Study CR9108963: A 12-month, Randomized, Double-blind, Parallel-group, Placebo and Active-controlled Dose-range Finding Study of the Efficacy and Safety of SB-751689 in Post-menopausal Women With Osteoporosis
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- GlaxoSmithKline
- Enrollment
- 564
- Locations
- 1
- Primary Endpoint
- 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)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 79 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: Alendronate (Drug)
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
Intervention: Teriparatide (Drug)
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.
Intervention: Ronacaleret (Drug)
Outcomes
Primary Outcomes
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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans(Baseline (Day 0) and Month 12)
- 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)
- Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)(Baseline (Day 0), Week 4, Month 3, 6, and 12)
- Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)(Baseline (Day 0), Week 4, Month 3, 6, and 12)
- 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)
- 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)
- Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)(Baseline (Day 0), Month 5, 6 and 12)
- 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)
- 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)
- 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)