With Time to First Occurrence of at Least a 30% Reduction in 24-Hour Average Back Pain up to 6 Months | Time to first occurrence of >=30% pain reduction in average back pain from baseline to 6 months. Average back pain is assessed using an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain), to rate the average back pain experienced in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. The results are reported as the number of participants reporting at least a 30% reduction in the severity of average back pain up to time (t) in days. | Days 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, and 300 | 
| Number of Participants With Time to First Occurrence of at Least a 30% Reduction in 24-Hour Average Back Pain up to 12 Months | Time to first occurrence of >= 30% pain reduction in average back pain from baseline to 12 months. Average back pain is assessed using an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain), to rate the average back pain experienced in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. The results are reported as the number of participants reporting at least a 30% reduction in the severity of average back pain up to time (t) in days. | Days 0, 60, 120, 180, 240, 300, 360, 420, 480, 540, and 600 | 
| Change From Baseline to 3-Month Endpoint in the Roland-Morris Disability Questionnaire. | Roland-Morris Disability Questionnaire (RMDQ-24) is completed by the participant and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician and a total score is given. The total score ranges from 0 (no disability) to 24 (severe disability). | Baseline, 3 Months | 
| Change From Baseline to 6-Month Endpoint in the Roland-Morris Disability Questionnaire. | Roland-Morris Disability Questionnaire (RMDQ-24) is completed by the participant and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician and a total score is given. The total score ranges from 0 (no disability) to 24 (severe disability). | Baseline, 6 Months | 
| Change From Baseline to 12-Month Endpoint in the Roland-Morris Disability Questionnaire. | Roland-Morris Disability Questionnaire (RMDQ-24) is completed by the participant and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician and a total score is given. The total score ranges from 0 (no disability) to 24 (severe disability). | Baseline, 12 Months | 
| Change From Baseline to 6-Month Endpoint, European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO) | QUALEFFO is an osteoporosis-specific health instrument developed specifically for participants with vertebral deformities used to evaluate the effect of back pain and treatment on quality of life. The QUALEFFO questionnaire includes 41 items in 5 domains: pain, physical function, social function, general health perception, and mental function. The total score is calculated according to the scoring algorithm developed by the International Osteoporosis Foundation. Total scores are reported from 0 to 100, with lower scores corresponding to better quality of life. | Baseline, 6 Months | 
| Change From Baseline to 12-Month Endpoint, European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO) | QUALEFFO is an osteoporosis-specific health instrument developed specifically for participants with vertebral deformities used to evaluate the effect of back pain and treatment on quality of life. The QUALEFFO questionnaire includes 41 items in 5 domains: pain, physical function, social function, general health perception, and mental function. The total score is calculated according to the scoring algorithm developed by the International Osteoporosis Foundation. Total scores are reported from 0 to 100, with lower scores corresponding to better quality of life. | Baseline, 12 Months | 
| Number of Participants With Adverse Events (Safety) During 12 Months | Safety was assessed via serious adverse events and all other non-serious adverse events and the data are located in the Reported Adverse Events Section. | Baseline through 12 Months | 
| Number of Participants With Adverse Events (Safety) During 18 Months | Safety is assessed via serious adverse events and all other non-serious adverse events and the data are located in the Reported Adverse Events Section. | Baseline through 18 Months | 
| Number of Participants Responding With at Least a 30% Reduction in 24-Hour Worst Back Pain Severity at the 18-Month Endpoint | 24-hour worst back pain severity scores recorded daily on an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The 11-point scale is used for assessment of worst back pain in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. Responders are defined as participants with at least a 30% reduction in the severity of worst back pain from baseline to the 18-month last observation carried forward (LOCF) endpoint. | 18 Months | 
| Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 18-Month Endpoint | 24-hour average back pain severity scores recorded daily on an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). The 11-point scale is used for assessment of average back pain in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. Responders are defined as participants with at least a 30% reduction in the severity of average back pain from baseline to the 18-month last observation carried forward (LOCF) endpoint. | 18 Months | 
| Number of Participants With Time to First Occurrence of at Least 30% Reduction in 24-Hour Worst Back Pain up to 18 Months | Time to first occurrence of >= 30% pain reduction in worst back pain from baseline to 18 months. Worst back pain is assessed using an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain), to rate the worst back pain experienced in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. The results are reported as the number of participants reporting at least a 30% reduction in the severity of worst back pain up to time (t) in days. | Baseline through 18 Months | 
| Number of Participants With Time to First Occurrence of at Least a 30% Reduction in 24-Hour Average Back Pain up to 18 Months | Time to first occurrence of >=30% pain reduction in average back pain from baseline to 18 months. Average back pain is assessed using an 11-point numeric rating scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain), to rate the average back pain experienced in the preceding 24 hours and is evaluated daily in the week prior to each scheduled study visit. The results are reported as the number of participants reporting at least a 30% reduction in the severity of average back pain up to time (t) in days. | Baseline through 18 Months | 
| Change From Baseline to 18-Month Endpoint in the Roland-Morris Disability Questionnaire. | Roland-Morris Disability Questionnaire (RMDQ-24) is completed by the participant and measures the degree of disability due to back pain. The questionnaire consists of 24 statements and the participant is instructed to put a mark next to each appropriate statement. The number of statements marked are added up by the clinician and a total score is given. The total score ranges from 0 (no disability) to 24 (severe disability). Pooled site, baseline glucocorticoid usage status (yes/no) and baseline score were controlled for. | Baseline, 18 Months | 
| Change From Baseline to 18-Month Endpoint in European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO) | QUALEFFO is an osteoporosis-specific health instrument developed specifically for participants with vertebral deformities used to evaluate the effect of back pain and treatment on quality of life. The QUALEFFO questionnaire includes 41 items in 5 domains: pain, physical function, social function, general health perception, and mental function. The total score is calculated according to the scoring algorithm developed by the International Osteoporosis Foundation. Total scores are reported from 0 to 100, with lower scores corresponding to better quality of life. | Baseline, 18 Months |