Postmenopausal Osteoporosis
Conditions
Brief summary
Randomized, multicenter, double-blind, double-dummy, active-controlled, parallel-design study in approximately 201 postmenopausal women. A subset of subjects (approximately 102) will also participate in a pharmacokinetic (PK) component of the study. Each subject will be randomized to 1 of 3 treatment regimens for 3 months.
Interventions
DRUG150 mg
150 mg immediate release (IRBB) risedronate tablet administered orally at least 30 minutes before breakfast.
DRUG75 mg
75 mg delayed release (DRFB) risedronate tablet administered orally immediately after ingesting breakfast
DRUG100 mg
100 mg delayed release (DRFB) risedronate tablet administered orally immediately after ingesting breakfast
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* female, 45 to 80 years of age, in good general health * postmenopausal ≥2 years, surgically or naturally * body mass index less than or equal to 32 kg/m\^2 at screening
Exclusion criteria
* no use within 3 months prior, nor use for more than 1 month at any time within 6 months of: glucocorticoids, anabolic steroids, estrogens, selective estrogen-receptor modulators (SERMs), or estrogen-related drugs, progestins, calcitonin, vitamin D supplements (\>1200 IU per day), calcitriol, calcidiol, or alfacalcidol at any dose, any bisphosphonate. fluoride (≥10 mg/day), strontium (≥50 mg/day), parathyroid hormone, investigational bone active agents. * allergic or abnormal reactions to bisphosphonates * history of cancer within 5 years, excluding squamous and basal cell carcinoma with 6 month remission * positive pregnancy test * no depot injection \>10,000 IU vitamin D in previous 9 months. * no history of GI disease that requires medication, or history of Crohn's disease, ulcerative colitis, diverticular disease, polyps, or surgery that could have changed GI structure or motility. * no history of frequent diarrhea or constipation that requires regular laxative use. * no history of alcohol or durg abuse, hyperparathyroidism, cancer previous 5 years, major surgery within 1 month prior to screening, diabetes, uncontrolled hypertension, cardiovascular, hepatic, renal or GI disease. * no active hyperthyroidism, osteomalacia, use of anticonvulsant medication, or allergic reaction to bisphosphonates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline Serum Type-1 Collagen C-telopeptide (CTX) 75 mg & 100 mg DRFB Tablet Compared With 150 mg IRBB Tablet, Month 4, ITT Population | Month 4 | Fasting serum Bone turn-over marker specimen assayed by electochemiluminescence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | 3 months | — |
| Percent Change From Baseline Urine NTX (Type-1 Collagen Cross-linked N-telopeptide) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | 2 months | Urine NTX Bone turnover marker collected after 8 hour fast, 2nd voided urine between 6-9 am assayed by ELISA. |
| Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | 3 months | ITT Population |
| Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | 2 months | — |
| Serum Bone Specific Alkaline Phosphatase (BAP) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | 2 months | ITT Population |
| Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | 3 months | ITT Population |
| Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | 4 months | ITT Population |
| Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | 4 months | ITT Population |
Countries
United States
Participant flow
Recruitment details
Screening began 27 May 2009
Participants by arm
| Arm | Count |
|---|---|
| 150 mg 150 mg risedronate tablet IRBB (immediate release before breakfast) administered orally at least 30 minutes before breakfast. | 70 |
| 75 mg 75 mg risedronate tablet DRFB (delayed release following breakfast) administered orally immediately after ingesting breakfast | 66 |
| 100 mg 100 mg risedronate tablet DRFB (delayed release following breakfast) administered orally immediately after ingesting breakfast | 69 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | No Study Medication Taken | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 5 |
Baseline characteristics
| Characteristic | 150 mg | 75 mg | 100 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 7.2 | 58.2 years STANDARD_DEVIATION 7.2 | 57.5 years STANDARD_DEVIATION 7 | 58.0 years STANDARD_DEVIATION 7.1 |
| Age, Customized < 65 years | 57 participants | 53 participants | 55 participants | 165 participants |
| Age, Customized 65 years thru <75 years | 10 participants | 12 participants | 13 participants | 35 participants |
| Age, Customized >= 75 years | 2 participants | 1 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Asian (Oriental) | 7 Participants | 6 Participants | 3 Participants | 16 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Caucasian | 60 Participants | 53 Participants | 61 Participants | 174 Participants |
| Race/Ethnicity, Customized Hawaiian/Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Multi-Racial | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Region of Enrollment United States | 70 participants | 66 participants | 69 participants | 205 participants |
| Sex: Female, Male Female | 70 Participants | 66 Participants | 69 Participants | 205 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 50 / 69 | 43 / 66 | 49 / 69 |
| serious Total, serious adverse events | 0 / 69 | 0 / 66 | 0 / 69 |
Outcome results
Primary
Percentage Change From Baseline Serum Type-1 Collagen C-telopeptide (CTX) 75 mg & 100 mg DRFB Tablet Compared With 150 mg IRBB Tablet, Month 4, ITT Population
Fasting serum Bone turn-over marker specimen assayed by electochemiluminescence.
Time frame: Month 4
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Percentage Change From Baseline Serum Type-1 Collagen C-telopeptide (CTX) 75 mg & 100 mg DRFB Tablet Compared With 150 mg IRBB Tablet, Month 4, ITT Population | -41.235 Percent Change from Baseline | Standard Error 2.995 |
| 75 mg | Percentage Change From Baseline Serum Type-1 Collagen C-telopeptide (CTX) 75 mg & 100 mg DRFB Tablet Compared With 150 mg IRBB Tablet, Month 4, ITT Population | -44.832 Percent Change from Baseline | Standard Error 3.012 |
| 100 mg | Percentage Change From Baseline Serum Type-1 Collagen C-telopeptide (CTX) 75 mg & 100 mg DRFB Tablet Compared With 150 mg IRBB Tablet, Month 4, ITT Population | -53.432 Percent Change from Baseline | Standard Error 3.025 |
Comparison: A two group t-test with a 0.100 one-sided significance level would have 96% power to detect the difference between a risedronate 150 mg IRBB mean, µ1, of -46.000 and a risedronate 75 mg DRFB mean, µ2, of -29.900 (a difference in means of -16.100), assuming that the common SD was 28.000, with sample sizes of 60 per group, respectively. Estimates were based on Study 2005107 (35 mg DR once a week Phase 2 study). The sample size calculation was not adjusted for multiplicity.p-value: 0.394690% CI: [-10.568, 3.372]ANOVA
p-value: 0.004590% CI: [-19.208, -5.185]ANOVA
Secondary
Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population
Time frame: 2 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -38.407 Percent Change from Baseline | Standard Error 3.504 |
| 75 mg | Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -33.641 Percent Change from Baseline | Standard Error 3.538 |
| 100 mg | Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -38.625 Percent Change from Baseline | Standard Error 3.547 |
p-value: 0.337290% CI: [-3.421, 12.952]ANOVA
p-value: 0.96590% CI: [-8.427, 7.991]ANOVA
Secondary
Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population
Time frame: 3 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -35.591 Percent Change from Baseline | Standard Error 3.045 |
| 75 mg | Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -35.203 Percent Change from Baseline | Standard Error 3.034 |
| 100 mg | Percent Change From Baseline CTX 150 mg IRBB Tablet Compared With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -46.379 Percent Change from Baseline | Standard Error 3.077 |
p-value: 0.927690% CI: [-6.67, 7.447]ANOVA
p-value: 0.013390% CI: [-17.917, -3.657]ANOVA
Secondary
Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population
ITT Population
Time frame: 3 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -21.673 Percent Change from Baseline | Standard Error 4.351 |
| 75 mg | Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -20.555 Percent Change from Baseline | Standard Error 4.326 |
| 100 mg | Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -29.066 Percent Change from Baseline | Standard Error 4.356 |
p-value: 0.854690% CI: [-8.956, 11.193]ANOVA
p-value: 0.229190% CI: [-17.522, 2.737]ANOVA
Secondary
Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population
ITT Population
Time frame: 4 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | -13.447 Percent Change from Baseline | Standard Error 6.427 |
| 75 mg | Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | -7.942 Percent Change from Baseline | Standard Error 6.464 |
| 100 mg | Percent Change From Baseline Urine NTX Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | -14.360 Percent Change from Baseline | Standard Error 6.492 |
p-value: 0.543690% CI: [-9.452, 20.462]ANOVA
p-value: 0.920190% CI: [-15.959, 14.132]ANOVA
Secondary
Percent Change From Baseline Urine NTX (Type-1 Collagen Cross-linked N-telopeptide) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population
Urine NTX Bone turnover marker collected after 8 hour fast, 2nd voided urine between 6-9 am assayed by ELISA.
Time frame: 2 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Percent Change From Baseline Urine NTX (Type-1 Collagen Cross-linked N-telopeptide) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -15.365 Percent Change from Baseline | Standard Error 6.567 |
| 75 mg | Percent Change From Baseline Urine NTX (Type-1 Collagen Cross-linked N-telopeptide) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -0.837 Percent Change from Baseline | Standard Error 6.631 |
| 100 mg | Percent Change From Baseline Urine NTX (Type-1 Collagen Cross-linked N-telopeptide) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -1.150 Percent Change from Baseline | Standard Error 6.689 |
p-value: 0.119290% CI: [-0.813, 29.868]ANOVA
p-value: 0.129890% CI: [-1.23, 29.659]ANOVA
Secondary
Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population
ITT Population
Time frame: 3 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -17.797 Percent Change from Baseline | Standard Error 3.087 |
| 75 mg | Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -12.831 Percent Change from Baseline | Standard Error 3.075 |
| 100 mg | Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 3, ITT Population | -12.872 Percent Change from Baseline | Standard Error 3.119 |
p-value: 0.252790% CI: [-2.189, 12.12]ANOVA
p-value: 0.261390% CI: [-2.301, 12.153]ANOVA
Secondary
Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population
ITT Population
Time frame: 4 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | -20.885 Percent Change from Baseline | Standard Error 2.956 |
| 75 mg | Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | -19.616 Percent Change from Baseline | Standard Error 2.973 |
| 100 mg | Serum BAP Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 4, ITT Population | -23.710 Percent Change from Baseline | Standard Error 2.986 |
p-value: 0.760690% CI: [-5.609, 8.148]ANOVA
p-value: 0.500690% CI: [-9.744, 4.095]ANOVA
Secondary
Serum Bone Specific Alkaline Phosphatase (BAP) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population
ITT Population
Time frame: 2 months
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg | Serum Bone Specific Alkaline Phosphatase (BAP) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -5.457 Percent Change from Baseline | Standard Error 2.867 |
| 75 mg | Serum Bone Specific Alkaline Phosphatase (BAP) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -2.349 Percent Change from Baseline | Standard Error 2.895 |
| 100 mg | Serum Bone Specific Alkaline Phosphatase (BAP) Comparing Risedronate 150 mg IRBB Tablet With 75 mg & 100 mg DRFB Tablet, Month 2, ITT Population | -0.615 Percent Change from Baseline | Standard Error 2.902 |
p-value: 0.44490% CI: [-3.59, 9.807]ANOVA
p-value: 0.234990% CI: [-1.874, 11.559]ANOVA