Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Osteogenesis Imperfecta
Interventions:	Drug: risedronate sodium (Actonel) Drug: Placebo

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
147 children > or = 4 and < 16 years of age with Osteogenesis Imperfecta (OI) enrolled at 20 North American and international study centers starting 16NOV2004. Patients weighing 10-30 kg received risedronate 2.5 mg or placebo daily and patients weighing more than 30 kg received risedronate 5 mg or placebo daily.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

	Description
Placebo Daily	placebo tablet, once a day for one year then for two years open label risedronate
Risedronate Daily	risedronate tablet, once a day for one year then for two years open label risedronate once a day

	Placebo Daily	Risedronate Daily
STARTED	49 ^[1]	94 ^[2]
Month 12 Completed/Started Open Label	49	87
COMPLETED	43 ^[3]	82 ^[3]
NOT COMPLETED	6	12
Adverse Event	3	2
Protocol Violation	1	1
Withdrawal by Subject	2	8
Lost to Follow-up	0	1

[1]	ITT Population: Patients Randomized and Received at least 1 Dose of Study Drug
[2]	ITT Population: Patients Randomized and Received at least 1 Dose of Study Drug
[3]	Completed Month 36

	Description
Placebo Daily	placebo tablet, once a day for one year then for two years open label risedronate
Risedronate Daily	risedronate tablet, once a day for one year then for two years open label risedronate once a day

	Placebo Daily	Risedronate Daily	Total
Number of Participants [units: participants]	49	94	143
Age ^[1] [units: participants]
<=18 years	49	94	143
Between 18 and 65 years	0	0	0
>=65 years	0	0	0
Age [units: years] Mean ± Standard Deviation	8.6 ± 3.1	8.9 ± 3.4	8.825 ± 3.313
Gender [units: participants]
Female	22	49	71
Male	27	45	72
Region of Enrollment [units: participants]
Australia	8	16	24
Belgium	1	1	2
Chile	4	9	13
Czech Republic	1	4	5
Finland	5	7	12
Germany	5	8	13
Hungary	2	2	4
Italy	1	2	3
Poland	5	9	14
South Africa	0	1	1
Spain	1	1	2
United Kingdom	9	21	30
United States	7	13	20

[1]	There were 147 children enrolled in the study (stated in the protocol). However, 4 children were randomized but did not receive a dose of the study drug. Therefore, only 143 received at least 1 dose of study drug.

Outcome Measures

1. Primary:

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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2. Secondary:

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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3. Secondary:

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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4. Secondary:

Percent Change From Baseline in Total Body BMD at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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5. Secondary:

Percent Change From Baseline in Total Body BMD at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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6. Secondary:

Percent Change From Baseline in Total Body BMD at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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7. Secondary:

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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8. Secondary:

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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9. Secondary:

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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10. Secondary:

Percent Change From Baseline in Total Body BMC at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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11. Secondary:

Percent Change From Baseline in Total Body BMC at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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12. Secondary:

Percent Change From Baseline in Total Body BMC at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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13. Secondary:

Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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14. Secondary:

Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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15. Secondary:

Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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16. Secondary:

Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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17. Secondary:

Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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18. Secondary:

Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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19. Secondary:

Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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20. Secondary:

Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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21. Secondary:

Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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22. Secondary:

Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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23. Secondary:

Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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24. Secondary:

Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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25. Secondary:

New Morphometric Vertebral Fracture at Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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26. Secondary:

New Morphometric Vertebral Fracture at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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27. Secondary:

Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT [ Time Frame: Baseline and Month 12 ]

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28. Secondary:

Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT [ Time Frame: Baseline and Month 36 ]

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29. Secondary:

Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population [ Time Frame: Month 12 ]

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30. Secondary:

Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population [ Time Frame: Month 12 ]

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31. Secondary:

Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population [ Time Frame: Time to First Event (days) up to 12 Months ]

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32. Secondary:

Number of Clinical Fractures, Month 12, ITT Population [ Time Frame: 12 Months ]

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33. Secondary:

Serum BAP - Percent Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and 12 Months ]

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34. Secondary:

Serum BAP - Percent Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and 24 Months ]

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35. Secondary:

Serum BAP - Percent Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and 36 Months ]

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36. Secondary:

Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population [ Time Frame: Baseline and Endpoint / Month 12 ]

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37. Secondary:

Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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38. Secondary:

Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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39. Secondary:

Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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40. Secondary:

Bone Age (Years), Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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41. Secondary:

Bone Age (Years), Change From Baseline to Month 24, ITT Population [ Time Frame: Baseline and Month 24 ]

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42. Secondary:

Bone Age (Years), Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

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43. Secondary:

Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population [ Time Frame: Baseline and Month 12 ]

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44. Secondary:

Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population [ Time Frame: Baseline and Month 36 ]

Show Outcome Measure 44

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:

	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.
	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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The findings of the study may be published in a scientific journal or presented at a scientific meeting. Before submitting the results of the study for publication or presentation, the Investigator will allow the Sponsor 30 days in which to review and comment on the manuscript.

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
The clinical meaningfulness of new fractures in the thoracic spine scored as Genant Grade I is unclear, thus the morphometric vertebral fracture data are evaluated further.

Results Point of Contact:

Name/Title: Grexan Wulff, Manager Regulatory Affairs
Organization: Warner Chilcott
phone: 973-442-3376
e-mail: gwulff@wcrx.com

No publications provided

Responsible Party:	Dietrich Wenderoth, MD, Procter & Gamble
ClinicalTrials.gov Identifier:	NCT00106028 History of Changes
Other Study ID Numbers:	2003100, HMR4003I/3001
Study First Received:	March 18, 2005
Results First Received:	April 15, 2009
Last Updated:	July 27, 2011
Health Authority:	United States: Food and Drug Administration