A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis.
- Conditions
- Osteoporosis
- Interventions
- Registration Number
- NCT00471237
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a 12 month study designed to evaluate the safety and effectiveness of SB-751689 in the treatment of osteoporosis in post-menopausal women, in comparison with 2 active comparators and placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 564
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alendronate Alendronate All subjects will take calcium (500-660mg elemental daily) and vitamin D (at least 400IU daily) supplements once daily in the evening throughout the study Teriparatide Teriparatide Open-label arm. All subjects will take calcium (500-660mg elemental daily) and vitamin D (at least 400IU daily) supplements once daily in the evening throughout the study Ronacaleret Ronacaleret 4 arms, 100mg, 200mg, 300mg, 400mg. All subjects will take calcium (500-660mg elemental daily) and vitamin D (at least 400IU daily) supplements once daily in the evening throughout the study.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Bone Marrow Density (BMD) at Month 12 Measured by Dual-Energy X-Ray Absorptiometry (DXA) Scans of the Lumbar Spine (L1-L4) Baseline (Day 0) and 12 Months DXA scanners from Hologic and GE Lunar was used to measure BMD by a DXA scan. At least two vertebrae (L1-L4) that were suitable for measurement of BMD were evaluated. The same scanner was used throughout the study for all measurements for a given participant. DXA scans were sent to a central reading facility for quality control and central analysis. Assessments performed on Day 0 were considered as Baseline. Percent change from Baseline was computed as (change from baseline / baseline value) \* 100%. Percent change from Baseline in areal bone mineral density (aBMD) was reported.
Number of Participants Withdrew Due to Hypercalcemia Up to Month 12 A confirmed albumin-adjusted serum calcium pre-dose value of \>11.0 mg/dL or post-dose value of \>12.0 mg/dL was set as a withdrawal criteria for the study. Number of participants who met this pre-defined stopping criteria were reported.
Number of Participants With Hypercalcemia Up to Month 12 Participants with albumin-adjusted serum calcium pre-dose values of \>11.0 mg/ deciliter (dL) or post-dose values of \>12.0 mg/dL were recorded as participants with hypercalcemia. Number of participant with hypercalcemia were reported.
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit Up to 12 Months The potential clinical importance ranges (low and high) of the vital sign parameters-systolic blood pressure (\> 30 millimeter of mercury \[mmHg\] decrease from Baseline, \> 30 mmHg increase from Baseline), diastolic blood pressure (\> 20 mmHg decrease from Baseline and \> 20 mmHg increase from Baseline) and heart rate (\<45 and \>120 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit Up to Month 12 The hematology parameters analyzed were white blood cells (WBC) count with differential WBC count, red blood cells, haemoglobin, haematocrit, mean corpuscular volume and platelet count. The clinical chemistry parameters analyzed were sodium, potassium, calcium, calcium (albumin adjusted), phosphate, bicarbonate, creatinine, bilirubin (total), alanine amino transferase, aspartate amino transferase, glucose, albumin, alkaline phosphatase, creatine phosphokinase, urea, uric acid, total protein, 25-OH vitamin D, 1,25-2(OH) vitamin D, whole parathyroid hormone (PTH 1-84)) and intact PTH (1-84 and 7-84). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important laboratory findings at any visit were reported.
Mean Change From Baseline in Height Baseline (Day 0), Month 6, 12 and early withdrawal Assessments performed on Day 0 were considered as Baseline. Change from Baseline was computed as values at post baseline visit minus Baseline value. Mean change from baseline in height at Month 6 and 12 and early withdrawal were reported.
Mean Change From Baseline in Weight Baseline (Day 0), Month 6, 12 and early withdrawal Baseline values were assessed on Day 0. Change from Baseline was computed as values at post baseline visit minus Baseline value. Mean change from baseline in weight at Month 6, 12 and early withdrawal were reported.
Number of Participant With Electrocardiogram (ECG) Findings Reported as Adverse Event Up to 12 months Full 12-lead ECGs pre-dose at screening and visits 6, 8, 11, 12 and 14 were recorded. Participants rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. The central reviewer measured the following parameters and provide a clinical interpretation: heart rate, RR interval, PR interval, QRS interval, QT (uncorrected) interval, QTcB (Bazett's correction) interval, QTcF (Fridericia's correction) interval. The central reviewer was provided the investigator or designated qualified site physician with a central ECG report or confirmatory report to assist them in identifying any clinically significant abnormalities that would preclude the participant from further participation in the study.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline to Months 6 and 12 in BMD Measured by DXA Scans of the Hip (Total Hip, Femoral Neck and Trochanter). Baseline (Day 0), Month 6 and Month 12 DXA scanners from Hologic and GE Lunar was used to measure BMD by a DXA scan. At least two vertebrae (L1-L4) that were suitable for measurement of BMD were evaluated. The same scanner was used throughout the study for all measurements for a given participant. DXA scans were sent to a central reading facility for quality control and central analysis. Baseline values were assessed on Day 0. Percent Change from Baseline was computed as (change from baseline / baseline value) \* 100%. Percent change from baseline to month 6 and 12 in aBMD of hip (total hip, femoral neck and trochanter) were reported.
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip and Lumbar Spine as Measured by Quantitative Computer Tomography (QCT) Scans Baseline (Day 0) and Month 12 QCT is a three-dimensional non-projectional technique to quantify BMD with a number of advantages to other densitometric techniques. Cortical and trabecular bone can be separated, trabecular volume of interest (VOI) are largely independent of degenerative changes in the spine and 3 dimensional geometric parameters can be determined. BMD as measured by QCT is a true density measured in g/cm\^3 in contrast to DXA Which determines an areal density measured in g/cm\^2. Baseline values were assessed on Day 0. Percent change from Baseline was computed as (change from baseline / baseline value) \* 100%. Percent change from Baseline to month 12 in the volumetric integral, cortical, and trabecular density (BMD) at the hip and lumbar spine measured by QCT were reported.
Percent Change From Baseline to Month 12 in the Total Vertebra Integral VOI at the Lumbar Spine as Measured by QCT Scans Baseline (Day 0) and Month 12 QCT is a three-dimensional non-projectional technique to quantify BMD with a number of advantages to other densitometric techniques. Cortical and trabecular bone can be separated, trabecular VOI are largely independent of degenerative changes in the spine and 3 dimensional geometric parameters can be determined. BMD as measured by QCT is a true density measured in g/cm\^3 in contrast to DXA Which determines an areal density measured in g/cm\^2. Baseline values were assessed on Day 0. Percent change from Baseline was computed as (change from baseline / baseline value) \* 100%.
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans Baseline (Day 0) and Month 12 QCT is a three-dimensional non-projectional technique to quantify BMD with a number of advantages to other densitometric techniques. Cortical and trabecular bone can be separated, trabecular VOI are largely independent of degenerative changes in the spine and 3 dimensional geometric parameters can be determined. BMD as measured by QCT is a true density measured in mg/cm\^3 in contrast to DXA Which determines an areal density measured in g/cm\^2. Baseline values were assessed on Day 0. Percent change from Baseline was computed as (change from baseline / baseline value) \* 100%.
Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans Baseline (Day 0) and Month 12 Percent change in thickness of femur neck cortical VOI thickness and trochanter cortical VOI thickness were at Month 12 measured by QCT were reported. Assessments performed on Day 0 were considered as Baseline. Percent change from Baseline was computed as (change from baseline / baseline value) \* 100%.
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1) Baseline (Day 0), Week 4, Month 3, 6, and 12 Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of CTX1.
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP) Baseline (Day 0), Week 4, Month 3, 6, and 12 Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of P1NP.
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP) Baseline (Day 0), Week 4, Month 3, 6, and 12 Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of BALP.
Blood Concentrations of Ronacaleret Pre-dose (0.0 hour [h]) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12 Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive PK-PD subgroup of participants were analyzed by standard noncompartmental methods. Blood concentrations of ronacaleret were reported.
Percent Change From Baseline to Month 6 in BMD Measured by DXA Scans of the Lumbar Spine (L1-L4) Baseline (Day 0) and Month 6 DXA scanners from Hologic and GE Lunar was used to measure BMD by a DXA scan. At least two vertebrae (L1-L4) that were suitable for measurement of BMD were evaluated. The same scanner was used throughout the study for all measurements for a given participant. DXA scans were sent to a central reading facility for quality control and central analysis. Baseline values were assessed on Day 0. Percent Change from Baseline was computed as (change from baseline / baseline value) \* 100%. Percent change from baseline to month 6 in aBMD was reported.
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline) Baseline (Day 0), Month 5, 6 and 12 Responder rate of participants who remained the same or had any improvement as compared to baseline in DXA BMD of vertebra, femur and vertebra plus femur were reported. Baseline values were assessed on Day 0. Percent change (improvement) from Baseline was computed as (change from baseline / baseline value) \* 100%.
Area Under the Concentration-time Curve Over the Dosing Interval (AUC 0-t) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC 0-tau) of Ronacaleret Pre-dose (0.0 h) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12 Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive pharmacokinetic and pharmacodynamics subgroup of participants were analyzed by standard noncompartmental methods. Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive PK-PD subgroup of participants were analyzed by standard noncompartmental methods. Following log transformation, AUC(0-t) and AUC(0-τ) of ronacaleret were separately analyzed by ANOVA using mixed effects model, fitting treatment and country/region as fixed effects.
Maximum Blood Concentration (Cmax) of Ronacaleret Pre-dose (0.0 h) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12 Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive pharmacokinetic and pharmacodynamics subgroup of participants were analyzed by standard noncompartmental methods. Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive PK-PD subgroup of participants were analyzed by standard noncompartmental methods. Following log transformation, Cmax of ronacaleret were separately analyzed by ANOVA using mixed effects model, fitting treatment and country/region as fixed effects.
Time Required to Achieve Maximum Concentration of Ronacaleret in Blood (Tmax) Pre-dose (0.0 h) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12 Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive pharmacokinetic and pharmacodynamics subgroup of participants were analyzed by standard noncompartmental methods.
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Santiago de Compostela, Spain