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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00343252
First received: June 20, 2006
Last updated: May 20, 2011
Last verified: May 2011
History of Changes
Results First Received: June 8, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Osteoporosis, Postmenopausal
Back Pain
Spinal Fracture
Interventions: Drug: teriparatide
Drug: risedronate
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
712 participants were randomized: 361 to teriparatide; 351 to risedronate. 2 participants did not receive drug. Only randomized participants who received at least 1 dose of drug were analyzed. At 18 months, reason for discontinuation was corrected from sponsor decision to entry criteria not met (1) and protocol violation (1) for 2 participants.

Reporting Groups
  Description
Teriparatide Teriparatide 20 micrograms (ug)/day, subcutaneous, 18 months plus once weekly oral placebo
Risedronate Risedronate 35 milligrams (mg)/once weekly, oral, 18 months plus daily subcutaneous injection placebo

Participant Flow for 4 periods

 Period 1:   All Randomized Participants
    Teriparatide     Risedronate  
STARTED     361     351  
COMPLETED     259     269  
NOT COMPLETED     102     82  

Period 2:   6 Months (All Treated Participants)
    Teriparatide     Risedronate  
STARTED     360 [1]   350 [2]
COMPLETED     304     306  
NOT COMPLETED     56     44  
Adverse Event                 17                 11  
Death                 0                 2  
Entry Criteria Not Met                 10                 8  
Lack of Efficacy                 0                 1  
Lost to Follow-up                 0                 4  
Physician Decision                 1                 3  
Protocol Violation                 2                 2  
Sponsor Decision                 7                 4  
Withdrawal by Subject                 19                 9  
[1] 361 participants were randomized but 1 did not receive study drug and was not analyzed.
[2] 351 participants were randomized but 1 did not receive study drug and was not analyzed.

Period 3:   12 Months (All Treated Participants)
    Teriparatide     Risedronate  
STARTED     360 [1]   350 [2]
COMPLETED     274 [3]   281 [3]
NOT COMPLETED     86     69  
Adverse Event                 22                 20  
Death                 3                 3  
Entry Criteria Not Met                 10                 10  
Lack of Efficacy                 1                 1  
Lost to Follow-up                 1                 5  
Physician Decision                 4                 5  
Protocol Violation                 3                 2  
Sponsor Decision                 9                 6  
Withdrawal by Subject                 33                 17  
[1] 361 participants were randomized but 1 did not receive study drug and was not analyzed.
[2] 351 participants were randomized but 1 did not receive study drug and was not analyzed.
[3] Completed 12 Months.

Period 4:   18 Months (All Treated Participants)
    Teriparatide     Risedronate  
STARTED     360     350  
COMPLETED     259     269  
NOT COMPLETED     101     81  
Adverse Event                 31                 23  
Death                 4                 5  
Entry Criteria Not Met                 11                 10  
Lack of Efficacy                 1                 1  
Lost to Follow-up                 3                 7  
Physician Decision                 4                 7  
Protocol Violation                 3                 3  
Sponsor Decision                 8                 5  
Withdrawal by Subject                 36                 20  



  Baseline Characteristics
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Reporting Groups
  Description
Teriparatide Teriparatide 20 micrograms (ug)/day, subcutaneous, 18 months plus once weekly oral placebo
Risedronate Risedronate 35 milligrams (mg)/once weekly, oral, 18 months plus daily subcutaneous injection placebo
Total Total of all reporting groups

Baseline Measures
    Teriparatide     Risedronate     Total  
Number of Participants  
[units: participants]
 		  360     350     710  
Age  
[units: years]
Mean ± Standard Deviation 		  70.54  ± 8.80     71.55  ± 8.12     71.04  ± 8.48  
Gender  
[units: participants]
 		     
Female     360     350     710  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
 		     
Hispanic     67     61     128  
African Descent     2     3     5  
Caucasian     285     286     571  
East Asian     3     0     3  
Native American     3     0     3  
Region of Enrollment  
[units: participants]
 		     
United States     50     48     98  
Argentina     38     42     80  
Australia     30     30     60  
Belgium     7     6     13  
Brazil     30     30     60  
Canada     54     55     109  
France     13     10     23  
Italy     22     20     42  
Mexico     23     23     46  
Puerto Rico     12     10     22  
Spain     32     32     64  
Sweden     13     10     23  
Germany     36     34     70  
Number of Vertebral Fractures [1]
[units: participants]
 		     
Unknown or No Vertebral Fractures     37     35     72  
1 Vertebral Fracture     126     104     230  
>=2 Vertebral Fractures     197     211     408  
Prior Osteoporosis Drug Use [2]
[units: participants]
 		     
Yes     267     258     525  
No     93     92     185  
Severity of Vertebral Fracture [3]
[units: participants]
 		     
Zero or Mild Severity (Grade 0)     50     46     96  
Moderate Severity (Grade 2)     160     166     326  
Severe (Grade 3)     142     131     273  
Unknown or Not Reported     8     7     15  
Spinal Deformity Index [4]
[units: units on a scale]
 		     
0     29     28     57  
1     11     16     27  
2     76     67     143  
>=3     236     232     468  
Unknown or Not Reported     8     7     15  
24-Hour Average Back Pain Score [5]
[units: units on a scale]
Mean ± Standard Deviation 		  5.34  ± 1.86     5.40  ± 1.85     5.37  ± 1.85  
24-Hour Worst Back Pain Score [6]
[units: units on a scale]
Mean ± Standard Deviation 		  6.80  ± 1.63     6.91  ± 1.54     6.85  ± 1.59  
Body Mass Index [7]
[units: kilograms/meters squared]
Mean ± Standard Deviation 		  26.30  ± 5.01     26.36  ± 4.91     26.33  ± 4.96  
Duration of Back Pain  
[units: days]
Mean ± Standard Deviation 		  550.33  ± 918.18     550.88  ± 750.47     550.58  ± 842.78  
Height  
[units: centimeters]
Mean ± Standard Deviation 		  154.82  ± 7.41     153.62  ± 7.86     154.23  ± 7.66  
Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) Score [8]
[units: units on a scale]
Mean ± Standard Deviation 		  47.08  ± 14.61     46.98  ± 14.39     47.03  ± 14.49  
Roland-Morris Disability Questionnaire Score [9]
[units: units on a scale]
Mean ± Standard Deviation 		  11.88  ± 5.47     12.12  ± 5.40     12.00  ± 5.44  
Weight  
[units: kilograms]
Mean ± Standard Deviation 		  63.02  ± 12.70     62.27  ± 12.58     62.65  ± 12.63  
[1] A minimum of at least one moderate osteoporotic vertebral fracture was radiologically detected and vertebral fracture status was documented. A moderate vertebral fracture was 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. This measure categorizes the number of vertebral fractures for each participant.
[2] Participants answered yes or no regarding use of osteoporosis drugs prior to this study.
[3] An experienced radiologist graded all vertebrae by visual inspection from normal (grade 0) to severely deformed (grade 3).
[4] Spinal deformity index is the summation of the severity of the vertebral fracture(s).
[5] 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 specified last observation carried forward (LOCF) endpoint.
[6] 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.
[7] Body mass index is an estimate of body fat based on body weight divided by height squared.
[8] 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.
[9] 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 is added up by the clinician and a total score is given. The total score ranges from 0 (no disability) to 24 (severe disability).



  Outcome Measures
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1.  Primary:   Number of Participants Responding With at Least a 30% Reduction in 24-Hour Worst Back Pain Severity at the 6-Month Endpoint   [ Time Frame: 6 Months ]
  Show Outcome Measure 1

2.  Secondary:   Number of Participants Responding With at Least a 30% Reduction in 24-Hour Worst Back Pain Severity at the 12-Month Endpoint   [ Time Frame: 12 Months ]
  Show Outcome Measure 2

3.  Secondary:   Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 6-Month Endpoint   [ Time Frame: 6 Months ]
  Show Outcome Measure 3

4.  Secondary:   Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 12-Month Endpoint   [ Time Frame: 12 Months ]
  Show Outcome Measure 4

5.  Secondary:   Number of Participants With Time to First Occurrence of at Least 30% Reduction in 24-Hour Worst Back Pain up to 6 Months   [ Time Frame: Days 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, and 300 ]
  Show Outcome Measure 5

6.  Secondary:   Number of Participants With Time to First Occurrence of at Least 30% Reduction in 24-Hour Worst Back Pain up to 12 Months   [ Time Frame: Days 0, 60, 120, 180, 240, 300, 360, 420, 480, 540, and 600 ]
  Show Outcome Measure 6

7.  Secondary:   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 Frame: Days 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, and 300 ]
  Show Outcome Measure 7

8.  Secondary:   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 Frame: Days 0, 60, 120, 180, 240, 300, 360, 420, 480, 540, and 600 ]
  Show Outcome Measure 8

9.  Secondary:   Change From Baseline to 3-Month Endpoint in the Roland-Morris Disability Questionnaire.   [ Time Frame: Baseline, 3 Months ]
  Show Outcome Measure 9

10.  Secondary:   Change From Baseline to 6-Month Endpoint in the Roland-Morris Disability Questionnaire.   [ Time Frame: Baseline, 6 Months ]
  Show Outcome Measure 10

11.  Secondary:   Change From Baseline to 12-Month Endpoint in the Roland-Morris Disability Questionnaire.   [ Time Frame: Baseline, 12 Months ]
  Show Outcome Measure 11

12.  Secondary:   Change From Baseline to 6-Month Endpoint, European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO)   [ Time Frame: Baseline, 6 Months ]
  Show Outcome Measure 12

13.  Secondary:   Change From Baseline to 12-Month Endpoint, European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO)   [ Time Frame: Baseline, 12 Months ]
  Show Outcome Measure 13

14.  Secondary:   Number of Participants With Adverse Events (Safety) During 12 Months   [ Time Frame: Baseline through 12 Months ]
  Show Outcome Measure 14

15.  Secondary:   Number of Participants With Adverse Events (Safety) During 18 Months   [ Time Frame: Baseline through 18 Months ]
  Show Outcome Measure 15

16.  Secondary:   Number of Participants Responding With at Least a 30% Reduction in 24-Hour Worst Back Pain Severity at the 18-Month Endpoint   [ Time Frame: 18 Months ]
  Show Outcome Measure 16

17.  Secondary:   Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 18-Month Endpoint   [ Time Frame: 18 Months ]
  Hide Outcome Measure 17

Measure Type Secondary
Measure Title Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 18-Month Endpoint
Measure Description 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.
Time Frame 18 Months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT). ITT participants were participants who randomized and received at least one dose of the study drug.

Reporting Groups
  Description
Teriparatide Teriparatide 20 micrograms (ug)/day, subcutaneous, 18 months plus once weekly oral placebo
Risedronate Risedronate 35 milligrams (mg)/once weekly, oral, 18 months plus daily subcutaneous injection placebo

Measured Values
    Teriparatide     Risedronate  
Number of Participants Analyzed  
[units: participants]
 		  360     349  
Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 18-Month Endpoint  
[units: participants]
 		   
Responder     260     242  
Non-responder     100     107  


Statistical Analysis 1 for Number of Participants Responding With at Least a 30% Reduction in 24-Hour Average Back Pain Severity at the 18-Month Endpoint
Groups [1] All groups
Method [2] Chi-squared
P Value [3] 0.399
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is for responder versus non-responder.



18.  Secondary:   Number of Participants With Time to First Occurrence of at Least 30% Reduction in 24-Hour Worst Back Pain up to 18 Months   [ Time Frame: Baseline through 18 Months ]
  Show Outcome Measure 18

19.  Secondary:   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 Frame: Baseline through 18 Months ]
  Show Outcome Measure 19

20.  Secondary:   Change From Baseline to 18-Month Endpoint in the Roland-Morris Disability Questionnaire.   [ Time Frame: Baseline, 18 Months ]
  Show Outcome Measure 20

21.  Secondary:   Change From Baseline to 18-Month Endpoint in European Foundation for Osteoporosis Quality of Life Instrument (QUALEFFO)   [ Time Frame: Baseline, 18 Months ]
  Show Outcome Measure 21


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided


Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00343252     History of Changes
Other Study ID Numbers: 9041, B3D-MC-GHCY
Study First Received: June 20, 2006
Results First Received: June 8, 2010
Last Updated: May 20, 2011
Health Authority: United States: Food and Drug Administration