Osseous Paget's Disease
Conditions
Keywords
Pharmacological theapy
Brief summary
The purpose of this study is to evaluate the safety and efficacy of sodium risedronate tablets administered once daily (one tablet per dose) in patients with osseous Paget's disease for 48 weeks from baseline in daily medical practice.
Detailed description
This special drug use surveillance was designed to evaluate the safety and efficacy of sodium risedronate tablets 17.5 mg administered once daily (one tablet per dose) in patients with osseous Paget's disease in daily medical practice. The usual dosage for adults is 17.5 mg of sodium risedronate administered orally with a sufficient volume (approximately 180 mL) of water once daily after waking for 8 consecutive weeks. For at least 30 minutes after administration, participants should avoid lying in a supine position and taking food, drink (except for water) or other oral drugs.
Interventions
Sodium risedronate tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Osseous Paget's disease patients treated with sodium risedronate tablets 17.5 mg
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had One or More Adverse Drug Reactions | Up to 48 weeks | Adverse drug reaction refers to adverse events related to administered drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Changes From Baseline in Serum ALP Level at Final Assessment Point | Baseline and final assessment point (Up to 48 weeks) | Percentage of changes from baseline in serum ALP level at final assessment point (up to 48 weeks) was reported. |
| Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Baseline and final assessment point (Up to 48 weeks) | Investigators marked severity of pain with a 4-point scale ranging from None to Very Severe (None, Mild, Severe, Very Severe) at baseline and the final assessment point. This scale was specified on the protocol of this observational study. The reported data were number of participants stratified by comparison of pain severity between baseline and final assessment point described as None (at baseline) to Severe (at final assessment point). |
| Number of Participants Stratified by Assessment of Image Findings of Bone Morphogenic Abnormalities at Final Assessment Point Compared With Baseline | Baseline and final assessment point (Up to 48 weeks) | Investigator marked assessment of image findings of bone morphogenic abnormalities at final assessment point compared with baseline as follows; improved, unchanged, worsened. The reported data were the number of participants stratified by assessment of image findings at final assessment point. |
| Number of Participants Stratified by Assessment of Image Findings of Trabecular Bone Structural Abnormalities at Final Assessment Point Compared With Baseline | Baseline and final assessment point (Up to 48 weeks) | Investigator marked assessment of image findings of trabecular bone structural abnormalities at final assessment point compared with baseline as follows; improved, unchanged, worsened. The reported data were the number of participants stratified by assessment of image findings at final assessment point. |
| Percentage of Changes From Baseline in Excess Serum Alkaline Phosphatase (ALP) Level at Final Assessment Point | Baseline and final assessment point (Up to 48 weeks) | Percentage of changes from baseline in excess serum ALP level at final assessment point (up to 48 weeks) was reported. |
| Percentage of Changes From Baseline in Urinary Type 1 Collagen Cross-Linked N-telopeptide (Urinary NTX) Level at Final Assessment Point | Baseline and final assessment point (Up to 48 weeks) | Percentage of changes from baseline in urinary NTX level at final assessment point (up to 48 weeks) was reported. Urinary NTX is one of bone metabolism markers. |
| Percentage of Changes From Baseline in Urinary Deoxypyridinoline (Urinary DPD) Level at Final Assessment Point | Baseline and final assessment point (Up to 48 weeks) | Percentage of changes from baseline in urinary DPD level at final assessment point (up to 48 weeks) was reported. Urinary DPD is one of bone metabolism markers. |
| Percentage of Changes From Baseline in Serum Bone Alkaline Phosphatase (Serum BAP) Level at Final Assessment Point | Baseline and final assessment point (Up to 48 weeks) | Percentage of changes from baseline in serum BAP level at final assessment point (up to 48 weeks) was reported. Serum BAP is one of bone metabolism markers. |
| Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period | Up to 48 weeks | Treatment compliance of this outcome measure refers to the percentage of participants who correctly follow medication. The reported data are percentage of participants in the classification including 4 specific degrees of treatment compliance; 90 % or more; 67 % or more and \<90 %; 25 % or more and \<67 %; less than 25 % or unknown. |
| Number of Participants Stratified by Assessment of Image Findings of Other Abnormalities at Final Assessment Point Compared With Baseline | Baseline and final assessment point (Up to 48 weeks) | Other Abnormalities refer to bone abnormal findings excluding bone morphogenic abnormalities and trabecular bone structural abnormalities (see Outcome Measure 5 and 6). Investigator marked assessment of image findings of other abnormalities at final assessment point compared with baseline as follows; improved, unchanged, worsened. The reported data were the number of participants stratified by assessment of image findings at final assessment point. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 92 investigative sites in Japan, from 01 August 2008 to 24 October 2017.
Pre-assignment details
Participants with a historical diagnosis of osseous Paget's disease were enrolled. Participants received interventions as part of routine medical care.
Participants by arm
| Arm | Count |
|---|---|
| Sodium Risedronate 17.5 mg 17.5 mg of sodium risedronate was administered orally with a sufficient volume (approximately 180 mL) of water once daily after waking for 8 consecutive weeks. Participants received interventions as part of routine medical care. | 307 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case Report Form Uncollected | 6 |
| Overall Study | Protocol Deviation | 2 |
Baseline characteristics
| Characteristic | Sodium Risedronate 17.5 mg | — |
|---|---|---|
| Age, Continuous | 63.2 Years STANDARD_DEVIATION 12.2 | — |
| Classification by Treatment History Initial Treatment | 184 Participants | — |
| Classification by Treatment History Repetitive Treatment | 123 Participants | — |
| Concurrent Medication Had Concurrent Medication | 173 Participants | — |
| Concurrent Medication Had No Concurrent Medication | 134 Participants | — |
| Detailed Diagnosis of Osseous Paget's Disease Monostotic Osseous Paget's Disease | 125 Participants | — |
| Detailed Diagnosis of Osseous Paget's Disease Polyostotic Osseous Paget's Disease | 176 Participants | — |
| Detailed Diagnosis of Osseous Paget's Disease Undifferentiated/Unknown | 6 Participants | — |
| Duration of Diagnosis of Osseous Paget's Disease 1 to < 5 Years | 60 Participants | — |
| Duration of Diagnosis of Osseous Paget's Disease < 1 Year | 106 Participants | — |
| Duration of Diagnosis of Osseous Paget's Disease ≥ 5 Years | 71 Participants | — |
| Duration of Diagnosis of Osseous Paget's Disease Unknown (Not Reported) | 70 Participants | — |
| Experience of Fracture at Disease Site Had Experience | 33 Participants | — |
| Experience of Fracture at Disease Site Had No Experiences | 274 Participants | — |
| Family History of Osseous Paget's Disease Had Family History | 7 Participants | — |
| Family History of Osseous Paget's Disease Had No Family History | 231 Participants | — |
| Family History of Osseous Paget's Disease Unknown | 69 Participants | — |
| Healthcare Category Outpatient | 288 Participants | — |
| Healthcare Category Outpatient and Inpatient | 19 Participants | — |
| Height | 159.49 Centimeters (cm) STANDARD_DEVIATION 9.78 | — |
| Medical Complications Had No Presence of Medical Complications | 105 Participants | — |
| Medical Complications Had Presence of Medical Complications | 202 Participants | — |
| Medical History Had Medical History | 150 Participants | — |
| Medical History Had No Medical History | 156 Participants | — |
| Medical History Unknown | 1 Participants | — |
| Past Drug Therapy for Osseous Paget's Disease Had No Therapies | 92 Participants | — |
| Past Drug Therapy for Osseous Paget's Disease Had Therapy | 209 Participants | — |
| Past Drug Therapy for Osseous Paget's Disease Unknown | 6 Participants | — |
| Predisposition to Hypersensitivity Had No Predisposition to Hypersensitivity | 290 Participants | — |
| Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity | 9 Participants | — |
| Predisposition to Hypersensitivity Unknown | 8 Participants | — |
| Pregnancy Status (not pregnant) | 134 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Japan | 307 Participants | — |
| Sex: Female, Male Female | 134 Participants | — |
| Sex: Female, Male Male | 173 Participants | — |
| Treatment Duration ≤ 56 Days | 145 Participants | — |
| Treatment Duration ≥ 57 Days | 159 Participants | — |
| Treatment Duration Unknown | 3 Participants | — |
| Weight | 59.74 Kilograms (kg) STANDARD_DEVIATION 12.04 | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 307 |
| other Total, other adverse events | 14 / 307 |
| serious Total, serious adverse events | 15 / 307 |
Outcome results
Primary
Percentage of Participants Who Had One or More Adverse Drug Reactions
Adverse drug reaction refers to adverse events related to administered drug.
Time frame: Up to 48 weeks
Population: Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Participants Who Had One or More Adverse Drug Reactions | 14.98 Percentage of Participants |
Secondary
Number of Participants Stratified by Assessment of Image Findings of Bone Morphogenic Abnormalities at Final Assessment Point Compared With Baseline
Investigator marked assessment of image findings of bone morphogenic abnormalities at final assessment point compared with baseline as follows; improved, unchanged, worsened. The reported data were the number of participants stratified by assessment of image findings at final assessment point.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Bone Morphogenic Abnormalities at Final Assessment Point Compared With Baseline | Improved | 7 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Bone Morphogenic Abnormalities at Final Assessment Point Compared With Baseline | Unchanged | 66 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Bone Morphogenic Abnormalities at Final Assessment Point Compared With Baseline | Worsened | 1 Participants |
Secondary
Number of Participants Stratified by Assessment of Image Findings of Other Abnormalities at Final Assessment Point Compared With Baseline
Other Abnormalities refer to bone abnormal findings excluding bone morphogenic abnormalities and trabecular bone structural abnormalities (see Outcome Measure 5 and 6). Investigator marked assessment of image findings of other abnormalities at final assessment point compared with baseline as follows; improved, unchanged, worsened. The reported data were the number of participants stratified by assessment of image findings at final assessment point.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Other Abnormalities at Final Assessment Point Compared With Baseline | Improved | 6 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Other Abnormalities at Final Assessment Point Compared With Baseline | Unchanged | 31 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Other Abnormalities at Final Assessment Point Compared With Baseline | Worsened | 2 Participants |
Secondary
Number of Participants Stratified by Assessment of Image Findings of Trabecular Bone Structural Abnormalities at Final Assessment Point Compared With Baseline
Investigator marked assessment of image findings of trabecular bone structural abnormalities at final assessment point compared with baseline as follows; improved, unchanged, worsened. The reported data were the number of participants stratified by assessment of image findings at final assessment point.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Trabecular Bone Structural Abnormalities at Final Assessment Point Compared With Baseline | Improved | 14 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Trabecular Bone Structural Abnormalities at Final Assessment Point Compared With Baseline | Unchanged | 57 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Assessment of Image Findings of Trabecular Bone Structural Abnormalities at Final Assessment Point Compared With Baseline | Worsened | 1 Participants |
Secondary
Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point
Investigators marked severity of pain with a 4-point scale ranging from None to Very Severe (None, Mild, Severe, Very Severe) at baseline and the final assessment point. This scale was specified on the protocol of this observational study. The reported data were number of participants stratified by comparison of pain severity between baseline and final assessment point described as None (at baseline) to Severe (at final assessment point).
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | None to None | 138 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | None to Mild | 1 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | None to Severe | 1 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Mild to None | 12 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Mild to Mild | 14 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Severe to None | 18 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Severe to Mild | 21 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Severe to Severe | 39 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Severe to Very Severe | 1 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Very Severe to None | 6 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Very Severe to Mild | 2 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Very Severe to Severe | 4 Participants |
| Sodium Risedronate 17.5 mg | Number of Participants Stratified by Comparison of Pain Scale Associated With Osseous Paget's Disease Between Baseline and Final Assessment Point | Very Severe to Very Severe | 1 Participants |
Secondary
Percentage of Changes From Baseline in Excess Serum Alkaline Phosphatase (ALP) Level at Final Assessment Point
Percentage of changes from baseline in excess serum ALP level at final assessment point (up to 48 weeks) was reported.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Changes From Baseline in Excess Serum Alkaline Phosphatase (ALP) Level at Final Assessment Point | -72.47 Percentage of change | Standard Deviation 125.78 |
Secondary
Percentage of Changes From Baseline in Serum ALP Level at Final Assessment Point
Percentage of changes from baseline in serum ALP level at final assessment point (up to 48 weeks) was reported.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Changes From Baseline in Serum ALP Level at Final Assessment Point | -31.71 Percentage of change | Standard Deviation 30.47 |
Secondary
Percentage of Changes From Baseline in Serum Bone Alkaline Phosphatase (Serum BAP) Level at Final Assessment Point
Percentage of changes from baseline in serum BAP level at final assessment point (up to 48 weeks) was reported. Serum BAP is one of bone metabolism markers.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Changes From Baseline in Serum Bone Alkaline Phosphatase (Serum BAP) Level at Final Assessment Point | -43.57 Percentage of change | Standard Deviation 33.13 |
Secondary
Percentage of Changes From Baseline in Urinary Deoxypyridinoline (Urinary DPD) Level at Final Assessment Point
Percentage of changes from baseline in urinary DPD level at final assessment point (up to 48 weeks) was reported. Urinary DPD is one of bone metabolism markers.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Changes From Baseline in Urinary Deoxypyridinoline (Urinary DPD) Level at Final Assessment Point | -10.01 Percentage of change | Standard Deviation 60.23 |
Secondary
Percentage of Changes From Baseline in Urinary Type 1 Collagen Cross-Linked N-telopeptide (Urinary NTX) Level at Final Assessment Point
Percentage of changes from baseline in urinary NTX level at final assessment point (up to 48 weeks) was reported. Urinary NTX is one of bone metabolism markers.
Time frame: Baseline and final assessment point (Up to 48 weeks)
Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The number analyzed is the number of participants with data available for analysis at the given time-point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Changes From Baseline in Urinary Type 1 Collagen Cross-Linked N-telopeptide (Urinary NTX) Level at Final Assessment Point | -51.01 Percentage of change | Standard Deviation 34.43 |
Secondary
Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period
Treatment compliance of this outcome measure refers to the percentage of participants who correctly follow medication. The reported data are percentage of participants in the classification including 4 specific degrees of treatment compliance; 90 % or more; 67 % or more and \<90 %; 25 % or more and \<67 %; less than 25 % or unknown.
Time frame: Up to 48 weeks
Population: Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sodium Risedronate 17.5 mg | Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period | 90 % or More | 95.11 Percentage of participants |
| Sodium Risedronate 17.5 mg | Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period | 67 % or More and <90 % | 2.61 Percentage of participants |
| Sodium Risedronate 17.5 mg | Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period | 25 % or More and <67 % | 0.65 Percentage of participants |
| Sodium Risedronate 17.5 mg | Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period | Less than 25 % | 0.33 Percentage of participants |
| Sodium Risedronate 17.5 mg | Percentage of Participants Stratified by Treatment Compliance (Medicine Adherence) During Treatment Period | Unknown | 1.30 Percentage of participants |