Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children

Recruitment Details

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.

Pre-Assignment Details

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

Reporting Groups

	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

Participant Flow:   Overall Study

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

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.
No text entered.

Reporting Groups

	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
Total	Total of all reporting groups

Baseline Measures

	Placebo Daily	Risedronate Daily	Total
Overall Participants Analyzed  [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
[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.
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.  Primary:

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

2.  Secondary:

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

3.  Secondary:

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

4.  Secondary:

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

5.  Secondary:

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

6.  Secondary:

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

7.  Secondary:

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

8.  Secondary:

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

9.  Secondary:

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

10.  Secondary:

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

11.  Secondary:

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

12.  Secondary:

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

13.  Secondary:

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

14.  Secondary:

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

15.  Secondary:

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

16.  Secondary:

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

17.  Secondary:

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

18.  Secondary:

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

19.  Secondary:

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

20.  Secondary:

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

21.  Secondary:

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

22.  Secondary:

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

23.  Secondary:

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

24.  Secondary:

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

25.  Secondary:

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

26.  Secondary:

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

27.  Secondary:

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

28.  Secondary:

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

29.  Secondary:

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

30.  Secondary:

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

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 ]

32.  Secondary:

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

33.  Secondary:

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

34.  Secondary:

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

35.  Secondary:

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

36.  Secondary:

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

37.  Secondary:

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

38.  Secondary:

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

39.  Secondary:

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

40.  Secondary:

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

41.  Secondary:

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

42.  Secondary:

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

43.  Secondary:

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

44.  Secondary:

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

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.